ORCID Profile
0000-0002-7039-6325
Current Organisation
Monash University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Psychology | Developmental Psychology and Ageing | Social and Community Psychology
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Psychology and Cognitive Sciences |
Publisher: Elsevier BV
Date: 2022
Publisher: Oxford University Press (OUP)
Date: 24-02-2015
DOI: 10.1093/IJE/DYU273
Abstract: Several broad lines of evidence support the involvement of epigenetic processes in neurodevelopment and psychiatric disorders. Epigenetic disruption also provides a potential mechanism to account for the numerous gene-environment interactions that have been reported in association with neuropsychiatric phenotypes. A review of the literature was performed with keywords 'depression', 'depressive disorder' or 'antidepressants' and 'DNA methylation', or 'epigenetics' in humans. Citations were limited to those written in English and published prior to July 2014. We present a summary of results to date. Most studies have focused on DNA methylation in various CNS or peripheral tissue, with almost universally small s le sizes. Although seven epigenome-wide association studies have now been reported, the majority of studies have used a candidate-gene approach. Three genes (SLC6A4, BDNF, NR3C1) have been investigated in more than one study, but replication of findings is generally lacking. Recent evidence provides insights to epigenetic processes in psychiatric disorders however, replication is lacking and care must be taken in the interpretation of current findings. This applies to epigenetic epidemiology generally, which is subject to various limitations that no single approach can address in isolation. Due to limited focus of most depression studies to date, placing the findings within the broader context of mood disorder pathophysiology may prove challenging. However, identifying peripheral biomarkers for depressive disorder remains a tantalising possibility, especially given the potential for carefully-designed longitudinal studies with multiple biospecimens and ongoing advances in epigenetic technologies.
Publisher: Royal College of Psychiatrists
Date: 2008
DOI: 10.1192/BJP.BP.107.039164
Abstract: Depression may increase the risk of mortality among certain subgroups of older people, but the part played by antidepressants in this association has not been thoroughly explored. To identify the characteristics of older populations who are most at risk of dying, as a function of depressive symptoms, gender and antidepressant use. Adjusted Cox proportional hazards models were used to determine the association between depression and/or antidepressant use and 4-year survival of 7363 community-dwelling elderly people. Major depressive disorder was evaluated using a standardised psychiatric examination based on DSM-IV criteria and depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale. Depressed men using antidepressants had the greatest risk of dying, with increasing depression severity corresponding to a higher hazard risk. Among women, only severe depression in the absence of treatment was significantly associated with mortality. The association between depression and mortality is gender-dependent and varies according to symptom load and antidepressant use.
Publisher: Wiley
Date: 2021
DOI: 10.1002/DAD2.12180
Abstract: This study aimed to investigate cognitive aging trajectories, the associated sociodemographic characteristics, and the association of these trajectories with dementia. Generally healthy older adults (n = 19,114) were followed for up to 7 years, with regular cognitive assessments. Group‐based trajectory modeling identified distinct cognitive trajectories. Four to seven trajectories were identified per cognitive domain. Stable trajectories were observed across domains. Improvement in verbal fluency and minor psychomotor slowing were common. Substantial decline in global cognition and episodic memory were observed in a small proportion of in iduals. Older, less educated participants and men were more common in lower‐functioning trajectories ( p .001). The highest proportions of dementia cases were in trajectories with major decline in global cognition (56.9%) and memory (33.2%). Inter‐in idual variability in cognitive trajectories was observed across all domains. Some in iduals appear resilient to cognitive decline even with advancing age. Further research into factors promoting cognitive resilience is needed.
Publisher: Future Medicine Ltd
Date: 31-10-2023
Publisher: The Science Breaker
Date: 19-05-2016
Publisher: Oxford University Press (OUP)
Date: 17-04-2019
Abstract: DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an in idual’s chronological age and can predict their risk of age-related disease and mortality. This study reviewed the evidence that environmental, lifestyle and health factors are associated with the Horvath and Hannum epigenetic clocks. A systematic search identified 61 studies. Chronological age was correlated with DNAm age in blood (median .83, range .13–.99). In a meta-analysis body mass index (BMI) was associated with increased DNAm age (Hannum β: 0.07, 95% CI 0.04 to 0.10 Horvath β: 0.06, 95% CI 0.02 to 0.10), but there was no association with smoking (Hannum β: 0.12, 95% CI −0.50 to 0.73 Horvath β:0.18, 95% CI −0.10 to 0.46). DNAm age was positively associated with frailty (three studies, n = 3,093), and education was negatively associated with the Hannum estimate of DNAm age specifically (four studies, n = 13,955). For most other exposures, findings were too inconsistent to draw conclusions. In conclusion, BMI was positively associated with biological aging measured using DNAm, with some evidence that frailty also increased aging. More research is needed to provide conclusive evidence regarding other exposures. This field of research has the potential to provide further insights into how to promote slower biological aging and ultimately prolong healthy life.
Publisher: Informa UK Limited
Date: 09-10-2018
DOI: 10.1080/10253890.2018.1519019
Abstract: A recent study reported for the first time, that DNA methylation of the KITLG gene mediates the association between childhood trauma and cortisol stress reactivity. Our study aimed to provide the first independent replication of these findings. ESPRIT is a prospective study of community-dwelling participants (age ≥ 65), randomly selected from the electoral rolls of the Montpellier district, in France. Clinical depression was assessed using the Mini-International Neuropsychiatric Interview (MINI, French version 5.00), and the Centre for Epidemiological Studies Depression Scale (CES-D). Experiences of childhood adversity were ascertained via a 25-item questionnaire. Morning, evening, and diurnal salivary cortisol was measured under basal and stress conditions and determined using direct radioimmunoassay analysis. DNA methylation of the KITLG gene was quantified in whole blood using the SEQUENOM MassARRAY EpiTYPER platform. A significant negative association was observed between KITLG DNA methylation and both morning cortisol (β = -1.846 ± 0.666, p = .007) and diurnal cortisol (area under curve [AUC]) (β = -19.429 ± 8.868, p = .031) under a stress condition. However, only the former association was significant after correcting for multiple testing. Further, this association remained after adjusting for age, sex, and depression status. No significant association was observed between childhood trauma and KITLG DNA methylation in this older population. This study provides support for an association between KITLG methylation and stress cortisol levels, suggesting that DNA methylation of this gene may play a role in the longer term regulation of the stress system. Lay summary The significant negative association between KITLG DNA methylation and morning cortisol, measured under a stressful condition, suggests that in iduals with higher KITLG methylation will secrete lower levels of cortisol whilst under stress.
Publisher: Wiley
Date: 2021
DOI: 10.1002/DAD2.12226
Abstract: Diversity in cognition among apolipoprotein E ( APOE ) ε4 homozygotes can range from early‐onset Alzheimer's disease (AD) to a lifetime with no symptoms. We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy APOE ε4 homozygotes aged ≥75 years (n = 213) and early‐onset APOE ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this ersity. The PRS for AD was significantly higher in APOE ε4 homozygote AD cases compared to older cognitively healthy APOE ε4/ε4 controls (odds ratio [OR] 8.39 confidence interval [CI] 2.0–35.2 P = .003). The difference in the same PRS between APOE ε3/ε3 extremes was not as significant (OR 3.13 CI 0.98–9.92 P = .053) despite similar numbers and power. There was no statistical difference in an educational attainment PRS between these age extreme case‐controls. A PRS for AD contributes to modified cognitive expression of the APOE ε4/ε4 genotype at phenotypic extremes of risk.
Publisher: Informa UK Limited
Date: 27-04-2017
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: Springer Science and Business Media LLC
Date: 29-03-2016
DOI: 10.1038/TP.2016.32
Abstract: Compelling evidence suggests that maternal mental health in pregnancy can influence fetal development. The imprinted genes, insulin-like growth factor 2 ( IGF2 ) and H19, are involved in fetal growth and each is regulated by DNA methylation. This study aimed to determine the association between maternal mental well-being during pregnancy and differentially methylated regions (DMRs) of IGF2 (DMR0) and the IGF2/H19 imprinting control region (ICR) in newborn offspring. Maternal depression, anxiety and perceived stress were assessed at 28 weeks of pregnancy in the Barwon Infant Study ( n =576). DNA methylation was measured in purified cord blood mononuclear cells using the Sequenom MassArray Platform. Maternal anxiety was associated with a decrease in average ICR methylation (Δ=−2.23% 95% CI=−3.68 to −0.77%), and across all six of the in idual CpG units in anxious compared with non-anxious groups. Birth weight and sex modified the association between prenatal anxiety and infant methylation. When stratified into lower (⩽3530 g) and higher ( g) birth weight groups using the median birth weight, there was a stronger association between anxiety and ICR methylation in the lower birth weight group (Δ=−3.89% 95% CI=−6.06 to −1.72%), with no association in the higher birth weight group. When stratified by infant sex, there was a stronger association in female infants (Δ=−3.70% 95% CI=−5.90 to −1.51%) and no association in males. All the linear regression models were adjusted for maternal age, smoking and folate intake. These findings show that maternal anxiety in pregnancy is associated with decreased IGF2 / H19 ICR DNA methylation in progeny at birth, particularly in female, low birth weight neonates. ICR methylation may help link poor maternal mental health and adverse birth outcomes, but further investigation is needed.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-10-2023
Publisher: MDPI AG
Date: 13-02-2023
Abstract: Background: Optimism is a disposition characterised by positive future expectancies, while pessimism is characterised by expecting the worst. High optimism and low pessimism promote the health of older adults and may potentiate full engagement in life. We identified socioeconomic, behavioural, and social factors associated with optimism and pessimism in older adults. Methods: Participants included 10,146 community-dwelling, apparently healthy Australian adults aged 70 years and over from the ASPREE Longitudinal Study of Older Persons (ALSOP). Optimism and pessimism were measured using the revised Life Orientation Test. Cross-sectional ordinal logistic regression was used to determine the socioeconomic, behavioural, and social health factors associated with optimism and pessimism. Results: Higher education, greater physical activity, lower loneliness, and volunteering were associated with higher optimism and lower pessimism. Low social support was associated with higher pessimism. Higher socioeconomic advantage, greater income, and living alone were associated with lower pessimism. Women were more optimistic and less pessimistic than men. The association of age, smoking status, and alcohol consumption with optimism and pessimism differed for men and women. Conclusions: Factors associated with higher optimism and lower pessimism were also those demonstrated to support healthy ageing. Health-promotion action at the in idual level (e.g., smoking cessation or regular physical activity), health professional level (e.g., social prescribing or improving access and quality of care for all older adults), and community level (e.g., opportunities for volunteer work or low-cost social activities for older adults) may improve optimism and reduce pessimism, possibly also promoting healthy ageing.
Publisher: Informa UK Limited
Date: 22-07-2019
DOI: 10.1080/10408363.2019.1639129
Abstract: Dementia is an overarching term which describes a group of symptoms that result in long-term decline in cognitive functioning that is significant enough to affect daily function. It is caused by a number of different diseases, the most common of which is Alzheimer's disease. Currently, there are no definitive biomarkers for preclinical or diagnostic use, or which differentiate between underlying disease types. The purpose of this review is to highlight several important areas of research on blood-based biomarkers of dementia, with a specific focus on epigenetic biomarkers. A systematic search of the literature identified 77 studies that compared blood DNA methylation between in iduals with dementia and controls and 45 studies that measured microRNA. Very few studies were identified that focused on histone modifications. There were many promising findings from studies in the field of blood-based epigenetic biomarkers of dementia, however, a lack of consistency in study design, technologies, and platforms used for the biomarker measurement, as well as statistical analysis methods, have h ered progress. To date, there are very few findings that have been independently replicated across more than one study, indicating a preponderance of false-positive findings and the field has likely been plagued by positive publication bias. Here, we highlight and discuss several of the limitations of existing studies and provide recommendations for how these could be overcome in future research. A robust framework should be followed to enable development of the most valid and reproducible biomarkers with the strongest clinical utility. Defining a series of biomarkers that may be complimentary to each other could permit a stronger multifactorial biomarker to be developed that would allow for not only accurate dementia diagnosis but preclinical detection.
Publisher: Elsevier BV
Date: 07-2020
Publisher: SAGE Publications, Inc.
Date: 2017
Publisher: Cold Spring Harbor Laboratory
Date: 14-09-2023
Publisher: Wiley
Date: 10-07-2017
DOI: 10.1002/ERV.2530
Publisher: Future Medicine Ltd
Date: 09-2022
Abstract: Background: Biological aging may be a robust biomarker of dementia or cognitive performance. This systematic review synthesized the evidence for an association between epigenetic aging and dementia, mild cognitive impairment and cognitive function. Methods: A systematic search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: 30 eligible articles were included. There was no strong evidence that accelerated epigenetic aging was associated with dementia/mild cognitive impairment (n = 7). There was some evidence of an association with poorer cognition (n = 20), particularly with GrimAge acceleration, but this was inconsistent and varied across cognitive domains. A meta-analysis was not performed due to high study heterogeneity. Conclusion: There is insufficient evidence to indicate that current epigenetic aging clocks can be clinically useful biomarkers of dementia or cognitive aging.
Publisher: Oxford University Press (OUP)
Date: 26-12-2020
Abstract: Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin’s effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults. The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo death without prior disability was a competing risk. Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66–1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12). Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability.
Publisher: SAGE Publications
Date: 21-04-2019
Publisher: S. Karger AG
Date: 2022
DOI: 10.1159/000522040
Abstract: b i Objectives: /i /b The objectives of this study were to examine whether weight loss, weight status (based on body mass index [BMI] categories), and abdominal obesity (based on waist circumference [WC]) were associated with a 17-year mortality risk in community-dwelling older adults. b i Methods: /i /b Participants were 2,017 community-dwelling adults aged 65 years or above in the longitudinal Enquête de Santé Psychologique-Risques, Incidence et Traitement study. Self-reported weight loss was collected at baseline during face-to-face interviews. Bodyweight (kg), height (m), and WC (cm) were independently measured at the baseline. BMI was categorized as follows: underweight (BMI & #x3c .5 kg/m sup /sup ), normal weight (18.5–24.9 kg/m sup /sup ), overweight (25–29.9 kg/m sup /sup ), and obese (≥30 kg/m sup /sup ). Abdominal obesity was defined by a WC of ≥102 cm in men and ≥88 cm in women. Adjusted Cox proportional hazards models were used to examine associations of weight loss, weight status, and abdominal obesity with all-cause mortality. b i Results: /i /b Over 17 years of follow-up (median 15.5 years), 812 participants died. Abdominal obesity compared to nonabdominal obesity was associated with a 49% increased mortality risk (95% confidence interval (CI): 1.22–1.83). However, being overweight (but not obese) was associated with a 20% decreased risk (95% CI: 0.66–0.97) compared to a normal BMI. Gender did not affect these associations. In the whole cohort, self-reported weight loss at baseline was not associated with an increased mortality risk after adjusting for health and lifestyle factors. However, in men, a baseline self-reported recent weight loss of & #x3e kg was associated with a 52% increase in mortality risk (95% CI: 1.05–2.18) in a fully adjusted model. b i Conclusion: /i /b In community-dwelling adults aged ≥65 years, abdominal obesity was strongly associated with increased mortality risk. Being overweight appeared, however, to be protective against mortality. Modest self-reported weight loss was not associated with all-cause mortality in community-dwelling older adults after adjusting for health and lifestyle factors. However, men reporting recent weight loss of more than 3 kg may be at increased risk. The findings of this study support the use of WC, rather than BMI, as a predictor of mortality risk in older adults.
Publisher: Royal College of Psychiatrists
Date: 08-2011
DOI: 10.1192/BJP.BP.111.091751
Abstract: Evidence suggests a role for oestrogen in depression but the involvement of oestrogen receptor polymorphisms remains unknown. To determine the association between oestrogen receptor polymorphisms and late-life depression and the modifying effect of hormone treatment. Depression was assessed using the Mini-International Neuropsychiatric Interview, according to DSM-IV criteria and the Centre for Epidemiologic Studies – Depression Scale. The association between oestrogen receptor α and β (ER-α and ER-β) polymorphisms with severe depression was examined in 6017 community-dwelling elderly people using multivariate logistic regression. In women, the ER-α rs2234693 and rs9340799 polymorphisms were significantly associated with the risk of late-life depression. The A allele of ER-β rs1256049 increased the risk of depression, but only for non-current users of hormone treatment. In men, only the ER-β rs4986938 polymorphism showed a weak association with depression risk. Oestrogen receptor polymorphisms are associated with severe late-life depression risk in women only.
Publisher: Springer Science and Business Media LLC
Date: 04-09-2018
Publisher: Informa UK Limited
Date: 26-02-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-03-2022
Abstract: Mild albuminuria was associated with worse baseline cognitive function, cognitive decline, and increased risk for incident dementia. Screening cognitive tests for older persons with a urine albumin-creatinine ratio ≥3 mg/mmol could identify those at elevated risk of cognitive decline and dementia. CKD is a risk factor for cognitive impairment (CI), but reports of in idual associations of eGFR and albuminuria with CI and incident dementia in healthier, older, longitudinal populations are lacking. Our goal was to estimate these associations in a large cohort of older healthy persons. In a longitudinal cohort study of older persons without prior cardiovascular disease, we estimated the associations between baseline eGFR (in ml/min per 1.73 m 2 ) and albuminuria, measured as urine albumin-creatinine ratio (UACR in mg/mmol) and cognitive test scores, declines in cognitive test scores, and incident dementia using adjusted linear and linear mixed models. Cox proportional hazards regression models assessed the association between baseline kidney function and incident CI no dementia (CIND) or dementia at a median of 4.7 years. At baseline, among 18,131 participants, median age was 74 years, eGFR was 74 (IQR, 63–84) ml/min per 1.73 m 2 , UACR was 0.8 (IQR, 0.5–1.5) mg/mmol (7.1 [4.4–13.3] mg/g), and 56% were female. Baseline eGFR was not associated with performance on any cognitive tests in cross-sectional analysis, nor was incident CIND or dementia over a median follow-up of 4.7 years. However, baseline UACR ≥3 mg/mmol (≥26.6 mg/g) was significantly associated with lower baseline scores and larger declines on the Modified Mini-Mental State Exam, verbal memory and processing speed tests, and with incident CIND (hazard ratio [HR], 1.19 95% CI, 1.07 to 1.33) and dementia (HR, 1.32 95% CI, 1.06 to 1.66). Mild albuminuria was associated with worse baseline cognitive function, cognitive decline, and increased risk for incident CIND and dementia. Screening global cognitive tests for older persons with UACR ≥ 3 mg/mmol could identify those at elevated risk of cognitive decline and dementia.
Publisher: Cambridge University Press (CUP)
Date: 10-04-2019
DOI: 10.1017/S0033291719000709
Abstract: Maternal mental health during pregnancy and postpartum predicts later emotional and behavioural problems in children. Even though most perinatal mental health problems begin before pregnancy, the consequences of preconception maternal mental health for children's early emotional development have not been prospectively studied. We used data from two prospective Australian intergenerational cohorts, with 756 women assessed repeatedly for mental health problems before pregnancy between age 13 and 29 years, and during pregnancy and at 1 year postpartum for 1231 subsequent pregnancies. Offspring infant emotional reactivity, an early indicator of differential sensitivity denoting increased risk of emotional problems under adversity, was assessed at 1 year postpartum. Thirty-seven percent of infants born to mothers with persistent preconception mental health problems were categorised as high in emotional reactivity, compared to 23% born to mothers without preconception history (adjusted OR 2.1, 95% CI 1.4–3.1). Ante- and postnatal maternal depressive symptoms were similarly associated with infant emotional reactivity, but these perinatal associations reduced somewhat after adjustment for prior exposure. Causal mediation analysis further showed that 88% of the preconception risk was a direct effect, not mediated by perinatal exposure. Maternal preconception mental health problems predict infant emotional reactivity, independently of maternal perinatal mental health while associations between perinatal depressive symptoms and infant reactivity are partially explained by prior exposure. Findings suggest that processes shaping early vulnerability for later mental disorders arise well before conception. There is an emerging case for expanding developmental theories and trialling preventive interventions in the years before pregnancy.
Publisher: American Society for Cell Biology (ASCB)
Date: 12-2006
Abstract: The Ire1p transmembrane receptor kinase/endonuclease transduces the unfolded protein response (UPR) from the endoplasmic reticulum (ER) to the nucleus in Saccharomyces cerevisiae. In this study, we analyzed the capacity of a highly basic sequence in the linker region of Ire1p to function as a nuclear localization sequence (NLS) both in vivo and in vitro. This 18-residue sequence is capable of targeting green fluorescent protein to the nucleus of yeast cells in a process requiring proteins involved in the Ran GTPase cycle that facilitates nuclear import. Mutagenic analysis and importin binding studies demonstrate that the Ire1p linker region contains overlapping potential NLSs: at least one classical NLS (within sequences 642 KKKRKR 647 and/or 653 KKGR 656 ) that is recognized by yeast importin α (Kap60p) and a novel βNLS ( 646 KRGSRGGKKGRK 657 ) that is recognized by several yeast importin β homologues. Kinetic binding data suggest that binding to importin β proteins would predominate in vivo. The UPR, and in particular ER stress-induced HAC1 mRNA splicing, is inhibited by point mutations in the Ire1p NLS that inhibit nuclear localization and also requires functional RanGAP and Ran GEF proteins. The NLS-dependent nuclear localization of Ire1p would thus seem to be central to its role in UPR signaling.
Publisher: SAGE Publications
Date: 11-04-2022
DOI: 10.1177/08982643221083118
Abstract: Objective: Positive psychosocial factors may protect against cardiovascular disease (CVD). We aimed to determine the association of optimism and pessimism with CVD events in community-dwelling older adults. Methods: 11,651 adults aged 70 years and over, participants of the ASPREE Longitudinal Study of Older Persons (ALSOP), were followed-up for 4.7 years (median). The association of optimism and pessimism (assessed as separate constructs by revised Life Orientation Test) and incident CVD events (composite and components) was assessed by Cox regression adjusted for demographic, socioeconomic and health factors. Results: No association was observed between optimism and pessimism with composite CVD events. Being more pessimistic was associated with a greater risk of fatal coronary heart disease, while being more optimistic was associated with a lower risk of non-fatal myocardial infarction. Conclusions: Optimism and pessimism may shape cardiovascular health of older adults and we argue these psychosocial factors should be researched as separate constructs.
Publisher: Springer Science and Business Media LLC
Date: 29-05-2018
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.ATHEROSCLEROSIS.2012.05.009
Abstract: An inverse correlation between plasma testosterone levels and carotid intima-media thickness (IMT) has been reported in men. We investigated whether this association could be mediated or modified by traditional cardiovascular risk factors as well as inflammatory status. In the Three-City population-based cohort study, 354 men aged 65 and over had available baseline data on hormones levels and carotid ultrasonography. Plasma concentrations of testosterone (total and bioavailable), estradiol and sex hormone-binding globulin (SHBG), together with cardiovascular risk factors were measured. IMT in plaque-free site and atherosclerotic plaques in the extracranial carotid arteries were determined using a standardized protocol. Multiple linear regression models were used to analyze this association and interaction study. Analyses with and without adjustment for cardiovascular risk factors showed that carotid IMT was inversely and significantly correlated with total and bioavailable testosterone levels but not with SHBG and estradiol levels. This association depended on C-reactive protein (CRP) levels (p for interaction 3.2 ng/mL (0.76 mm and 0.70 mm respectively, p < 0.01). By contrast, among men with CRP ≤ 2 mg/L, mean IMT was similar in both groups (0.72 mm and 0.71 mm respectively, p = 0.77). Similar results were found for total testosterone although not significant. No association was found between plasma hormones levels and atherosclerotic plaques. In elderly men, low plasma testosterone is associated with elevated carotid intima-media thickness only in those with low-grade inflammation. Traditional risk factors have no mediator role.
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S12877-021-02602-2
Abstract: Poor social health is associated with increased risk of cardiovascular disease (CVD). Recent research suggests that different social health domains should be considered separately as the implications for health and possible interventions may differ. To assess social isolation, low social support and loneliness as predictors of CVD. Secondary analysis of 11,486 community-dwelling, Australians, aged 70 years and over, free of CVD, dementia, or significant physical disability, from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Social isolation, social support (Revised Lubben Social Network Scale), and loneliness were assessed as predictors of CVD using Cox proportional-hazard regression. CVD events included fatal CVD, heart failure hospitalization, myocardial infarction and stroke. Analyses were adjusted for established CVD risk factors. In iduals with poor social health were 42 % more likely to develop CVD (p = 0.01) and twice as likely to die from CVD (p = 0.02) over a median 4.5 years follow-up. Interaction effects indicated that poorer social health more strongly predicted CVD in smokers (HR 4.83, p = 0.001, p-interaction = 0.01), major city dwellers (HR 1.94, p 0.001, p-interaction=0.03), and younger older adults (70-75 years HR 2.12, p 0.001, p-interaction = 0.01). Social isolation (HR 1.66, p = 0.04) and low social support (HR 2.05, p = 0.002), but not loneliness (HR 1.4, p = 0.1), predicted incident CVD. All measures of poor social health predicted ischemic stroke (HR 1.73 to 3.16). Among healthy older adults, social isolation and low social support may be more important than loneliness as cardiovascular risk factors. Social health domains should be considered in future CVD risk prediction models.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2017
DOI: 10.1007/S11673-017-9817-6
Abstract: The overarching issue with this case study is poor regulation and quality control over direct-to-consumer genetic testing, delivered in the absence of any medical oversight.
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.PSYNEUEN.2008.09.008
Abstract: While recent studies suggest that exogenous estrogen treatment could help reduce age-related cognitive decline and delay the onset of dementia, this has not been found consistently. Few studies have considered the influence of life-time estrogen exposure which may have an independent effect on cognition and/or modulate treatment response. The aim of this study was to examine whether factors related to estrogen exposure across the life-time were associated with cognitive function in postmenopausal women. A battery of cognitive tests were administered at baseline and at 2 and 4 years of follow-up to evaluate cognitive performance among a population-based cohort of 996 French women aged 65 years or older, who were recruited as part of the ESPRIT study. Detailed reproductive histories were also obtained. Logistic regression models, controlling for an extensive range of potential confounding factors, were generated to determine whether hormone-related factors across a woman's lifetime were associated with poor cognitive performance in later life. Age at first menses was negatively associated with performance on the tasks of visual memory and psychomotor speed, while a longer reproductive period was associated with better verbal fluency. Likewise, women who had their first child at a young age performed significantly worse on each of these tasks, as well as on a measure of global cognitive function. The results also suggest that current hormone therapy may be beneficial for a number of cognitive domains, however, in multivariate analysis, women performed significantly better on the task of visual memory only. In contrast, in analysis adjusted for baseline cognitive performance and a range of other factors, none of the reproductive variables were associated with a decline in cognitive performance or the incidence of dementia during the 4-year follow-up period. In addition to hormone therapy, certain hormone-related events across the lifetime are also associated with cognitive functioning in later life. They were not observed in this study to modulate dementia risk however, this should be verified over a longer follow-up period. Further studies will also be required to determine whether lifetime hormonal exposure may modify women's response to hormone therapy after the menopause.
Publisher: Springer Science and Business Media LLC
Date: 20-01-2015
DOI: 10.1038/TP.2014.145
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.BRAINRES.2010.10.093
Abstract: It is controversial to what extent endogenous gonadal hormone exposures influence executive functions in midlife women. Participants in the population-based Melbourne Women's Midlife Health Project were administered a battery of neuropsychological tests on two occasions 2 years apart. Tests of executive functions were the Trail Making Test (Part B), Tower of London (administered at baseline only), Symbol Digit Modalities Test, Digit Span Backward, and Letter-Number Sequencing. Estrone, free estradiol, and free testosterone levels were measured at the time of the first testing, and analyses were restricted to 147 women aged 56-64 years who had recently undergone natural menopause (mean age of menopause 53 years) and were not using hormone therapy. In multiple linear regression analyses, 2 of 20 baseline associations were significant at an alpha level of 0.05. Estrone concentrations were positively associated with Tower of London performance (p=0.02), and the ratio of free testosterone to free estradiol was positively associated with scores on the Symbol Digit Modalities Test score (p=0.04). No hormone measure was significantly predictive of 2-year change in executive functions performance. Significance levels in these exploratory analyses were unadjusted for multiple comparisons, and observed associations could be due to unique psychometric properties of these particular tasks or due to chance. Sex hormone binding globulin concentrations were unrelated to executive function scores. In recently postmenopausal women not receiving hormone therapy, serum concentrations of estrone, estradiol and testosterone, and the testosterone/estradiol ratio are not strongly associated with executive functions.
Publisher: Informa UK Limited
Date: 04-03-2020
Publisher: Informa UK Limited
Date: 27-06-2020
Publisher: Springer Science and Business Media LLC
Date: 14-05-2019
Publisher: Elsevier BV
Date: 11-2001
DOI: 10.1016/S1357-2725(01)00077-2
Abstract: Gastrin17gly acts as a growth factor for the colonic mucosa. Studies of the receptor involved have generally been restricted to its binding properties, and no investigation of the structure of gastrin17gly receptors on human colorectal carcinoma cell lines has yet been reported. The aim of this study was to optimise the conditions for binding of gastrin17gly to the human colorectal carcinoma cell line DLD-1, and to investigate the structure of the receptor responsible. Binding of 125I[Met15]gastrin17gly to DLD-1 cells was measured in competition experiments with increasing concentrations of either gastrin17gly or gastrin17, or with single concentrations of gastrin receptor antagonists. The molecular weights of the gastrin17gly binding proteins were determined by gel electrophoresis and autoradiography after covalent cross-linking of 125I[Nle15]gastrin2,17gly to cells or membranes with disuccinimidyl suberate. The IC50 value for binding of gastrin17gly to DLD-1 cells was 2.1+/-0.4 microM. Binding was inhibited by the non-selective gastrin/cholecystokinin receptor antagonists proglumide and benzotript, but not by the cholecystokinin-A receptor antagonist L364,718, or the gastrin/cholecystokinin-B receptor antagonist L365,260. The molecular weight of the major gastrin binding protein on DLD-1 cells or membranes was 70,000. We conclude that the major gastrin17gly binding site on the human colorectal carcinoma cell line DLD-1 is clearly distinct from the cholecystokinin-A and gastrin/cholecystokinin-B receptors, but is similar in some respects to the gastrin/cholecystokinin-C receptor.
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.IJCARD.2021.07.004
Abstract: Lower health-related quality of life (HRQoL) has been shown to predict a higher risk of hospital readmission and mortality in patients with cardiovascular disease (CVD). Few studies have explored the associations between HRQoL and incident CVD. We explored the associations between baseline HRQoL and incident and fatal CVD in community-dwelling older people in Australia and the United States. Longitudinal study using ASPirin in Reducing Events in the Elderly (ASPREE) trial data. This includes 19,106 in iduals aged 65-98 years, initially free of CVD, dementia, or disability, and followed between March 2010 and June 2017. The physical (PCS) and mental component scores (MCS) of HRQoL were assessed using the SF-12 questionnaire. Incident major adverse CVD events included fatal CVD (death due to atherothrombotic CVD), hospitalizations for heart failure, myocardial infarction or stroke. Analyses were performed using Cox proportional-hazard regression. Over a median 4.7 follow-up years, there were 922 incident CVD events, 203 fatal CVD events, 171 hospitalizations for heart failure, 355 fatal or nonfatal myocardial infarction and 403 fatal or nonfatal strokes. After adjustment for sociodemographic, health-related behaviours and clinical measures, a 10-unit higher PCS, but not MCS, was associated with a 14% lower risk of incident CVD, 28% lower risk of hospitalization for heart failure and 15% lower risk of myocardial infarction. Neither PCS nor MCS was associated with fatal CVD events or stroke. Physical HRQoL can be used in combination with clinical data to identify the incident CVD risk among older in iduals.
Publisher: Cold Spring Harbor Laboratory
Date: 14-10-2020
DOI: 10.1101/2020.10.11.20210963
Abstract: Few studies have measured the effect of genetic factors on dementia and cognitive decline in a population of healthy older in iduals followed prospectively. To examine the effect of Apolipoprotein E ( APOE ) genotypes and a polygenic risk score (PRS) on incident dementia and cognitive decline in a longitudinal cohort of healthy older people. Post-hoc genetic analysis of a randomized clinical trial population - the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrollment, participants had no history of diagnosed dementia, atherothrombotic cardiovascular disease, or permanent physical disability and were without cognitive impairment. Dementia (adjudicated trial endpoint) and cognitive decline, defined as a .5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence curves for all-cause dementia and cognitive decline were calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non- APOE variants. 12,978 participants with European ancestry were included 54.8% were female, and average age at baseline was 75 years (range 70 to 96). During a median 4.5 years of follow-up, 324 (2.5%) participants developed dementia and 503 (3.8%) died. Cumulative incidence of dementia to age 85 years was estimated to be 7.4% in all participants, 12.6% in APOE ε4 heterozygotes, 26.6% in ε4 homozygotes, 9.6% in the high PRS tertile, and 7.3% in the low PRS tertile. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3-fold increased risk of dementia and a 1.4/1.8-fold increased risk of cognitive decline, versus ε3/ε3 (P .001 for both). A high PRS (top tertile) was associated with a 1.4-fold increase risk of dementia, versus the low tertile (CI 1.04-1.76, P=0.02), but was not associated with cognitive decline risk (CI 0.96-1.22, P = 0.18). Incidence of dementia among healthy older in iduals is low across all genotypes however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not. How do genetic factors influence the risk of dementia and cognitive decline among healthy older in iduals? We studied cumulative incidence of dementia and cognitive decline in 12,978 healthy older in iduals without cardiovascular disease or cognitive impairment at enrollment, stratified by APOE genotype and a polygenic risk score (PRS). APOE ε4 and PRS increased the relative risk of dementia, but cumulative incidence was low across all genotypes. APOE genotypes were associated with cognitive decline, but PRS was not. Incidence of dementia is low among healthy older in iduals however, genetic factors still increase relative risk.
Publisher: Oxford University Press (OUP)
Date: 26-10-2018
DOI: 10.1093/IJE/DYX126
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-11-2009
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.JAD.2011.10.010
Abstract: Despite evidence of estrogen's mood-enhancing effects, the association between estrogen receptor (ER) gene variants and lifetime major depression has been insufficiently studied. 3987 community-dwelling women aged 65years and over were recruited in France as part of the Three City Study. Current and past major depressive disorders (MDD) were diagnosed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. The association between two common estrogen receptor alpha (ESR1) polymorphisms with lifetime MDD was examined using adjusted logistic regression models, taking into account the age at first depressive episode and the recurrence of depression. Women homozygous for the variant G allele of ESR1 rs9340799 had a 1.6-fold increased risk of MDD across their lifetime compared with women who were homozygous for the A allele (p=0.009). There was a similar non-significant trend for the C allele of rs2234693 being associated with an increased risk (p=0.09). Polytomous regression analysis further indicated that the GG genotype of rs9340799 was specifically associated with an increased risk of recurrent depressive episodes, regardless of the age at first onset of depression relative to the menopause. The duration and severity of depressive episodes was not considered in the analysis. This is the first study to examine the association between ESR1 gene variants and lifetime MDD. Our findings indicate a significant association between common variants and the risk of recurrent depressive episodes. This suggests that certain depressed women could be most responsive to hormone-based treatment.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
Publisher: Research Square Platform LLC
Date: 03-02-2020
Abstract: Background: Quality of life (QoL) is multi-dimensional concept of an in idual’ general well-being status in relation to their value, environment, cultural and social context in which they live. This study aimed to quantitatively synthesise available evidence on the association between QoL and mortality in the general population.Methods: An electronic search was conducted using three bibliographic databases, MEDLINE, EMBASE and PsycINFO. Inclusion criteria were studies that assessed QoL using standardized tools and examined mortality risk in a non-patient population. Qualitative data synthesis and meta-analyses using a random-effects model were performed.Results: Of 4,184 articles identified, 47 were eligible for inclusion, involving approximately 1,200,000 participants. Studies were highly heterogeneous in terms of QoL measures, population characteristics and data analysis. In total, 43 studies (91.5%) reported that better QoL was associated with lower mortality risk. The results of four meta-analyses indicated that higher health-related QoL (HRQoL) is associated with lower mortality risk, which was consistent for overall HRQoL (HR 0.633, 95% CI: 0.514 to 0.780), physical function (HR 0.987, 95% CI: 0.982 to 0.992), physical component score (OR 0.950, 95% CI: 0.935 to 0.965), and mental component score (OR 0.980, 95% CI: 0.969 to 0.992).Conclusion: These findings provide evidence that better QoL/HRQoL was associated with lower mortality risk. The utility of these measures in predicting mortality risk indicates that they should be considered further as potential screening tools in general clinical practice, beyond the traditional objective measures such as body mass index and the results of laboratory tests.
Publisher: Oxford University Press (OUP)
Date: 05-05-2020
Abstract: Patient-reported outcome measures (PROMs) captures the patient’s perspective regarding quality of life, daily functioning, symptom severity, and overall health, and how these may be impacted by health care or other interventions. PROMs are used in clinical quality registries (CQRs) for a number of diseases to assess the patient’s perspective of the impact of clinical care on quality-of-life. This scoping review aimed to identify dementia-specific PROMs, determine how the PROMs are being used, and whether they are used within dementia registries. Three electronic databases were searched using Medical Subject Heading terms for dementia, quality of life, and patient-reported outcomes. Data were extracted on the PROMs used and the methods and mode of administering the PROM. Seven dementia-specific PROMs were identified, however none were used in a dementia registry. All the PROMs were used at the patient level to identify patient needs and health service impacts. Three PROMs were also used at a system level to examine difference in care models. The majority of the PROMs were administered via a researcher or clinician and were predominantly completed by a proxy. PROMs provide an opportunity for a patient with dementia to share experiences and perspectives of care. A number of dementia-specific PROMs exist, yet none are used in dementia registries and the majority of studies utilize PROMs via a proxy. The use of PROM for patients with dementia, particularly in the context of dementia registries, requires further exploration and consideration.
Publisher: Research Square Platform LLC
Date: 29-09-2020
Abstract: Background: Quality of life (QoL) is multi-dimensional concept of an in idual’ general well-being status in relation to their value, environment, cultural and social context in which they live. This study aimed to quantitatively synthesise available evidence on the association between QoL and mortality in the general population. Methods: An electronic search was conducted using three bibliographic databases, MEDLINE, EMBASE and PsycINFO. Inclusion criteria were studies that assessed QoL using standardized tools and examined mortality risk in a non-patient population. Qualitative data synthesis and meta-analyses using a random-effects model were performed. Results: Of 4,184 articles identified, 47 were eligible for inclusion, involving approximately 1,200,000 participants. Studies were highly heterogeneous in terms of QoL measures, population characteristics and data analysis. In total, 43 studies (91.5%) reported that better QoL was associated with lower mortality risk. The results of four meta-analyses indicated that higher health-related QoL (HRQoL) is associated with lower mortality risk, which was consistent for overall HRQoL (HR 0.633, 95% CI: 0.514 to 0.780), physical function (HR 0.987, 95% CI: 0.982 to 0.992), physical component score (OR 0.950, 95% CI: 0.935 to 0.965), and mental component score (OR 0.980, 95% CI: 0.969 to 0.992). Conclusion: These findings provide evidence that better QoL/HRQoL was associated with lower mortality risk. The utility of these measures in predicting mortality risk indicates that they should be considered further as potential screening tools in general clinical practice, beyond the traditional objective measures such as body mass index and the results of laboratory tests.
Publisher: Research Square Platform LLC
Date: 14-08-2020
Abstract: Background: Quality of life (QoL) is multi-dimensional concept of an in idual’ general well-being status in relation to their value, environment, cultural and social context in which they live. This study aimed to quantitatively synthesise available evidence on the association between QoL and mortality in the general population.Methods: An electronic search was conducted using three bibliographic databases, MEDLINE, EMBASE and PsycINFO. Inclusion criteria were studies that assessed QoL using standardized tools and examined mortality risk in a non-patient population. Qualitative data synthesis and meta-analyses using a random-effects model were performed.Results: Of 4,184 articles identified, 47 were eligible for inclusion, involving approximately 1,200,000 participants. Studies were highly heterogeneous in terms of QoL measures, population characteristics and data analysis. In total, 43 studies (91.5%) reported that better QoL was associated with lower mortality risk. The results of four meta-analyses indicated that higher health-related QoL (HRQoL) is associated with lower mortality risk, which was consistent for overall HRQoL (HR 0.633, 95% CI: 0.514 to 0.780), physical function (HR 0.987, 95% CI: 0.982 to 0.992), physical component score (OR 0.950, 95% CI: 0.935 to 0.965), and mental component score (OR 0.980, 95% CI: 0.969 to 0.992).Conclusion: These findings provide evidence that better QoL/HRQoL was associated with lower mortality risk. The utility of these measures in predicting mortality risk indicates that they should be considered further as potential screening tools in general clinical practice, beyond the traditional objective measures such as body mass index and the results of laboratory tests.
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.NEUROBIOLAGING.2012.04.011
Abstract: Gonadal hormones may influence cognitive function. Postmenopausal midlife women in the population-based Melbourne Women's Midlife Health Project cohort were administered a comprehensive battery of neuropsychological tests on two occasions 2 years apart. Participants (n = 148, mean age 60 years) had undergone natural menopause and were not using hormone therapy. Estrone, total and free estradiol, and total and free testosterone levels were measured at time of the first testing. Principal-component analysis identified four cognitive factors. In multiple linear regression analyses, better semantic memory performance was associated with higher total (p = 0.02) and free (p = 0.03) estradiol levels and a lower ratio of testosterone to estradiol (p = 0.007). There were trends for associations between better verbal episodic memory and lower total testosterone (p = 0.08) and lower testosterone/estradiol ratio (p = 0.06). Lower free testosterone levels were associated with greater 2-year improvement on verbal episodic memory (p = 0.04) higher testosterone/estradiol predicted greater semantic memory improvement (p = 0.03). In postmenopausal midlife women, endogenous estradiol and testosterone levels and the testosterone/estradiol ratio are associated with semantic memory and verbal episodic memory abilities.
Publisher: Research Square Platform LLC
Date: 13-10-2020
Abstract: Background: Quality of life (QoL) is multi-dimensional concept of an in idual’ general well-being status in relation to their value, environment, cultural and social context in which they live. This study aimed to quantitatively synthesise available evidence on the association between QoL and mortality in the general population. Methods: An electronic search was conducted using three bibliographic databases, MEDLINE, EMBASE and PsycINFO. Inclusion criteria were studies that assessed QoL using standardized tools and examined mortality risk in a non-patient population. Qualitative data synthesis and meta-analyses using a random-effects model were performed. Results: Of 4,184 articles identified, 47 were eligible for inclusion, involving approximately 1,200,000 participants. Studies were highly heterogeneous in terms of QoL measures, population characteristics and data analysis. In total, 43 studies (91.5%) reported that better QoL was associated with lower mortality risk. The results of four meta-analyses indicated that higher health-related QoL (HRQoL) is associated with lower mortality risk, which was consistent for overall HRQoL (HR 0.633, 95% CI: 0.514 to 0.780), physical function (HR 0.987, 95% CI: 0.982 to 0.992), physical component score (OR 0.950, 95% CI: 0.935 to 0.965), and mental component score (OR 0.980, 95% CI: 0.969 to 0.992). Conclusion: These findings provide evidence that better QoL/HRQoL was associated with lower mortality risk. The utility of these measures in predicting mortality risk indicates that they should be considered further as potential screening tools in general clinical practice, beyond the traditional objective measures such as body mass index and the results of laboratory tests.
Publisher: Springer Science and Business Media LLC
Date: 18-08-2015
DOI: 10.1038/TP.2015.114
Abstract: The regulation of the brain-derived neurotrophic factor (BDNF) is important for depression pathophysiology and epigenetic regulation of the BDNF gene may be involved. This study investigated whether BDNF methylation is a marker of depression. One thousand and twenty-four participants were recruited as part of a longitudinal study of psychiatric disorders in general population elderly (age⩾65). Clinical levels of depression were assessed using the Mini International Neuropsychiatric Interview for the diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorder IV criteria, and the Centre for Epidemiologic Studies Depression Scale (CES-D) for assessment of moderate to severe depressive symptoms. Buccal DNA methylation at the two most widely studied BDNF promoters, I and IV, was investigated using the Sequenom MassARRAY platform that allows high-throughput investigation of methylation at in idual CpG sites within defined genomic regions. In multivariate linear regression analyses adjusted for a range of participant characteristics including antidepressant use, depression at baseline, as well as chronic late-life depression over the 12-year follow-up, were associated with overall higher BDNF methylation levels, with two sites showing significant associations (promoter I, Δ mean=0.4%, P =0.0002 promoter IV, Δ mean=5.4%, P =0.021). Three single-nucleotide polymorphisms ( rs6265 , rs7103411 and rs908867 ) were also found to modify the association between depression and promoter I methylation. As one of the largest epigenetic studies of depression, and the first investigating BDNF methylation in buccal tissue, our findings highlight the potential for buccal BDNF methylation to be a biomarker of depression.
Publisher: Springer Science and Business Media LLC
Date: 25-10-2017
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.EURONEURO.2013.06.003
Abstract: A plethora of data suggests a role for estrogen in cognitive function and genetic variants in the estrogen receptors ESR1 and ESR2 have been implicated in a range of hormone-sensitive diseases. It remains unknown however, whether ESR polymorphisms are associated with the risk of decline in specific domains of cognitive function. Data came from 3799 non-demented, community-dwelling elderly women recruited in France to the 3C Study. A short cognitive test battery was administered at baseline and 2, 4 and 7 years follow-up to assess global function, verbal fluency, visual memory, psychomotor speed and executive function. Detailed socio-demographic, behavioral, physical and mental health information was also gathered and genotyping of five common ESR1 and ESR2 polymorphisms was also performed. In multivariable-adjusted Cox analysis, ESR1 rs2234693 and rs9340799 were not significantly associated with the risk of decline on any of the cognitive tasks. However, significant associations with ESR2 polymorphisms were identified. The A allele of rs1256049 was associated with an increased risk of substantial decline in visual memory (HR:1.64, 95% CI: 1.23-2.18, p=0.0007), psychomotor speed (HR:1.43, 95% CI: 1.12-1.83, p=0.004), and on the incidence of Mild Cognitive Impairment (HR:1.31, 95% CI: 1.05-1.64, p=0.02). There was also a weaker association between the A allele of rs4986938 and a decreased risk of decline in psychomotor speed. Our large multicentre prospective study provides preliminary evidence that ESR2 genetic variants may be associated with specific cognitive domains and suggests that further examination of the role of this gene in cognitive function is warranted.
Publisher: Walter de Gruyter GmbH
Date: 20-12-2017
Abstract: The
Publisher: Wiley
Date: 17-09-2021
DOI: 10.1111/JGS.17435
Abstract: This study examined the risk of mortality in older adults with newly detected cognitive impairment or dementia. Data from the Australian cohort of the ASPirin in Reducing Events in the Elderly (ASPREE) trial were examined. The ASPREE clinical trial compared daily low‐dose aspirin to a placebo and involved 16,703 in iduals aged 70 years and over, who were without major cognitive impairment, physical disability, or cardiovascular disease at recruitment. During the trial, evidence of cognitive impairment, based on cognitive testing and medical record information, triggered dementia adjudication of participants using DSM‐IV criteria. Cox proportional hazard models were used to compare mortality rates across the dementia, trigger‐only, and no‐trigger groups. Over a median 4.7‐year follow‐up period, 806 participants triggered dementia adjudication, with 485 (60.2%) judged to have dementia. Following recruitment, mortality risks were 32.9, 33.6, and 10.8 events per 1000 person‐years in the dementia, trigger‐no‐dementia, and no‐trigger groups, respectively. In the fully adjusted model, mortality risks remained higher in the dementia and trigger‐no‐dementia groups, with hazard ratios of 1.7 (95% CI: 1.3–2.1) and 1.9 (95% CI: 1.5–2.6), respectively. There was no discernible difference between the dementia and trigger‐no‐dementia groups in mortality rates following recruitment, or following a dementia trigger. These two groups were more likely to die from sepsis, respiratory disease, and dementia, but less likely to die from cancer than the no‐trigger group, χ 2 = 161.5, p 0.001. ASPREE participants who triggered for a dementia evaluation experienced a substantially higher mortality rate than those who remained cognitively intact. The increase was indistinguishable among persons who met DSM‐IV criteria for dementia vs. those who triggered for a dementia evaluation but failed to meet DSM‐IV criteria. Future work should investigate whether earlier detection of cognitive decline can be used to identify and prevent early mortality.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2021
DOI: 10.1186/S12883-021-02331-4
Abstract: Brain age is a biomarker that predicts chronological age using neuroimaging features. Deviations of this predicted age from chronological age is considered a sign of age-related brain changes, or commonly referred to as brain ageing. The aim of this systematic review is to identify and synthesize the evidence for an association between lifestyle, health factors and diseases in adult populations, with brain ageing. This systematic review was undertaken in accordance with the PRISMA guidelines. A systematic search of Embase and Medline was conducted to identify relevant articles using search terms relating to the prediction of age from neuroimaging data or brain ageing. The tables of two recent review papers on brain ageing were also examined to identify additional articles. Studies were limited to adult humans (aged 18 years and above), from clinical or general populations. Exposures and study design of all types were also considered eligible. A systematic search identified 52 studies, which examined brain ageing in clinical and community dwelling adults (mean age between 21 to 78 years, ~ 37% were female). Most research came from studies of in iduals diagnosed with schizophrenia or Alzheimer’s disease, or healthy populations that were assessed cognitively. From these studies, psychiatric and neurologic diseases were most commonly associated with accelerated brain ageing, though not all studies drew the same conclusions. Evidence for all other exposures is nascent, and relatively inconsistent. Heterogenous methodologies, or methods of outcome ascertainment, were partly accountable. This systematic review summarised the current evidence for an association between genetic, lifestyle, health, or diseases and brain ageing. Overall there is good evidence to suggest schizophrenia and Alzheimer’s disease are associated with accelerated brain ageing. Evidence for all other exposures was mixed or limited. This was mostly due to a lack of independent replication, and inconsistency across studies that were primarily cross sectional in nature. Future research efforts should focus on replicating current findings, using prospective datasets. A copy of the review protocol can be accessed through PROSPERO, registration number CRD42020142817 .
Publisher: Wiley
Date: 08-02-2015
DOI: 10.1002/BRB3.313
Publisher: Springer Science and Business Media LLC
Date: 27-02-2020
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.BMCL.2007.10.113
Abstract: The synthesis and structure-activity relationships concerning 3,4,5-trisubstituted 1,2,4-triazoles as ghrelin receptor ligands are described. The importance of the starting aminoacid material as well as its configuration was explored and the (D) Trp residue was found to lead to the best agonist or antagonist compounds.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.PSYNEUEN.2019.104492
Abstract: Psychological stress is recognized as a major risk factor for a range of non-communicable diseases and possibly mortality. The extent to which the type and timing of stress exposure influences mortality, and potential differences between genders, remains unknown. To examine the association between early-life and recent stressful experiences and mortality risk in later life, and to determine possible gender differences in these associations. Data were obtained from 2152 French community-dwelling participants (aged ≥65). Questionnaires were used to evaluate recent stress, as well as retrospective reporting of childhood adversity. Mortality status was determined through death registries. Adjusted Cox proportional hazards models were used to determine the association between stress and 16-year mortality risk. Over a mean 12.9 years, 850 people died. Having a childhood home environment with very serious conflicts was associated with a 54% increased mortality risk (95%CI:1.21-1.96), and childhood abuse/maltreatment with a 34% increased risk (95% CI:1.05-1.70). For females, specific childhood events (serious illness HR:1.91, 95%CI:1.40-2.60 war/natural disaster HR:1.47, 95%CI:1.14-1.88) and the number of events (≥5 adverse events HR:1.91, 95%CI:1.25-2.32), also increased mortality risk. In terms of recent events, mortality risk increased by 66% (95%CI:1.39-2.00) in participants reporting a recent serious illness or physical trauma and by 86% for those reporting problems with the police/justice (95%CI:1.05-3.30). Among males specifically, mortality risk also increased with major financial problems (HR:1.92, 95%CI:1.14-3.21), and when they had a relative with a serious illness (HR:1.26, 95%CI:1.01-1.55). Stressful life experiences are associated with all-cause mortality however the associations varied between early-life adversities and recent stress, and were different across the genders. Among females, certain types of childhood adversity continue to predict mortality risk in later life, while in males specific recent stress significantly increased mortality risk.
Publisher: Wiley
Date: 21-07-2021
DOI: 10.1002/GPS.5601
Abstract: Social health reflects one’s ability to form interpersonal relationships. Poor social health is a risk factor for cardiovascular disease (CVD), however an in‐depth exploration of the link through CVD risk factors is lacking. To examine the relationship between social health (social isolation, social support, loneliness) and CVD risk factors among healthy older women and men. Data were from 11,498 healthy community‐dwelling Australians aged ≥70 years from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and the ASPREE Longitudinal Study of Older Persons sub‐study. Ten‐year CVD risk was estimated using the Atherosclerotic CVD Risk Scale (ASCVDRS) and the Framingham Risk Score (FRS). Physical inactivity and experiencing depressive symptoms were the only CVD risk factors that consistently differed by all three social health constructs. Loneliness was associated with greater ASCVDRS (women: β = 0.01, p 0.05 men: β = 0.03, p 0.001), social isolation with greater FRS (women: β = 0.02, p 0.01 men: β = 0.03, p 0.01) and the social health composite of being lonely (regardless of social isolation and/or social support status) with greater ASCVDRS (women: β = 0.01, p = 0.02 men: β = 0.03, p 0.001). Among men, loneliness was also associated with greater FRS ( β = 0.03, p 0.001) and social support with greater ASCVDRS ( β = 0.02, p = 0.01). Men were more socially isolated, less socially supported and less lonely than women. Social isolation, social support and loneliness displayed erse relationships with CVD risk factors and risk scores, emphasising the importance of distinguishing between these constructs. These findings inform on potential avenues to manage poor social health and CVD risk among older adults.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.PSYNEUEN.2018.01.004
Abstract: The aim of this study was to investigate placental DNA methylation of the oxytocin receptor gene (OXTR) in women with depression in pregnancy. We also explored the role of antidepressant medication in pregnancy on placental OXTR methylation. Data were obtained from 239 women in the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort. Current depressive disorders were diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID-IV). Depressive symptoms were measured during the third trimester in pregnancy using the Edinburgh Postnatal Depression Scale (EPDS). Plasma levels of antidepressant drugs were measured in maternal and cord blood obtained at delivery. OXTR DNA methylation was measured in placenta s les. Depressive symptoms in pregnancy were not associated with significant changes in DNA methylation of OXTR in the placenta. Cord plasma antidepressant levels were more strongly associated than maternal antidepressant dose or circulating blood antidepressant levels with increased DNA methylation of a specific unit within the promotor region of OXTR. This study provides preliminary data to suggest that antidepressant use during pregnancy can alter OXTR methylation in placental tissue. Our findings also indicate that the way exposures are measured in pregnancy can influence the direction and strength of findings. Future studies should investigate whether altered OXTR methylation might mediate the impacts of maternal antidepressant treatment on pregnancy and offspring outcomes.
Publisher: Springer Science and Business Media LLC
Date: 03-05-2021
Publisher: SERDI
Date: 2021
DOI: 10.14283/JFA.2021.20
Abstract: Frailty is associated with multiple adverse health outcomes, including mortality. Several methods have been used to characterize frailty, each based on different frailty scales. These include scales based on phenotype, multidomain, and deficit accumulations. Several systematic reviews have examined the association between frailty and mortality however, it is unclear whether these different frailty scales similarly predict mortality. This umbrella review aims to examine the association between frailty assessed by different frailty scales and all-cause mortality among community-dwelling older adults. A protocol was registered at PROSPERO, and it was conducted following the PRISMA statement. MEDLINE, Embase, PubMed, Cochrane Database of Systematic Reviews, Joanna Briggs Institute (JBI) EBP database, and Web of Science database was searched. Methodological quality was assessed using the JBI critical appraisal checklist and online AMSTAR-2 critical appraisal checklist. For eligible studies, essential information was extracted and synthesized qualitatively. Five systematic reviews were included, with a total of 434,115 participants. Three systematic reviews focused on single frailty scales one evaluated Fried’s physical frailty phenotype and its modifications another focused on the deficit accumulation frailty index. The third evaluated the FRAIL (Fatigue, Resistance, Ambulation, Illness, and Loss of weight) scale. The two other systematic reviews determined the association between frailty and mortality using different frailty scales. All of the systematic reviews found that frailty was significantly associated with all-cause mortality. This umbrella review demonstrates that frailty is a significant predictor of all-cause mortality, irrespective of the specific frailty scale.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-07-2021
Publisher: Cambridge University Press (CUP)
Date: 05-06-2008
Publisher: Wiley
Date: 2020
DOI: 10.1002/DAD2.12056
Publisher: Elsevier BV
Date: 08-2023
Publisher: Wiley
Date: 10-02-2022
DOI: 10.1002/SMI.3131
Abstract: Maternal stress during pregnancy is associated with differential DNA methylation in offspring and disrupted cortisol secretion. This study aimed to determine methylation signatures of cortisol levels in children, and whether associations differ based on maternal post‐traumatic stress disorder (PTSD). Blood epigenome‐wide methylation and fasting cortisol levels were measured in 118 offspring of mothers recruited from the Kosovo Rehabilitation Centre for Torture Victims. Mothers underwent clinically administered assessment for PTSD using Diagnostic and Statistical Manual of Mental Disorders. Correlations between offspring methylation and cortisol levels were examined using epigenome‐wide analysis, adjusting for covariates. Subsequent analysis focussed on a priori selected genes involved in the hypothalamic–pituitary–adrenal (HPA) axis stress signalling. Methylation at four sites were correlated with cortisol levels (cg15321696, r = −0.33, cg18105800, r = +0.33, cg00986889, r = −0.25, and cg15920527, r = −0.27). In adjusted multivariable regression, when stratifying based on prenatal PTSD status, significant associations were only found for children born to mothers with prenatal PTSD ( p 0.001). Several sites within HPA axis genes were also associated with cortisol levels in the maternal PTSD group specifically. There is evidence that methylation is associated with cortisol levels, particularly in offspring born to mothers with prenatal PTSD. However, larger studies need to be carried out to independently validate these findings.
Publisher: Future Medicine Ltd
Date: 07-2018
Abstract: Aim: Epigenetic changes, in particular in the placenta, may mediate the effects of prenatal alcohol exposure (PAE) on children's health. We examined the relationship between PAE patterns, based on dose and timing, and placental global DNA methylation. Methods: Using linear regression analysis, we examined the association between different PAE categories and placental global DNA methylation (n = 187), using the proxy measure of Alu-interspersed repeats. Results: Following adjustment for important covariates, we found no evidence of an association between PAE and placental global DNA methylation overall. However, when stratifying by newborn sex, PAE throughout pregnancy was associated with higher placental global DNA methylation (1.5% p = 0.01) of male newborns. Conclusion: PAE may have sex-specific effects on placental global DNA methylation if alcohol is consumed throughout pregnancy.
Publisher: Wiley
Date: 31-08-2007
Abstract: The 28-amino acid peptide ghrelin is a neuroendocrine hormone synthesized primarily in the stomach. It stimulates growth hormone secretion and appetite, thus promoting food intake and body-weight gain. The pharmacological properties of this peptide are mediated by the growth hormone secretagogue receptor type 1a (GHS-R1a). Given its wide spectrum of biological activities, it is evident that the discovery of ghrelin and its receptor has opened up many perspectives in the fields of neuroendocrine and metabolic research and has had an influence on such fields of internal medicine as gastroenterology, oncology, and cardiology. It is therefore increasingly likely that synthetic, peptidyl, and nonpeptidyl GHS-R1a ligands, acting as agonists, partial agonists, antagonists, or inverse agonists, could have both clinical and therapeutic potential. This review summarizes the various types of GHS-R1a ligands that have been described in the literature and discusses the recent progress made in this research area.
Publisher: Public Library of Science (PLoS)
Date: 23-03-2012
Publisher: Future Medicine Ltd
Date: 06-2021
Abstract: Aim: To investigate the association between maternal post-traumatic stress disorder (PTSD) during pregnancy and offspring DNA methylation and cortisol levels. Materials & methods: Blood genome-wide DNA methylation and cortisol was measured in the youngest child of 117 women who experienced sexual violence/torture during the Kosovo war. Results: Seventy-two percent of women had PTSD symptoms during pregnancy. Their children had higher cortisol levels and differential methylation at candidate genes ( NR3C1, HTR3A and BNDF) . No methylation differences reached epigenome-wide corrected significance levels. Conclusion: Identifying the biological processes whereby the negative effects of trauma are passed across generations and defining groups at high risk is a key step to breaking the intergenerational transmission of the effects of mental disorders.
Publisher: Wiley
Date: 06-2006
Publisher: Elsevier BV
Date: 05-2020
Publisher: Springer Science and Business Media LLC
Date: 21-10-2020
DOI: 10.1038/S41366-019-0472-3
Abstract: Leptin regulates satiety and energy homoeostasis, and plays a key role in placentation in pregnancy. Previous studies have demonstrated regulation of leptin gene (LEP) expression and/or methylation in placenta and cord blood in association with early life exposures, but most have been small and have not considered the influence of genetic variation. Here, we investigated the relationship between maternal factors in pregnancy, infant anthropometry and LEP genetic variation with LEP promoter methylation at birth and 12 months of age. LEP methylation was measured in cord (n = 877) and 12-month (n = 734) blood in the Barwon Infant Study, a population-based pre-birth cohort. Infant adiposity at birth and 12-months was measured as triceps and subscapular skinfold thickness. Cross-sectional regression tested associations of methylation with pregnancy and anthropometry measures, while longitudinal regression tested if birth anthropometry predicted 12-month LEP methylation levels. Male infants had lower LEP methylation in cord blood (-2.07% average methylation, 95% CI (-2.92, -1.22), p < 0.001). Genetic variation strongly influenced DNA methylation at a single CpG site, which was also negatively associated with birth weight (r = -0.10, p = 0.003). Pre-ecl sia was associated with lower cord blood methylation at another CpG site (-6.06%, 95% CI (-10.70, -1.42), p = 0.01). Gestational diabetes was more modestly associated with methylation at two other CpG units. Adiposity at birth was associated with 12-month LEP methylation, modified by rs41457646 genotype. There was no association of LEP methylation with 12-month anthropometric measures. Infant sex, weight, genetic variation, and exposure to pre-ecl sia and gestational diabetes, are associated with LEP methylation in cord blood. Infant adiposity at birth predicts 12-month blood LEP methylation in a genotype-dependent manner. These findings are consistent with genetics and anthropometry driving altered LEP epigenetic profile and expression in infancy. Further work is required to confirm this and to determine the long-term impact of altered LEP methylation on health.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Wiley
Date: 14-12-2021
DOI: 10.1002/PHAR.2652
Abstract: What is the association between anticholinergic burden and specific domains of cognitive function in older adults who are initially without major cognitive impairment? Post‐hoc analysis of longitudinal observational data from the ASPirin in Reducing Events in the Elderly (ASPREE) study. 19,114 participants from Australia and the United States aged 70 years and older (65 years and older for US minorities) were recruited and followed for a median of 4.7 years. At enrollment, participants were free of known cardiovascular disease, major physical disability, or dementia. Cognitive assessments administered at baseline and biennially at follow‐up visits included the Modified Mini‐Mental State examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT‐R) delayed recall, Controlled Oral Word Association Test (COWAT), and Symbol Digit Modalities Test (SDMT). Anticholinergic burden was calculated at baseline using the Anticholinergic Cognitive Burden (ACB) scale and grouped as scores of 0 (no burden), 1‐2 (low to moderate), or 3+ (high). Linear mixed effects models were used to assess the relationship between ACB score and cognition over time. After adjusting for sex, age, education, minority status, smoking status, hypertension, diabetes, depression, chronic kidney disease, country, and frailty, participants with a high ACB score had worse performance over time for 3MS (Adjusted [Adj] B=‐0.092, P=0.034), HVLT‐R delayed recall (Adj B=‐0.104, P .001), COWAT (Adj B=‐0.151, P .001), and SDMT (Adj B=‐0.129, P=0.026), than participants with an ACB score of 0. A low to moderate ACB score was also associated with worse performance over time for HVLT‐R delayed recall (Adj B=‐0.037, P=0.007) and COWAT (Adj B=‐0.065, P=0.003), compared to those with no ACB. Anticholinergic burden predicts worse cognitive function over time in initially dementia‐free older adults, particularly for executive function (COWAT) and episodic memory (HVLT‐R).
Publisher: MDPI AG
Date: 21-07-2022
DOI: 10.3390/NU14142983
Abstract: Later life changes in body weight may be associated with an increased risk of mortality in older adults. The objective of this study was to examine whether weight change over four years was associated with a 17-year mortality risk in older adults. Participants were 1664 community-dwelling adults aged ≥65 years in the longitudinal Enquete de Sante’ Psychologique-Risques, Incidence et Traitement (ESPRIT) study. Outcomes were all-cause mortality, cardiovascular disease (CVD) and cancer mortality. Weight change was defined as difference between weight at baseline and 4 years, categorised into: weight stable (± % weight change), weight loss (≥5%) and weight gain (≥5%). Association between weight change and mortality risk was evaluated using Cox proportional hazards models. Over 17 years of follow-up (median 15 years), 565 participants died. Compared to stable weight participants, those with ≥ 5% weight loss had an increased risk of all-cause mortality (HR: 1.24, 95% CI: 1.00–1.56, p = 0.05) and CVD mortality (HR: 1.53, 95% CI: 1.10–2.14, p = 0.01), but not cancer mortality (HR: 0.83, 95% CI: 0.50–1.39, p = 0.49). Weight gain of ≥5% was not associated with increased mortality (HR: 1.05, 95% CI: 0.76–1.45, p = 0.74). Weight monitoring in older adults could help identify weight loss at its early stages to better target interventions to maintain nutritional reserve and prevent premature mortality.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.PSYNEUEN.2016.11.016
Abstract: Variability in the serotonin transporter (5-HTTLPR) gene can influence the risk of depression associated with adversity, as well as cortisol stress reactivity, although not consistently. No study has examined the impact of both a stressful environment and corticotropic-axis dysfunction on depression, as a function of 5-HTTLPR. This population-based study included 334 subjects aged 65 and older. Depression was measured at both diagnostic (major depression according to DSM-IV) and symptomatic (subthreshold depression) levels of caseness, in addition to 5-HTTLPR and rs25531 genotyping and diurnal cortisol measures. For participants with the SS genotype, higher morning cortisol levels were associated with a 4-fold increased risk of depression. Among LL participants, both evening cortisol levels and recent stressful events increased depression risk, although only the latter remained significant after multivariable adjustment. Conversely, SL in iduals appeared somewhat resilient to depression in terms of cortisol and recent stress. These findings indicate that 5-HTTLPR genetic variability appears to influence the association between stress-related factors and late-life depression, although the gene-environment interactions failed to reach statistical significance levels. Participants homozygous for the short allele appeared to have a cortisol-related neuroendocrine vulnerability to depression, while long allele homozygotes were more reactive to stressful events in terms of depression risk.
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.NEUROBIOLAGING.2010.07.014
Abstract: Gonadal hormones may influence cognitive function. Postmenopausal midlife women in the population-based Melbourne Women's Midlife Health Project cohort were administered a comprehensive battery of neuropsychological tests on two occasions 2 years apart. Participants (n = 148, mean age 60 years) had undergone natural menopause and were not using hormone therapy. Estrone, total and free estradiol, and total and free testosterone levels were measured at time of the first testing. Principal-component analysis identified four cognitive factors. In multiple linear regression analyses, better semantic memory performance was associated with higher total (p = 0.02) and free (p = 0.03) estradiol levels and a lower ratio of testosterone to estradiol (p = 0.007). There were trends for associations between better verbal episodic memory and lower total testosterone (p = 0.08) and lower testosterone/estradiol ratio (p = 0.06). Lower free testosterone levels were associated with greater 2-year improvement on verbal episodic memory (p = 0.04) higher testosterone/estradiol predicted greater semantic memory improvement (p = 0.03). In postmenopausal midlife women, endogenous estradiol and testosterone levels and the testosterone/estradiol ratio are associated with semantic memory and verbal episodic memory abilities.
Publisher: Springer Science and Business Media LLC
Date: 15-02-2017
DOI: 10.1038/SREP42676
Abstract: Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors ( ADRs ) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. Eight single-nucleotide polymorphisms (SNPs) involved with adrenergic function were genotyped adrenergic receptors alpha(1A) ( ADRA1A ), alpha(2A) ( ADRA2A ), and beta2 ( ADRB2 ) and transcription factor TCF7L2 . Questionnaires evaluated recent stressful life events as well as early environment during childhood and adolescence. Using multivariate logistic regression analyses four SNPs were significantly associated with GAD. A 4-fold modified risk was found with ADRA1A rs17426222 and rs573514, and ADRB2 rs1042713 which remained significant after Bonferroni correction. Certain variants may moderate the effect of adverse life events on the risk of GAD. Replication in larger s les is needed due to the small case number. This is the first study showing that ADR variants are susceptibility factors for GAD, further highlighting the critical role of the adrenergic nervous system in this disorder.
Publisher: Springer Science and Business Media LLC
Date: 19-04-2022
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.JAD.2008.09.007
Abstract: The impact of hormone therapy use on late-life anxiety disorder in elderly women has not been evaluated. Anxiety disorders were evaluated in 838 community-dwelling postmenopausal women aged 65 years and over, randomly recruited from electoral rolls. Anxiety disorders were assessed using a standardized psychiatric examination based on DSM-IV criteria, at baseline and as part of the 2- and 4-year follow-up. Multivariate logistic regression analyses adjusted for socio-demographic variables, measures of physical health and cognitive impairment, as well as current depressive symptomatology indicated no significant association between hormone therapy and anxiety disorders at baseline or after the 4-year follow-up period, regardless of type of treatment. Compared to women who have never taken hormonal therapy, no significant difference was observed for women taking continuously hormone therapy over the follow-up or those who stopped their treatment. The use of hormone therapy was not associated with improved anxiety symptomatology in elderly postmenopausal women.
Publisher: BMJ
Date: 09-2022
DOI: 10.1136/BMJOPEN-2022-061854
Abstract: The Australian Temperament Project Generation 3 Study (ATPG3) was established to examine the extent to which offspring social and emotional development is shaped in the decades prior to conception, in parent and grandparent histories of psychosocial adjustment (eg, emotional regulation, relationship quality and prosociality) and maladjustment (eg, depressive symptoms, substance use and antisociality). The Australian Temperament Project (ATP) commenced in 1983 as a population representative survey of the social and emotional health of 2443 young Australians (Generation 2: 4–8 months old) and their parents (Generation 1). Since then, families have been followed from infancy to young adulthood (16 waves). Between 2012 and 2018, the cohort was screened biannually for pregnancies (Generation 3), with assessments conducted in the third trimester of pregnancy, and at 8 weeks and 1 year postpartum. A total of 1167 offspring (607 female) born to 703 Generation 2 parents (400 mothers) were recruited into the ATPG3 Study. Findings to date highlight: (1) strong continuities in depressive symptoms and substance use from adolescence through to becoming a parent (2) a role for persistent preconception mental health problems in risk for parent–child bonding difficulties, as well as infant emotional reactivity and behaviour problems (3) the importance of secure attachments in adolescence in reducing long-term risk for postpartum mental health problems and (4) the protective nature of perceived social support, both preconception and postpartum, in strengthening relationship quality and social support during the COVID-19 pandemic. Assessments of ATPG3 families in preschool and middle childhood are currently funded and underway. We intend to maintain the offspring cohort through childhood, adolescence, young adulthood and into parenthood. Data will be used to map preconception determinants of emotional health, and enhance approaches to population monitoring and targeted intervention over the life course and across generations.
Publisher: Informa UK Limited
Date: 05-07-2021
Publisher: Springer Science and Business Media LLC
Date: 14-07-2012
DOI: 10.1007/S00726-012-1355-2
Abstract: Ghrelin is a 28-residue peptide acylated with an n-octanoyl group on the Ser 3 residue, predominantly produced by the stomach. Ghrelin displays strong growth hormone (GH) releasing activity, which is mediated by the activation of the so-called GH secretagogue receptor type 1a (GHS-R1a). Given the wide spectrum of biological activities of Ghrelin in neuroendocrine and metabolic pathways, many research groups, including our group, developed synthetic peptide, and nonpeptide GHS-R1a ligands, acting as agonists, partial agonists, antagonists, or inverse agonists. In this highlight article, we will focus on the discovery of a GHS-R1a antagonist compound, JMV 2959, which has been extensively studied in different in vitro and in vivo models. We will first describe the peptidomimetic approach that led us to discover this compound. Then we will review the results obtained with this compound in different studies in the fields of food intake and obesity, addictive behaviors, hyperactivity and retinopathy.
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1053/J.GASTRO.2007.08.023
Abstract: Aberrant activation of the beta-catenin/Tcf-4 transcriptional complex represents an initiating event for colorectal carcinogenesis, shifting the balance from differentiation toward proliferation in colonic crypts. Here, we assessed whether endogenous progastrin, encoded by a target gene of this complex, was in turn able to regulate beta-catenin/Tcf-4 activity in adenomatous polyposis coli (APC)-mutated cells, and we analyzed the impact of topical progastrin depletion on intestinal tumor growth in vivo. Stable or transient RNA silencing of the GAST gene was induced in human tumor cells and in mice carrying a heterozygous Apc mutation (APCDelta14), which overexpress progastrin but not amidated or glycine-extended gastrin. Depletion of endogenous progastrin production strongly decreased intestinal tumor growth in vivo through a marked inhibition of constitutive beta-catenin/Tcf-4 activity in tumor cells. This effect was mediated by the de novo expression of the inhibitor of beta-catenin and Tcf-4 (ICAT), resulting from a down-regulation of integrin-linked kinase in progastrin-depleted cells. Accordingly, ICAT down-regulation was correlated with progastrin overexpression and Tcf-4 target gene activation in human colorectal tumors, and ICAT repression was detected in the colon epithelium of tumor-prone, progastrin-overexpressing mice. In APCDelta14 mice, small interfering RNA-mediated progastrin depletion not only reduced intestinal tumor size and numbers, but also increased goblet cell lineage differentiation and cell apoptosis in the remaining adenomas. Thus, depletion of endogenous progastrin inhibits the tumorigenicity of APC-mutated colorectal cancer cells in vivo by promoting ICAT expression, thereby counteracting Tcf-4 activity. Progastrin targeting strategies should provide an exciting prospect for the differentiation therapy of colorectal cancer.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.PSCYCHRESNS.2018.12.012
Abstract: Prior research indicates that socioeconomic disadvantage is associated with prefrontal cortical (PFC) development in childhood and adolescence, however the mechanisms of this link are unclear. This study investigated whether DNA methylation of the brain-derived neurotrophic factor (BDNF, which plays a key role in synaptic plasticity), mediated the association between neighborhood disadvantage and thickness of the PFC in adolescents. Neighborhood disadvantage was measured in 33 adolescents aged 12-13 years using the Socio-Economic Indexes for Areas. Buccal swabs, collected during mid-adolescence (aged 16-18 years), enabled BDNF DNA methylation of the widely studied exon IV promoter region to be measured. Cortical thickness was assessed during late-adolescence (aged 18-20 years) via T1-weighted magnetic resonance imaging (MRI). A significant negative association between disadvantage and BDNF DNA methylation at a specific site of the exon IV promoter was identified. Lower levels of methylation were also significantly associated with greater thickness of the lateral orbitofrontal cortex (lOFC), and right medial OFC. Lower levels of DNA methylation at this site also mediated associations between higher disadvantage and thinner bilateral lOFC thickness. These novel findings give insight into a potential biological mechanism that could further our understanding as to why brain development is affected by varying environmental exposures.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Informa UK Limited
Date: 23-05-2019
DOI: 10.1080/13607863.2018.1474445
Abstract: To ascertain the trajectories of mental health among women in Australia assessed in repeat waves from their early 70 s to the end of their lives or their mid 80 s. Secondary analysis of data contributed by the 1921-26 cohort of the Australian Longitudinal Study of Women's Health Waves 1-6. Primary outcome was the 4-item SF-36 Vitality Subscale, which assesses mental health as life satisfaction, social participation, energy and enthusiasm. Structural, in idual and intermediary factors were assessed using study-specific and standardised measures. Trajectories were identified using Growth Mixture Modelling and associations with baseline characteristics with Structural Equation Modelling. 12,432 women completed Survey One. Three mental health trajectories: stable high (77%) stable low (18.2%) and declining from high to low (4.8%) were identified. Compared to the stable high group, women in the stable low group were significantly less physically active, had more nutritional risks, more recent adverse life events, fewer social interactions and less social support, reported more stress and were more likely to have a serious illness or disability at Survey One. The declining group had similar characteristics to the stable high group, but were significantly more likely to report at baseline that they had experienced recent financial, physical and emotional elder abuse. These interact, but not directly with socioeconomic position and marital status. Mental health among older women is related to social relationships, general health, access to physical activity and healthy nutrition, coincidental adverse life events and experiences of interpersonal violence, in particular elder abuse.
Publisher: Wiley
Date: 2023
DOI: 10.1002/DAD2.12388
Abstract: This study investigated whether grip strength and gait speed predict cognitive aging trajectories and examined potential sex‐specific associations. Community‐dwelling older adults ( n = 19,114) were followed for up to 7 years, with regular assessment of global function, episodic memory, psychomotor speed, and executive function. Group‐based multi‐trajectory modeling identified joint cognitive trajectories. Multinomial logistic regression examined the association of grip strength and gait speed at baseline with cognitive trajectories. High performers (14.3%, n = 2298) and low performers (4.0%, n = 642) were compared to the average performers (21.8%, n = 3492). Grip strength and gait speed were positively associated with high performance and negatively with low performance ( P ‐values 0.01). The association between grip strength and high performance was stronger in women (interaction P 0.001), while gait speed was a stronger predictor of low performance in men (interaction P 0.05). Grip strength and gait speed are associated with cognitive trajectories in older age, but with sex differences. There is inter‐in idual variability in late‐life cognitive trajectories. Grip strength and gait speed predicted cognitive trajectories in older age. However, sex‐specific associations were identified. In women, grip strength strongly predicted high, compared to average, trajectory. In men, gait speed was a stronger predictor of low cognitive performance trajectory.
Publisher: BMJ
Date: 24-03-2017
Publisher: Springer Science and Business Media LLC
Date: 03-01-2021
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.CARDFAIL.2021.12.014
Abstract: We sought to determine the association between heart failure (HF) and cognitive change and dementia. Systematic search of three electronic databases was performed and 29 eligible studies involving approximately 3 million participants were identified. Twelve studies examined dementia and 20 cognitive change, but only a subset of studies could be included in the meta-analysis. These findings indicated that HF was not significantly associated with dementia (n = 8, hazard ratio 1.18, 95% confidence interval 0.93-1.50), but increased the risk of cognitive impairment (n = 3, hazard ratio 1.80, 95% confidence interval 1.14-2.86) . Additionally, HF was associated with poorer mean cognitive performance in global cognition (Hedges' g -0.73, 95% confidence interval -1.12 to -0.35), memory (Hedges' g -0.57, 95% confidence interval -0.72 to -0.42), executive function (Hedges' g -0.58, 95% confidence interval -0.72 to -0.43), attention/speed (Hedges' g -0.50, 95% confidence interval -0.63 to -0.37) and language (Hedges' g -0.61, 95% confidence interval -1.05 to -0.17). Patients with HF perform worse on all cognitive tests and have an increased risk of cognitive impairment. These findings highlight the need for clinicians to consider cognition as part of routine care for patients with HF.
Publisher: Oxford University Press (OUP)
Date: 04-04-2022
Abstract: We provide new evidence on the profiles of social isolation, social support, and loneliness before and after spousal death for older widows. We also examine the moderating effects of gender and financial resources on changes in social health before and after widowhood. We use 19 waves of data from the Household, Income and Labour Dynamics in Australia Survey, including 749 widowed in iduals and a comparison group of around 8,000 married in iduals. We apply coarsened exact matching weights and control for age and time trends. Local polynomial smoothed plots show the profiles of social health from 3 years pre- to 3 years postspousal death. All analyses were stratified by gender. Spousal death was strongly associated with increased loneliness for women and men, but also an increase in interactions with friends and family not living with the bereaved. For men, financial resources (both income and asset wealth) provided some protection against loneliness. Spousal death was not associated with changes in social support or participation in community activities. We demonstrate that loneliness is a greater challenge of widowhood than social isolation or a lack of social support. Our findings suggest that interventions focusing only on increasing social interactions are unlikely to alleviate loneliness following spousal death. Moreover, policies that reduce the cost of formal social participation may have limited effectiveness in tackling loneliness, particularly for women. Alternative strategies, such as helping the bereaved form a new sense of identity and screening for loneliness around widowhood by health care workers, could be beneficial.
Publisher: Wiley
Date: 31-10-2007
Publisher: Physicians Postgraduate Press, Inc
Date: 10-08-2010
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: Wiley
Date: 07-05-2014
Abstract: To determine whether premature menopause (≤40 years) can have long-lasting effects on later-life cognition and investigate whether this association varies depending on the type of menopause and use of hormone treatment (HT). Population-based cohort study. The French Three-City Study. Four thousand eight hundred and sixty-eight women aged at least 65 years. Multivariable-adjusted logistic regression models were used to determine the association between age at menopause, type of menopause (surgical, natural), and the use of menopausal HT and later-life cognitive function. Performance on a cognitive test battery (at baseline and over 7 years) and clinical dementia diagnosis. Menopause at or before the age of 40 years, both premature bilateral ovariectomy and premature ovarian failure (non-surgical loss of ovarian function), was associated with worse verbal fluency (OR 1.56, 95%CI 1.12-1.87, P=0.004) and visual memory (OR 1.39, 95%CI 1.09-1.77, P=0.007) in later life. HT at the time of premature menopause appeared beneficial for later-life visual memory but increased the risk of poor verbal fluency. Type of menopause was not significantly associated with cognitive function. Premature menopause was associated with a 30% increased risk of decline in psychomotor speed and global cognitive function over 7 years. Both premature surgical menopause and premature ovarian failure were associated with long-term negative effects on cognitive function, which are not entirely offset by menopausal HT. In terms of surgical menopause, these results suggest that the potential long-term effects on cognitive function should form part of the risk/benefit ratio when considering ovariectomy in younger women.
Publisher: Frontiers Media SA
Date: 09-08-2017
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: Cambridge University Press (CUP)
Date: 15-01-2016
DOI: 10.1017/S2045796015001122
Abstract: In elderly general population sub-syndromal clinically significant levels of depressive symptoms are highly prevalent and associated with high co-morbidity and increased mortality risk. However changes in depressive symptoms over time and etiologic factors have been difficult to characterise notably due to methodological shortcomings. Our objective was to differentiate trajectories of depressive symptoms over 10 years in community-dwelling elderly men and women using statistical modelling methods which take into account intra-subject correlation and in idual differences as well as to examine current and life-time risk factors associated with different trajectories. Participants aged 65 and over were administered standardised questionnaires and underwent clinical examinations at baseline and after 2, 4, 7 and 10 years. Trajectories over time of the Center for Epidemiologic Studies Depression scores were modelled in 517 men and 736 women separately with latent class mixed models which include both a linear mixed model to describe latent classes of trajectories and a multinomial logistic model to characterise the latent trajectories according to baseline covariates (socio-demographic, lifestyle, clinical, genetic characteristics and stressful life events). In both genders two different profiles of symptom changes were observed over the 10-year follow-up. For 9.1% of men and 25% of women a high depressive symptom trajectory was found with a trend toward worsening in men. The majority of the remaining men and women showed decreasing symptomatology over time, falling from clinically significant to very low levels of depressive symptoms. In large multivariate class membership models, mobility limitations [odds ratio (OR) = 4.5, 95% confidence interval (CI) 1.6–12.9 and OR = 4.9, 95% CI 2.3–10.7, in men and women respectively], ischemic pathologies (OR = 2.9, 95% CI 1.0–8.3 and OR = 3.1, 95% CI 1.0–9.9), and recent stressful events (OR = 4.5, 95% CI 1.1–18.5, OR = 3.2, 95% CI 1.6–6.2) were associated with a poor symptom course in both gender as well as diabetes in men (OR = 3.5, 95% CI 1.1–10.9) and childhood traumatic experiences in women (OR = 3.1, 95% CI 1.6–5.8). This prospective study was able to differentiate patterns of chronic and remitting depressive symptoms in elderly people with distinct symptom courses and risk factors for men and women. These findings may inform prevention programmes designed to reduce the chronic course of depressive symptomatology.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.JAD.2015.12.048
Abstract: Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with heritability of up to 38%. The fat mass- and obesity-associated (FTO) gene, in particular the single nucleotide polymorphism (SNP) rs9939609, has been identified as a genetic risk loci associated with MDD. However, most prior studies have involved European and American populations. Whether rs9939609 is an true risk SNP for MDD in Asian populations remains inconclusive. In the present study, we conducted a meta-analysis of the association between rs9939609 and MDD in Asian populations by combining 5 available case-control s les totaling 6531 cases and 12,359 controls. Our meta-analysis suggests that rs9939609 is not a risk SNP for MDD in Asian populations by fixed effect model (Z=1.04, P=0.30, OR=0.96, 95% CI=0.90-1.03). The age distribution and gender ratios were not matched well in the combined s les of cases and controls. Publication bias might be also considered with only a relatively small number of association studies of FTO rs9939609 with MDD in Asian populations. The absence of association of rs9939609 with MDD in our Asian populations suggests a potential genetic heterogeneity in the susceptibility of MDD on this locus.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-07-2021
Abstract: Blood pressure variability (BPV) in midlife increases risk of late‐life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long‐term, visit‐to‐visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow‐up visits. Time‐to‐event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. In iduals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction P =0.02), with increased risk in men (HR, 1.68 95% CI, 1.19–2.39) but not women (HR, 1.01 95% CI, 0.72–1.42). For cognitive decline, similar increased risks were observed for men and women (interaction P =0.15 men: HR, 1.36 95% CI, 1.16–1.59 women: HR, 1.14 95% CI, 0.98–1.32). High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. URL: www.clinicaltrials.gov Unique identifier: NCT01038583 isrctn.com . Identifier: ISRCTN83772183.
Publisher: Springer Science and Business Media LLC
Date: 10-2014
Publisher: American Association for Cancer Research (AACR)
Date: 29-07-2009
DOI: 10.1158/0008-5472.CAN-08-2409
Abstract: The Wnt and Notch signaling pathways are both abnormally activated in colorectal cancer (CRC). We recently showed that progastrin depletion inhibited Wnt signaling and increased goblet cell differentiation of CRC cells. Here, we show that progastrin down-regulation restores the expression by CRC cells of the early secretory lineage marker Math-1/Hath-1 due to an inhibition of Notch signaling. This effect is mediated by a decreased transcription of the Notch ligand Jagged-1, downstream of β-catenin/Tcf-4. Accordingly, recombinant progastrin sequentially activated the transcription of Wnt and Notch target genes in progastrin-depleted cells. In addition, restoration of Jagged-1 levels in these cells is sufficient to activate Tcf-4 activity, demonstrating the occurrence of a feedback regulation from Notch toward Wnt signaling. These results suggest that progastrin could be instrumental in maintaining the concomitant activation of Wnt and Notch pathways in CRC cells, further highlighting the interest of progastrin targeting for the clinical management of CRC. [Cancer Res 2009 (15):6065–73]
Publisher: BMJ
Date: 22-02-2023
Abstract: Social prescribing (SP) enables healthcare professionals to link patients with non-medical interventions available in the community to address underlying socioeconomic and behavioural determinants. We synthesised the evidence to understand the effectiveness of SP for chronic disease prevention. A systematic literature search was conducted using five databases and two registries. Eligible studies included randomised controlled trials of SP among community-dwelling adults recruited from primary care or community setting, investigating any chronic disease risk factors defined by the WHO (behavioural factors: smoking, physical inactivity, unhealthy diet and excessive alcohol consumption metabolic factors: raised blood pressure, overweight/obesity, hyperlipidaemia and hyperglycaemia). Random effect meta-analyses were performed at two time points: completion of intervention and follow-up after trial. We identified nine reports from eight trials totalling 4621 participants. All studies evaluated SP exercise interventions which were highly heterogeneous regarding the content, duration, frequency and length of follow-up. Majority of studies had some concerns for risk of bias. Meta-analysis revealed that SP likely increased physical activity (completion: mean difference (MD) 21 min/week, 95% CI 3 to 39, I 2 =0% follow-up ≤12 months: MD 19 min/week, 95% CI 8 to 29, I 2 =0%). However, SP may not improve markers of adiposity, blood pressure, glucose and serum lipid. There were no eligible studies that primarily target unhealthy diet, smoking and excessive alcohol drinking behaviours. SP exercise interventions probably increased physical activity slightly however, no benefits were observed for metabolic factors. Determining whether SP is effective in modifying the determinants of chronic diseases and promotes sustainable healthy behaviours is limited by the current evidence of quantification and uncertainty, warranting further rigorous studies. CRD42022346687.
Publisher: Royal College of Psychiatrists
Date: 10-2013
DOI: 10.1192/BJP.BP.112.124685
Abstract: There are conflicting data on the role of anxiety in predicting mortality. To evaluate the 10-year mortality risk associated with anxiety in community-dwelling elderly people. Using data from 718 men and 1046 women aged 65 years and over, gender-stratified associations of anxiety symptoms (Spielberger State–Trait Anxiety Inventory, third tertile) and current DSM-IV anxiety disorder including generalised anxiety disorder (GAD) and phobia with all-cause and cardiovascular mortality were determined. In women, mortality risk was increased for anxiety disorder and GAD in multivariate Cox models (hazard ratio (HR) = 1.53, 95% Cl 1.02-2.27 and HR = 2.04, 95% Cl 1.08-3.86 respectively), whereas for phobia it was nearly significant (HR= 1.52, 95% Cl 0.94-2.47). Anxiety trait symptoms became non-significant as a result of the confounding effect of depressive symptoms. Anxiety disorder was associated with cardiovascular mortality in univariate analysis (HR = 2.42, 95% Cl 1.16-5.07). No significant associations were found in men. Our study suggests a gender-specific association of anxiety and mortality.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-03-2020
DOI: 10.1212/WNL.0000000000009277
Abstract: To determine the effect of low-dose aspirin vs placebo on incident all-cause dementia, incident Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitive decline in older in iduals. Aspirin in Reducing Events in the Elderly (ASPREE) was a double-blind, placebo-controlled trial of low-dose aspirin. In the United States and Australia, community-dwelling in iduals aged ≥70 years (US minorities ≥65 years) and free of cardiovascular disease, physical disability, and diagnosed dementia were enrolled. Participants were randomized 1:1–100 mg daily aspirin or placebo. The Modified Mini-Mental State Examination, Hopkins Verbal Learning Test–Revised, Symbol Digit Modalities Test, and Controlled Oral Word Association Test assessed cognition at baseline and over follow-up. Additional cognitive testing was performed in participants with suspected dementia (“trigger”) based on within-study assessments or clinical history. Dementia was adjudicated according to DSM-IV criteria. National Institute on Aging–Alzheimer’s Association criteria were used for AD and MCI subclassification. A total of 19,114 participants were followed over a median 4.7 years and 964 triggered further dementia assessments. There were 575 adjudicated dementia cases, and 41% were classified as clinically probable AD. There was no substantial difference in the risk of all dementia triggers (hazard ratio [HR], 1.03 95% confidence interval [CI], 0.91–1.17), probable AD (HR, 0.96 95% CI, 0.74–1.24), or MCI (HR, 1.12 95% CI, 0.92–1.37) between aspirin and placebo. Cognitive change over time was similar in the aspirin and placebo groups. There was no evidence that aspirin was effective in reducing risk of dementia, MCI, or cognitive decline. Follow-up of these outcomes after initial exposure is ongoing. This study provides Class II evidence that for healthy older in iduals, low-dose aspirin does not significantly reduce the incidence of dementia, probable AD, MCI, or cognitive decline. NCT01038583.
Publisher: S. Karger AG
Date: 2023
DOI: 10.1159/000528984
Abstract: b i Introduction: /i /b Frailty is a common geriatric syndrome that adversely impacts health outcomes. This study examined correlates of physical frailty in healthy community-dwelling older adults and studied the effect of frailty on disability-free survival (DFS), defined as survival free of independence-limiting physical disability or dementia. b i Methods: /i /b This is a post hoc analysis of 19,114 community-dwelling older adults (median age: 74.0 years, interquartile range or IQR: 6.1 years) from Australia and the USA enrolled in the “ASPirin in Reducing Events in the Elderly (ASPREE)” clinical trial. Frailty was assessed using a modified Fried phenotype and a deficit accumulation frailty index (FI) utilizing a ratio score derived from 66 items. Multinomial logistic regression was used to examine the correlates of frailty and Cox regression to analyze the association between frailty and DFS (and its components). b i Results: /i /b At study enrollment, 39.0% were prefrail, and 2.2% of participants were frail, according to Fried phenotype. Older age, higher waist circumference, lower education, ethnoracial origin, current smoking, depression, and polypharmacy were associated with prefrailty and frailty according to Fried phenotype and FI. Fried phenotype defined prefrailty and frailty predicted reduced DFS (prefrail: HR: 1.67 95% CI: 1.50–1.86 and frail: HR: 2.80 95% CI: 2.27–3.46), affecting each component of DFS including dementia, physical disability, and mortality. Effect sizes were larger, according to FI. b i Conclusion: /i /b Our study showed that prefrailty is common in community-dwelling older adults initially free of cardiovascular disease, dementia, or independence-limiting physical disability. Prefrailty and frailty significantly reduced disability-free survival. Addressing modifiable correlates, like depression and polypharmacy, might reduce the adverse impact of frailty on dementia-free and physical disability-free survival.
Publisher: Wiley
Date: 27-02-2023
DOI: 10.1111/CEN.14898
Abstract: The role of circulating sex hormones on structural brain ageing is yet to be established. This study explored whether concentrations of circulating sex hormones in older women are associated with the baseline and longitudinal changes in structural brain ageing, defined by the brain‐predicted age difference (brain‐PAD). Prospective cohort study using data from NEURO and Sex Hormones in Older Women substudies of the ASPirin in Reducing Events in the Elderly clinical trial. Community‐dwelling older women (aged 70+ years). Oestrone, testosterone, dehydroepiandrosterone (DHEA), and sex‐hormone binding globulin (SHBG) were quantified from plasma s les collected at baseline. T1‐weighted magnetic resonance imaging was performed at baseline, 1 and 3 years. Brain age was derived from whole brain volume using a validated algorithm. The s le comprised of 207 women not taking medications known to influence sex hormone concentrations. A statistically higher baseline brain‐PAD (older brain age relative to chronological age) was seen for women in the highest DHEA tertile compared with the lowest in the unadjusted analysis ( p = .04). This was not significant when adjusted for chronological age, and potential confounding health and behavioural factors. Oestrone, testosterone and SHBG were not associated with brain‐PAD cross‐sectionally, nor were any of the examined sex hormones or SHBG associated with brain‐PAD longitudinally. No strong evidence of an association between circulating sex hormones and brain‐PAD. Given there is prior evidence to suggests sex hormones may be important for brain ageing, further studies of circulating sex hormones and brain health in postmenopausal women are warranted.
Publisher: Frontiers Media SA
Date: 19-06-2018
Publisher: Wiley
Date: 08-11-2017
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.CLINBIOCHEM.2018.05.020
Abstract: As the prevalence of Alzheimer's disease (AD) increases, the search for a definitive, easy to access diagnostic biomarker has become increasingly important. Micro RNA (miRNA), involved in the epigenetic regulation of protein synthesis, is a biological mark which varies in association with a number of disease states, possibly including AD. Here we comprehensively review methods and findings from 26 studies comparing the measurement of miRNA in blood between AD cases and controls. Thirteen of these studies used receiver operator characteristic (ROC) analysis to determine the diagnostic accuracy of identified miRNA to predict AD, and three studies did this with a machine learning approach. Of 8098 in idually measured miRNAs, 23 that were differentially expressed between AD cases and controls were found to be significant in two or more studies. Only six of these were consistent in their direction of expression between studies (miR-107, miR-125b, miR-146a, miR-181c, miR-29b, and miR-342), and they were all shown to be down regulated in in iduals with AD compared to controls. Of these directionally concordant miRNAs, the strongest evidence was for miR-107 which has also been shown in previous studies to be involved in the dysregulation of proteins involved in aspects of AD pathology, as well as being consistently downregulated in studies of AD brains. We conclude that imperative to the discovery of reliable and replicable miRNA biomarkers of AD, standardised methods of measurements, appropriate statistical analysis, utilization of large datasets with machine learning approaches, and comprehensive reporting of findings is urgently needed.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.JAD.2022.02.062
Abstract: Considerable work exists in the literature to describe the negative impacts of early-life stress exposures on health in adulthood. This study investigated whether the accumulation of adverse childhood events is associated with later-life cognitive function and incident dementia. Participants were 1562 community-dwelling older adults, who were enrolled in the ESPRIT cohort in France. Adverse childhood events were measured using a modified version of the Childhood Trauma Questionnaire. Cognition was measured using tests of global cognition, visual memory, verbal fluency, psychomotor speed and executive function. Fourteen-year incident dementia was diagnosed using DSM-IV criteria. In comparison to participants with two or less adverse childhood events, increased risk of poor psychomotor speed at baseline was observed in in iduals with multiple adverse childhood events (3-4 events OR: 1.39, 95% CI: 1.00-1.93) ≥5 events (OR: 1.52, 95% CI: 1.07-2.17), particularly in women but not in men. Worse verbal fluency was also observed in in iduals who experienced between three and four adverse childhood events (OR: 1.34, 95% CI: 1.00-1.78). Amongst the in idual factors investigated, early-life abuse/maltreatment (OR: 1.47, 95% CI: 1.02-2.14) and poverty/financial difficulties (OR: 1.53, 95% CI: 1.12-2.08) was associated with worse psychomotor speed. No associations were observed with incident dementia. Participants most at risk (those with baseline dementia) were excluded. Multiple adverse childhood events are associated with worse psychomotor speed, and verbal fluency in later-life, however further research is needed to determine the mechanisms underlying this association and whether it results from unmeasured confounding, including social disadvantage.
Publisher: Elsevier BV
Date: 08-2004
Publisher: BMJ
Date: 04-2023
DOI: 10.1136/BMJOPEN-2022-069915
Abstract: The world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD). This paper presents the protocol for the STAtins in Reducing Events in the Elderly (STAREE) trial, a randomised double-blind placebo-controlled trial examining the effects of statins in community dwelling older people without CVD, diabetes or dementia. We will conduct a double-blind, randomised placebo-controlled trial among people aged 70 years and over, recruited through Australian general practice and with no history of clinical CVD, diabetes or dementia. Participants will be randomly assigned to oral atorvastatin (40 mg daily) or matching placebo (1:1 ratio). The co-primary endpoints are disability-free survival defined as survival-free of dementia and persistent physical disability, and major cardiovascular events (cardiovascular death or non-fatal myocardial infarction or stroke). Secondary endpoints are all-cause death, dementia and other cognitive decline, persistent physical disability, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, heart failure, atrial fibrillation, fatal and non-fatal cancer, all-cause hospitalisation, need for permanent residential care and quality of life. Comparisons between assigned treatment arms will be on an intention-to-treat basis with each of the co-primary endpoints analysed separately in time-to-first-event analyses using Cox proportional hazards regression models. STAREE will address uncertainties about the preventive effects of statins on a range of clinical outcomes important to older people. Institutional ethics approval has been obtained. All research outputs will be disseminated to general practitioner co-investigators and participants, published in peer-reviewed journals and presented at national and international conferences. NCT02099123 .
Publisher: Springer Science and Business Media LLC
Date: 06-11-2020
DOI: 10.1186/S12889-020-09639-9
Abstract: Quality of life (QoL) is multi-dimensional concept of an in idual’ general well-being status in relation to their value, environment, cultural and social context in which they live. This study aimed to quantitatively synthesise available evidence on the association between QoL and mortality in the general population. An electronic search was conducted using three bibliographic databases, MEDLINE, EMBASE and PsycINFO. Inclusion criteria were studies that assessed QoL using standardized tools and examined mortality risk in a non-patient population. Qualitative data synthesis and meta-analyses using a random-effects model were performed. Of 4184 articles identified, 47 were eligible for inclusion, involving approximately 1,200,000 participants. Studies were highly heterogeneous in terms of QoL measures, population characteristics and data analysis. In total, 43 studies (91.5%) reported that better QoL was associated with lower mortality risk. The results of four meta-analyses indicated that higher health-related QoL (HRQoL) is associated with lower mortality risk, which was consistent for overall HRQoL (HR 0.633, 95% CI: 0.514 to 0.780), physical function (HR 0.987, 95% CI: 0.982 to 0.992), physical component score (OR 0.950, 95% CI: 0.935 to 0.965), and mental component score (OR 0.980, 95% CI: 0.969 to 0.992). These findings provide evidence that better QoL/HRQoL was associated with lower mortality risk. The utility of these measures in predicting mortality risk indicates that they should be considered further as potential screening tools in general clinical practice, beyond the traditional objective measures such as body mass index and the results of laboratory tests.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
Publisher: Springer Science and Business Media LLC
Date: 22-10-2021
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.EURONEURO.2015.08.022
Abstract: A number of genome-wide association studies (GWAS) have investigated risk factors for major depressive disorder (MDD), however there has been little attempt to replicate these findings in population-based studies of depressive symptoms. Variants within three genes, BICC1, PCLO and GRM7 were selected for replication in our study based on the following criteria: they were identified in a prior MDD GWAS study a subsequent study found evidence that they influenced depression risk and there is a solid biological basis for a role in depression. We firstly investigated whether these variants were associated with depressive symptoms in our population-based cohort of 929 elderly (238 with clinical depressive symptoms and 691 controls), and secondly to investigate associations with structural brain alterations. A number of nominally significant associations were identified, but none reached Bonferroni-corrected significance levels. Common SNPs in BICC1 and PCLO were associated with a 50% and 30% decreased risk of depression, respectively. PCLO rs2522833 was also associated with the volume of grey matter (p=1.6×10(-3)), and to a lesser extent with hippoc al volume and white matter lesions. Among depressed in iduals rs9870680 (GRM7) was associated with the volume of grey and white matter (p=10(-4) and 8.3×10(-3), respectively). Our results provide some support for the involvement of BICC1 and PCLO in late-life depressive disorders and preliminary evidence that these genetic variants may also influence brain structural volumes. However effect sizes remain modest and associations did not reach corrected significance levels. Further large imaging studies are needed to confirm our findings.
Publisher: Springer Science and Business Media LLC
Date: 29-11-2016
DOI: 10.1038/TP.2016.234
Abstract: Yoga is associated with reduced stress and increased well-being, although the molecular basis for these benefits is not clear. Mounting evidence implicates the immune response, with current studies focused on protein immune markers (such as cytokines) in clinical populations. To explore the molecular impact, this pilot study uses a subs le ( n =28) from a randomised waitlist control trial investigating the impact of an 8-week yoga intervention in a community population of women reporting psychological distress ( N =116). We measured interleukin-6 (IL-6), tumour necrosis factor (TNF) and C-reactive protein (CRP) protein levels, and the DNA methylation of these genes and the global indicator, LINE-1 . Correlations between these and psychological variables were explored, identifying moderate correlations with CRP protein levels, and methylation of IL-6 , CRP and LINE-1 . Many cytokine s les were below detection, however a Mann–Whitney U demonstrated a trend of moderate between-group effect for elevated IL-6 in the yoga group. Methylation analyses applied cross-sectional and non-controlled longitudinal analyses. Waist-to-height ratio and age were covaried. We demonstrated reduced methylation of the TNF region in the yoga group relative to the waitlist control group. No other genes demonstrated a significant difference. Longitudinal analysis further supported these results. This study is one of the first to explore yoga and immunological markers in a non-clinical population, and is the first study to explore DNA methylation. These findings indicate that further research into molecular impact of yoga on markers of immune function is warranted, with larger studies required.
Publisher: Cambridge University Press (CUP)
Date: 02-2008
DOI: 10.1017/S1041610207006485
Abstract: A plethora of in vitro and in vivo studies have supported the neuroprotective role of estrogens and their impact on the neurotransmitter systems implicated in cognition. Recent hormonal replacement therapy (HRT) trials in non-demented postmenopausal women suggest a temporary positive effect (notably on verbal memory), and four meta-analyses converge to suggest a possible protective effect in relation to Alzheimer's disease (reducing risk by 29 to 44%). However, data from the only large randomized controlled trial published to date, the Women's Health Initiative Memory Study, did not confirm these observations and have even suggested an increase in dementia risk for women using HRT compared to controls. Apart from methodological differences, one key shortcoming of this trial has probably been the focus on late-onset (postmenopausal) hormonal changes, i.e. at a time when the neurodegenerative process has already begun and without taking into account in idual lifetime exposure to hormone variability. Multifactorial models based on an exhaustive view of all hormonal events throughout the reproductive life (rather than on a specific exposure to a given steroid) together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia.
Publisher: Bentham Science Publishers Ltd.
Date: 05-2021
DOI: 10.2174/1567205018666210823100721
Abstract: There is strong evidence that epigenetic age acceleration is associated with increased risk of later-life diseases and all-cause mortality. However, there is currently limited evidence that suggests accelerated epigenetic age is associated with dementia risk. This study aims to clarify whether epigenetic biomarkers of accelerated aging can predict dementia risk, which is an important consideration as aging is the greatest risk factor for the disease. DNA methylation was measured in peripheral blood s les provided by 160 participants from the ASPirin in Reducing Events in the Elderly study, including 73 pre-symptomatic dementia cases and 87 controls matched for age, sex, and smoking and education status. Epigenetic age was calculated using Horvath, Hannum, GrimAge and PhenoAge DNA methylation clocks, and age acceleration (the disparity between chronological age and epigenetic age) was determined. There was no difference in age acceleration between dementia cases and controls. In males, only Hannum’s intrinsic epigenetic age acceleration was increased in pre-symptomatic dementia cases compared to controls (Δ +1.8 years, p = 0.03). These findings provide no strong evidence that accelerated epigenetic aging measured in peripheral blood can predict dementia risk.
Publisher: Informa UK Limited
Date: 05-07-2018
Publisher: Springer Science and Business Media LLC
Date: 09-2012
DOI: 10.2165/11635960-000000000-00000
Abstract: Accumulating evidence suggests the involvement of estrogen in depression. Estrogen can modulate neurotransmitter turnover, enhancing the levels of serotonin and noradrenaline (norepinephrine), and it is involved in the regulation of serotonin receptor number and function. Across the female reproductive life, fluctuating estrogen levels and low levels have been associated with depressed mood and there is strong support for a beneficial effect of estrogen-containing hormone treatment in depressed peri-menopausal women. Estrogen exerts its biological effects in large part through intracellular activation of its principal receptors, estrogen receptor α (ESR1) and estrogen receptor β (ESR2). Genetic variation in the estrogen receptors may therefore modify estrogen signalling, thus influencing a woman's susceptibility to developing depression. This review provides a synthesis of studies that have examined the association between estrogen receptor polymorphisms and depression-related mood disorders across the lifetime. Studies were identified through a search of the literature from January 1980 until March 2012 using MEDLINE, Web of Knowledge, Cochrane Library and PsycINFO databases. The studies conducted to date have produced inconsistent findings, which likely relates to the large heterogeneity in terms of the populations, study design and depression measures used. It appears unlikely that the common ESR1 variants rs2234693 and rs9340799 are associated with moderate depressive symptoms in women however, there is some evidence that indicates a significant association with more severe depressive symptoms, major depressive disorder and anxiety. There are too few studies of ESR2 polymorphisms to draw any definite conclusions however, preliminary evidence suggests that specific variants may modify the risk of depression associated with the use of hormone treatment in women. Few studies have investigated associations in men, and they have focused almost exclusively on ESR1, but all report non-significant findings. Much work is therefore still needed in this field. If it is confirmed that specific estrogen receptor polymorphisms are associated with the risk of depression, this could have important preventive and therapeutic implications, with the potential to develop targeted estrogen receptor agonists and antagonists. Furthermore, it is possible that such therapies may be more effective in treating particular people with depression based on their genetic profile, which is an exciting prospect given that many people do not respond to current antidepressant treatments.
Publisher: Elsevier BV
Date: 12-2017
Publisher: American Chemical Society (ACS)
Date: 10-10-2007
DOI: 10.1021/JM0704550
Abstract: A series of ghrelin receptor ligands based on the trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the significance of the aminoisobutyryl (Aib) moiety, a common feature in numerous growth hormone secretagogues described in the literature. Potent agonist and antagonist ligands of the growth hormone secretagogue receptor type 1a (GHS-R1a) were obtained, i.e., compounds 41 (JMV2894) and 17 (JMV3031). The best compounds were evaluated for their in vivo activity on food intake, after sc injection in rodents. Among the tested compounds, few of them were able to stimulate food intake and some others, i.e., compounds 4 (JMV2959), 17, and 52 (JMV3021), acted as potent in vivo antagonist of hexarelin-stimulated food intake. These compounds did not stimulate growth hormone secretion in rats and furthermore did not antagonize growth hormone secretion induced by hexarelin, revealing that it is possible to modulate food intake without altering growth hormone secretion.
Publisher: Future Medicine Ltd
Date: 03-2017
Abstract: There is considerable interest in the potential nongenetic transmission of a suite of mental health conditions across generations, with epigenetics emerging as a candidate mediator of such effects. This review summarizes findings from 22 studies measuring candidate gene DNA methylation and seven epigenome-wide association studies of offspring epigenetic profile in women with adverse mental wellbeing measures (stress, depression or anxiety) in pregnancy. Despite some compelling evidence to suggest an association, there is a lack of reproducible findings, potentially linked to a number of limitations to this research and the field more broadly. Large cohorts with well characterized exposures across pregnancy are now needed. There is exciting potential that epigenetics may help explain some of the link between maternal wellbeing and child health outcomes, thereby informing novel interventions, but future studies must address current limitations to advance translational knowledge in this area.
Publisher: Springer Science and Business Media LLC
Date: 22-03-2021
Publisher: Wiley
Date: 07-09-2019
DOI: 10.1016/J.JALZ.2019.05.011
Abstract: In iduals with homozygosity for the apolipoprotein E (APOE) ε4 allele are in the highest risk category for late-onset Alzheimer's disease (LOAD). However, some in iduals in this category do not develop LOAD beyond the age of 75 years, despite being at elevated genetic risk. These "resilient" in iduals may carry protective genetic factors. This study aimed to systematically review any previous studies that involved resilient APOE ε4 homozygotes and to identify possible modifying or protective genetic factors. Fifteen studies met our inclusion criteria and reported genetic factors contributing to reduced risk. We found that only two single nucleotide polymorphisms, CASP7 rs10553596 and SERPINA3 rs4934-A/A, had strong evidence. We found a paucity of studies adequately designed to discover protective genetic factors against LOAD. Many studies combined APOE ε4 homozygotes and heterozygotes together because of small s le sizes and used control populations too young to be clearly defined as controls for LOAD.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2019
Publisher: Informa UK Limited
Date: 22-11-2014
DOI: 10.4161/EPI.27248
Publisher: Springer Science and Business Media LLC
Date: 25-05-2021
DOI: 10.1186/S13104-021-05616-6
Abstract: A feature of late-life depression is alterations of the stress hormone system. The CYP21A2 gene encodes for the steroid 21-hydroxylase enzyme which is required for the biosynthesis of mineralocorticoids and glucocorticoids, two main components of the stress response in humans. Variants in the CYP21A2 gene could influence risk of late-life depression, but this has not been examined. This study investigated possible associations between five variants in the CYP21A2 gene and late-life depression in 1007 older community-dwelling men and women. In multivariate logistic regression model, significant associations were found between three single-nucleotide polymorphisms ( rs389883 , rs437179 , and rs630379 ) and depression in women specifically (OR ranging from 1.51 to 1.68, p-values 0.025 to 0.0045), and the two latter remained significant after correction for multiple testing. Variants of the CYP21A2 gene appear as susceptibility factors for late-life depression in a sex-specific manner, independently of somatic and neuropsychiatric comorbidity.
Publisher: Springer Science and Business Media LLC
Date: 26-10-2021
DOI: 10.1007/S00228-021-03239-1
Abstract: Recent epidemiological evidence has suggested that use of lipid-lowering medications, particularly statins, was associated with reduced cardiovascular disease (CVD) events and persistent physical disability in healthy older adults. However, the comparative efficacy of different statins in this group remains unclear. This study aimed to compare different forms of statins in their associations with CVD and physical disability in healthy older adults. This post hoc analysis included data from 5981 participants aged ≥ 70 years (≥ 65 if US minorities median age:74.0) followed for a median of 4.7 years, who had no prior CVD events or physical disability and reported using a statin at baseline. The incidence of the composite and components of major adverse cardiovascular events and persistent physical disability were compared across different statins according to their type, potency, and lipophilicity using multivariable Cox proportional-hazards models. Atorvastatin was the most used statin type at baseline (37.9%), followed by simvastatin (29.6%), rosuvastatin (25.5%), and other statins (7.0%, predominantly pravastatin). In comparisons of specific statins according to type and lipophilicity (lipophilic vs. hydrophilic statin), observed differences in all outcomes were small and not statistically significant (all p values > 0.05). High-potency statin use (atorvastatin and rosuvastatin) was marginally associated with lower risk of fatal CVD events compared with low-/moderate-potency statin use (hazard ratio: 0.59 95% confidence interval: 0.35, 1.00). There were minimal differences in CVD outcomes and no significant difference in persistent physical disability between various forms of statins in healthy older adults. Future investigations are needed to confirm our results.
Publisher: CMA Joule Inc.
Date: 2019
DOI: 10.1503/JPN.180026
Publisher: Wiley
Date: 08-09-2022
DOI: 10.1111/ADD.15632
Abstract: Alcohol consumption is common in adolescence and young adulthood and may continue into pregnancy, posing serious risk to early fetal development. We examine the frequency of periconception alcohol use (prior to pregnancy awareness) and the extent to which adolescent and young adult alcohol use prospectively predict periconception use. A longitudinal, population‐based study. Victoria, Australia. A total of 289 women in trimester three of pregnancy (age 29–35 years 388 pregnancies). The main exposures were binge [≥ 4.0 standard drinks (SDs)/day] and frequent (≥ 3 days/week) drinking in adolescence (mean age = 14.9–17.4 years) and young adulthood (mean age 20.7–29.1 years). Outcomes were frequency (≥ 3 days/week, ≥ monthly, never) and quantity (≥ 4.0 SDs, ≥ 0.5 and 4.0 SDs, none) of periconception drinking. Alcohol use was common in young adulthood prior to pregnancy (72%) and in the early weeks of pregnancy (76%). The proportions drinking on most days and binge drinking were similar at both points. Reflecting a high degree of continuity in alcohol use behaviours, most women who drank periconceptionally had an earlier history of frequent (77%) and/or binge (85%) drinking throughout the adolescent or young adult years. Young adult binge drinking prospectively predicted periconception drinking quantity [odds ratio (OR) = 3.7, 95% confidence interval (CI) = 1.9–7.4], compared with women with no prior history. Similarly, frequent young adult drinking prospectively predicted frequent periconception drinking (OR = 30.7, 95% CI = 12.3–76.7). Women who engage in risky (i.e. frequent and binge) drinking in their adolescent and young adult years are more likely to report risky drinking in early pregnancy prior to pregnancy recognition than women with no prior history of risky drinking.
Publisher: Oxford University Press (OUP)
Date: 28-10-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-05-2012
Abstract: Despite evidence that estrogens may be involved in atherothrombosis, the role of endogenous sex steroid hormones in ischemic arterial disease among postmenopausal women remains uncertain. In the Three‐City prospective cohort study of subjects (n=9294) years of age, we investigated the association of total 17β‐estradiol, bioavailable 17β‐estradiol, and total testosterone with the 4‐year incidence of ischemic arterial disease among postmenopausal women who did not use any hormone therapy. We designed a case–cohort study including a random s le of 537 subjects and 106 incident cases of first cardiovascular events. Weighted Cox proportional‐hazards models with age as the time scale were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for ischemic arterial disease by a 1–standard deviation increase in sex steroid hormones. In univariate analysis, HR of ischemic arterial disease was positively and significantly associated with both total and bioavailable estradiol levels. These associations remained significant after adjustment for traditional cardiovascular risk factors, including body mass index, diabetes, hypercholesterolemia, hypertension, and smoking status (HR: 1.42, 95% CI: 1.12–1.79, P .01 and HR: 1.42, 95% CI: 1.12–1.78, P .01, respectively). Separate analysis for coronary heart disease yielded similar results (adjusted HR: 1.49, 95% CI: 1.10–2.02, P =0.01 and adjusted HR: 1.50, 95% CI: 1.11–2.04, P .01, respectively), and a borderline significant trend was observed for ischemic stroke (HR: 1.34, 95% CI: 0.95–1.89, P =0.08 and HR: 1.32, 95% CI: 0.94–1.84, P =0.11, respectively). By contrast, no significant association was found between total testosterone and ischemic arterial disease in both univariate and adjusted analyses. High plasma level of endogenous estradiol emerges as a new predictor of ischemic arterial disease in older postmenopausal women. ( J Am Heart Assoc . 2012 :e001388 doi : 10.1161/JAHA.112.001388 .)
Publisher: Elsevier BV
Date: 07-2022
Publisher: American Chemical Society (ACS)
Date: 15-01-2008
DOI: 10.1021/JM701292S
Abstract: Ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the replacement of the alpha-aminoisobutyryl moiety by aromatic or heteroaromatic groups. Compounds 5 and 34 acted as potent in vivo antagonists of hexarelin-stimulated food intake. These two compounds did not stimulate growth hormone secretion in rodents and did not antagonize growth hormone secretion induced by hexarelin.
Publisher: Oxford University Press (OUP)
Date: 04-2023
Abstract: Evidence for the prognostic implications of hyperglycaemia in older adults is inconsistent. To evaluate disability-free survival (DFS) in older in iduals by glycaemic status. This analysis used data from a randomised trial recruiting 19,114 community-based participants aged ≥70 years, who had no prior cardiovascular events, dementia and physical disability. Participants with sufficient information to ascertain their baseline diabetes status were categorised as having normoglycaemia (fasting plasma glucose [FPG] & 5.6 mmol/l, 64%), prediabetes (FPG 5.6 to & .0 mmol/l, 26%) and diabetes (self-report or FPG ≥ 7.0 mmol/l or use of glucose-lowering agents, 11%). The primary outcome was loss of disability-free survival (DFS), a composite of all-cause mortality, persistent physical disability or dementia. Other outcomes included the three in idual components of the DFS loss, as well as cognitive impairment-no dementia (CIND), major adverse cardiovascular events (MACE) and any cardiovascular event. Cox models were used for outcome analyses, with covariate adjustment using inverse-probability weighting. We included 18,816 participants (median follow-up: 6.9 years). Compared to normoglycaemia, participants with diabetes had greater risks of DFS loss (weighted HR: 1.39, 95% CI 1.21–1.60), all-cause mortality (1.45, 1.23–1.72), persistent physical disability (1.73, 1.35–2.22), CIND (1.22, 1.08–1.38), MACE (1.30, 1.04–1.63) and cardiovascular events (1.25, 1.02–1.54) but not dementia (1.13, 0.87–1.47). The prediabetes group did not have an excess risk for DFS loss (1.02, 0.93–1.12) or other outcomes. Among older people, diabetes was associated with reduced DFS, and higher risk of CIND and cardiovascular outcomes, whereas prediabetes was not. The impact of preventing or treating diabetes in this age group deserves closer attention.
Publisher: Future Medicine Ltd
Date: 12-2021
Abstract: Background: Binge-level prenatal alcohol exposure (PAE) causes developmental abnormalities, which may be mediated in part by epigenetic mechanisms. Despite this, few studies have characterised the association of binge PAE with DNA methylation in offspring. Methods: We investigated the association between binge PAE and genome-wide DNA methylation profiles in a sex-specific manner in neonatal buccal and placental s les. Results: We identified no differentially methylated CpGs or differentially methylated regions (DMRs) at false discovery rate .05. However, using a sum-of-ranks approach, we identified a DMR in each tissue of female offspring. The DMR identified in buccal s les is located near regions with previously-reported associations to fetal alcohol spectrum disorder (FASD) and binge PAE. Conclusion: Our findings warrant further replication and highlight a potential epigenetic link between binge PAE and FASD.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.PSYNEUEN.2017.11.003
Abstract: Depression is one of the most prevalent psychiatric disorders, and in older persons is associated with high levels of comorbidity and under-treatment. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) stress axis is consistently observed in the older population as well as depressed patients, with the angiotensin converting enzyme (ACE) a key regulator of the stress response. Epigenetic regulation of ACE may play an important role in HPA axis (dys)regulation. To investigate ACE promoter methylation as a biomarker of late-life depression, and its association with genetic variation and cortisol secretion. The longitudinal general population ESPRIT study is aimed at investigating psychiatric disorders in older persons (n=1863, average age=73). Depression was assessed using the Mini International Neuropsychiatric Interview according to DSM-IV criteria and the Centre for Epidemiologic Studies Depression Scale (CES-D). Genotype information for seven polymorphisms across the ACE gene was also available. Blood and saliva s les collected at baseline and used to extract DNA and measure cortisol, respectively. Sequenom MassARRAY was used to measure promoter DNA methylation of the ACE gene (n=552). There was no evidence of an association between ACE promoter methylation and depression. However, there was evidence that ACE genetic variants influenced methylation, and modified the association between depression and methylation (Δ at various sites -2.05% to 1.74% p=0.019 to 0.039). Multivariate analyses were adjusted for participants' lifestyle, health and medical history. Independent of depression status, ACE methylation was inversely correlated with cortisol levels (r=-0.336, p=0.042). This study provides evidence that associations between ACE methylation and depression are genotype-dependent, suggesting that the development of reliable depression biomarkers may need to consider methylation levels in combination with underlying genetic variation. ACE methylation may also be a suitable biomarker of cortisol and/or HPA axis activity.
Publisher: Future Medicine Ltd
Date: 11-2016
Abstract: Certain in iduals are more susceptible to stress and trauma, as well as the physical and mental health consequences following such exposure, including risk for post-traumatic stress disorder (PTSD). This differing vulnerability is likely to be influenced by genetic predisposition and specific characteristics of the stress itself (nature, intensity and duration), as well as epigenetic mechanisms. In this review we provide an overview of research findings in this field. We highlight some of the key genetic risk factors identified for PTSD, and the evidence that epigenetic processes might play a role in the biological response to trauma, as well as being potential biomarkers of PTSD risk. We also discuss important considerations for future research in this area.
Publisher: Wiley
Date: 09-11-2012
Publisher: Wiley
Date: 14-03-2013
DOI: 10.1016/J.JALZ.2012.12.008
Abstract: Genetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors. The association between five ESR α (ESR1) and β (ESR2) polymorphisms with 7-year dementia incidence was examined among 6959 older men and women from the Three City Study using multivariate-adjusted Cox regression models with delayed entry. Gender, the apolipoprotein E (APOE) ε4 allele, and hormone treatment were considered as potential effect modifiers of this association. Among women, the CC genotype of ESR1rs2234693 was specifically associated with a small increased risk of AD (adjusted hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.03-2.28, P = .03). However, women with this genotype had a substantially increased risk of AD associated with the APOE ε4 allele (adjusted HR: 3.24, 95% CI: 1.81-5.79 for women rs2234693 CC compared with HR: 1.87, 95% CI: 1.37-2.56 for all women). There was also evidence of a nominally significant interaction between the ESR1 and ESR2 polymorphisms on the risk of all dementias (P = .04). Hormone treatment did not modify these associations, and there were no significant associations in men. Although there was only weak support for a gender-specific association between the common ESR1rs2234693 polymorphism and AD, this polymorphism may act as an effect modifier, modifying the association between an ESR2 polymorphism and dementia, as well as the risk of AD associated with the APOE ε4 allele.
Publisher: Research Square Platform LLC
Date: 06-10-2020
DOI: 10.21203/RS.3.RS-84994/V1
Abstract: Background Frailty is associated with multiple adverse health outcomes, including mortality. Several methods have been used to characterize frailty, each based on different frailty scales. These include scales based on a phenotype, multidomain, and deficit accumulations. Several systematic reviews have examined the association between frailty and mortality however, it is unclear whether these different frailty scales similarly predict mortality. This umbrella review aims to examine the association between frailty assessed by different frailty scales and all-cause mortality among community-dwelling older adults. Methods The umbrella review protocol was registered at PROSPERO, and it was conducted following the PRISMA statement. MEDLINE, Embase, PubMed, Cochrane Database of Systematic Reviews, Joanna Briggs Institute (JBI) EBP database, and Web of Science database was searched to identify systematic reviews and meta-analyses examining the association between frailty and all-cause mortality. Methodological quality was assessed using the JBI. Critical Appraisal Checklist and online AMSTAR-2 critical appraisal checklist. For eligible studies, essential information was extracted and synthesized qualitatively. Results Five systematic reviews were included, with a total of 434,115 participants. Three systematic reviews focused on single frailty scales one evaluated Fried physical frailty phenotype and its modifications another focused on the deficit accumulation frailty index. The third evaluated the FRAIL (Fatigue, Resistance, Ambulation, Illness, and Loss of weight) scale. The two other systematic reviews determined the association between frailty and mortality using different frailty scales. All the systematic reviews performed meta-analyses and assessed between-study heterogeneity. All of the systematic reviews found that frailty was significantly associated with all-cause mortality. Conclusion This umbrella review demonstrates that frailty is a significant predictor of all-cause mortality, irrespective of the specific frailty scale.
Publisher: Cambridge University Press (CUP)
Date: 04-04-2016
DOI: 10.1017/S0954579416000183
Abstract: Maternal mental health during pregnancy has been linked to health outcomes in progeny. Mounting evidence implicates fetal “programming” in this process, possibly via epigenetic disruption. Maternal mental health has been associated with glucocorticoid receptor methylation (nuclear receptor subfamily 3, group C, member 1 [ NR3C1 ]) in the neonate however, most studies have been small ( n 100) and have failed to control for multiple testing in the statistical analysis. The Barwon Infant Study is a population-derived birth cohort with antenatal recruitment. Maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale and psychological distress using the Perceived Stress Scale. NR3C1 cord blood methylation levels were determined using Sequenom MassArray for 481 participants. Maternal psychological distress and anxiety were associated with a small increase in neonate NR3C1 methylation at specific CpG sites, thus replicating some previous findings. However, associations were only nominally significant and did not remain after correction for the number of CpG sites and exposures investigated. As the largest study to explore the relationship between maternal well-being and offspring NR3C1 cord blood methylation, our results highlight the need for caution when interpreting previous findings in this area. Future studies must ensure they are adequately powered to detect the likely small effect sizes while controlling for multiple testing.
Publisher: Springer Science and Business Media LLC
Date: 25-01-2017
DOI: 10.1038/SREP41140
Abstract: Rs1344706 in the the zinc finger protein 804A ( ZNF804A ) gene has been identified to be associated with schizophrenia and bipolar disorder (BD) in Europeans. However, whether rs1344706 is associated with schizophrenia in Chinese populations remains inconclusive furthermore, the association between rs1344706 and BD in Chinese populations has been rarely explored. To explore the association between rs1344706 and schizophrenia/BD in Chinese populations, we genotyped rs1344706 among 1128 Chinese subjects (537 patients with BD and 591 controls) and found that r s1344706 showed marginal allelic association with BD ( P = 0.028) with T-allele being more prevalent in cases than that in controls (OR = 1.19, 95% CI 1.03–1.37). Meta-analysis of rs1344706 by pooling all available data showed that rs1344706 was significantly associated with BD ( P = 0.001). Besides, positive association of rs1344706 with schizophrenia was observed in Northern Chinese ( P = 0.005). Furthermore, ZNF804A is highly expressed in human and mouse brains, especially in prenatal stage.
Publisher: MDPI AG
Date: 17-08-2023
Abstract: Severe or chronic stress and trauma can have a detrimental impact on health. Evidence suggests that early-life adversity can become biologically embedded and has the potential to influence health outcomes decades later. Epigenetics is one mechanism that has been implicated in these long-lasting effects. Observational studies in humans indicate that the effects of stress could even persist across generations, although whether or not epigenetic mechanisms are involved remains under debate. Here, we provide an overview of studies in animals and humans that demonstrate the effects of early-life stress on DNA methylation, one of the most widely studied epigenetic mechanisms, and summarize findings from animal models demonstrating the involvement of epigenetics in the transmission of stress across generations. We then describe the results of a scoping review to determine the extent to which the terms intergenerational or transgenerational have been used in human studies investigating the transmission of trauma and stress via epigenetic mechanisms. We end with a discussion of key areas for future research to advance understanding of the role of epigenetics in the legacy effects of stress and trauma.
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.PSYNEUEN.2011.04.011
Abstract: Estrogen is thought to play a key role in anxiety, but it remains unknown whether genetic variants in the estrogen receptors (ERs) can influence the risk of anxiety. This study investigated whether ESR1 and ESR2 gene variants were associated with specific anxiety disorders in postmenopausal women and evaluated the potential modifying effect of hormone treatment (HT) on these associations. One thousand and ninety-two community-dwelling women aged 65 years and older were recruited as part of the ESPRIT Study in Montpellier, France. Anxiety was assessed using the Mini-International Neuropsychiatry Interview (MINI), according to DSM-IV criteria. Two ESR1 and three ESR2 polymorphisms were genotyped. The most common anxiety disorders were phobia (14.2%) and generalised anxiety disorder (GAD, 8%). The A allele of ESR2 rs1256049 was associated with an increased risk of GAD [OR: 2.06, 95% CI: 1.09-3.87], while both ESR1 polymorphisms were specifically associated with phobia. The C allele of ESR1 rs2234693 decreased the risk of phobia by 42% [95% CI: 0.41-0.83], and this remained significant even after Bonferroni correction. The G allele of ESR1 rs9340799 was associated with a 31% decreased phobia risk [95% CI: 0.49-0.96]. There was also evidence of a significant gene-environment interaction, where only women who were currently using HT had a reduced risk of phobia with these ESR1 gene variants. This study confirms earlier findings of an association between ESR1 and global anxiety in older women, however these associations varied depending on the anxiety syndrome and the use of HT. The results also suggest that the ESR2 may contribute to the genetic vulnerability to GAD, but these findings require further confirmation.
Publisher: Wiley
Date: 16-11-2021
DOI: 10.1002/GPS.5644
Abstract: Poor social health is prevalent in older adults and may be associated with worse cognition, and increased dementia risk. The aim of this study was to determine whether social isolation, social support and loneliness are independently associated with cognitive function and incident dementia over 5 years in older adults, and to investigate potential gender differences. Participants were 11,498 community‐dwelling relatively healthy Australians aged 70–94, in the ASPREE Longitudinal Study of Older Persons (ALSOP). Social isolation, social support, loneliness and cognitive function were assessed through self‐report. Outcomes examined were cognitive decline ( .5 SD decline in cognitive performance since baseline) and incident dementia (adjudicated according to DSM‐IV criteria). Most participants self‐reported good social health (92%) with very few socially isolated (2%), with low social support (2%) or lonely (5%). Among women, social isolation and low social support were consistently associated with lower cognitive function (e.g., social support and cognition β = −1.17, p 0.001). No consistent longitudinal associations were observed between baseline social health and cognitive decline (over median 3.1 years) or incident dementia (over median 4.4 years social isolation: HR = 1.00, p = 0.99 low social support: HR = 1.79, p = 0.11 loneliness: HR = 0.72, p = 0.34 among women and men). Our study provides evidence that social isolation and a low social support are associated with worse cognitive function in women, but not men. Social health did not predict incident cognitive decline or dementia, but we lacked power to stratify dementia analyses by gender.
Publisher: Oxford University Press (OUP)
Date: 02-2007
Abstract: The expression pattern of tight junction (TJ) proteins is frequently disrupted in epithelial tumors. In particular, isoform- and organ-specific alterations of claudins have been detected in human cancers, highlighting them as interesting tools for the prognosis or treatment of various carcinomas. However, the molecular mechanisms responsible for these alterations are seldom identified. Here, we analyzed the expression and localization of claudins 1, 4, and 7 in human bladder carcinoma. Claudin-4 expression was significantly altered in 26/39 tumors, contrasting with the rare modifications detected in the expression of claudins 1 and 7. Overexpression of claudin-4 in differentiated carcinomas was followed by a strong downregulation in invasive/high-grade tumors, and this expression pattern was associated to the 1-year survival of bladder tumor patients. A CpG island was identified within the coding sequence of the CLDN4 gene, and treatment with a methyl-transferase inhibitor restored expression of the protein in primary cultures prepared from high-grade human bladder tumors. In addition, claudin-4 expression correlated with its gene methylation profile in healthy and tumoral bladders from 20 patients, and downregulation of claudin-4 expression was detected in the urothelium of mice overexpressing DNA methyl transferase 3a (Dnmt3a). Delocalization of claudins 1 and 4 from TJs was observed in most human bladder tumors and in the bladder tumor cell line HT-1376. Although the CLDN4 gene was unmethylated in these cells, pharmacological inhibition of methyl transferases re-addressed the two proteins to TJs, resulting in an increase of cell polarization and transepithelial resistance. These biological effects were prevented by expression of claudin-4-specific siRNAs, demonstrating the important role played by claudin-4 in maintaining a functional regulation of homeostasis in urothelial cells. Results of this study indicate that the TJ barrier is disrupted from early stages of urothelial tumorigenesis. In addition, we identified hypermethylation as the mechanism leading to the alteration of claudin-4 expression, and maybe also localization, in bladder carcinoma.
Publisher: Future Medicine Ltd
Date: 12-2020
Abstract: Aim: To investigate whether genes implicated in dementia pathogenesis are differently methylated in peripheral blood. Materials & methods: Participants included 160 cognitively healthy in iduals aged 70+ years: 73 who were subsequently diagnosed with dementia and 87 controls matched on age, gender, education, smoking and baseline cognition. A total of 49 participants also provided blood s les at diagnosis. Blood DNA methylation of APOE, APP, BDNF, PIN1, SNCA and TOMM40 was examined. Results: A total of 56 of 299 probes were differentially methylated in dementia compared with controls and 39 probes prior to diagnosis. The greatest effect size was in APP (cg19423170, Δ-8.32%, adjusted p = 0.009 at diagnosis cg19933173, Δ-4.18%, adjusted p 0.0001 prediagnosis). Conclusion: Genes implicated in dementia pathogenesis show differential blood methylation in dementia, even prior to diagnosis.
Publisher: Oxford University Press (OUP)
Date: 02-08-2021
Abstract: Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterize a 67-item deficit-accumulation frailty index (FI) in 19 110 community-dwelling in iduals in the ASPirin in Reducing Events in the Elderly clinical trial. Participants aged 65–98 years were recruited from the United States and Australia and were without diagnosed dementia and cardiovascular disease, and major physical disability. The median FI score was .10 (interquartile range: .07–.14) at baseline, and the prevalence of frailty (FI & .21) increased from 8.1% to 17.4% after 6 years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r = −.31) and grip strength (r = −.46), and strongly associated with a modified Fried’s frailty phenotype (p & .0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (hazard ratio: 21.3, 95% confidence interval: 15.6–28.9). It added significantly to the predictive capacity of these outcomes above age, sex, and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older in iduals and provides important information about an in idual’s vulnerability to and risk of disease.
Publisher: Wiley
Date: 26-05-2021
DOI: 10.1111/ACEL.13384
Abstract: Few studies have measured the effect of genetic factors on dementia and cognitive decline in healthy older in iduals followed prospectively. We studied cumulative incidence of dementia and cognitive decline, stratified by APOE genotypes and polygenic risk score (PRS) tertiles, in 12,978 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrolment, participants had no history of diagnosed dementia, cardiovascular disease, physical disability or cognitive impairment. Dementia (adjudicated trial endpoint) and cognitive decline, defined as a .5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence for all‐cause dementia and cognitive decline was calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non‐ APOE variants. During a median 4.5 years of follow‐up, 324 participants developed dementia, 503 died. Cumulative incidence of dementia to age 85 years was 7.4% in all participants, 12.6% in APOE ε3/ε4 and 26.6% in ε4/ε4. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3‐fold increased dementia risk and 1.4/1.8‐fold cognitive decline risk, versus ε3/ε3 ( p 0.001 for both). High PRS tertile was associated with a 1.4‐fold dementia risk versus low (CI 1.04–1.76, p = 0.02), but was not associated with cognitive decline (CI 0.96–1.22, p = 0.18). Incidence of dementia among healthy older in iduals is low across all genotypes however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not.
Publisher: Springer Science and Business Media LLC
Date: 07-09-2016
DOI: 10.1038/SREP32687
Abstract: Previous studies have investigated the association between common variants in FKBP5 and MDD however, the results remain inconsistent. In order to conduct a comprehensive meta-analysis of the association between FKBP5 variants and MDD risk, seven studies involving 26582 subjects, including 12491 cases with MDD and 14091 controls, were enrolled totally. Four common SNPs (rs1360780, rs4713916, rs3800373 and rs755658) with complete data from two or more studies were analyzed. In the total s le, there was no evidence of a significant association between MDD and any of the four SNPs using a random-effects model. However, after removing one heterogeneous German study, as indicated by sensitivity analysis, both the rs1360780 T-allele (Z = 2.95, P = 0.003, OR = 1.06, 95% CI = 1.02–1.11) and the rs3800373 C-allele (Z = 3.05, P = 0.002, OR = 1.07, 95% CI 1.02–1.12) were significantly associated with MDD in a fixed-effect model. Our study thus provides support for an association between specific FKBP5 genetic variants and MDD risk. Rs4713916 was not significantly associated with MDD However, this analysis had limited statistical power and larger s le sizes are required to further validate this result. Future research should also investigate possible gender- and ethnicity-specific differences in the association between FKBP5 and MDD.
Publisher: Oxford University Press (OUP)
Date: 07-11-2020
Abstract: there may be age-related differences in the impact of weight change on health. This study systematically reviewed the evidence on the relationship between weight change and all-cause mortality in adults aged 65 years and older. MEDLINE, EMBASE and CINAHL were searched from inception to 11 June 2020, PROSPERO CRD 42019142268. We included observational studies reporting on the association between weight change and all-cause mortality in older community-dwelling adults. A random-effects meta-analysis was performed to calculate pooled hazard ratios and scored based on the Agency for Healthcare Research and Quality guidelines. a total of 30 studies, including 1,219,279 participants with 69,255 deaths, demonstrated that weight loss was associated with a 59% increase in mortality risk (hazard ratio (HR): 1.59 95% confidence interval (CI): 1.45–1.74 P & 0.001). Twenty-seven studies that reported outcomes for weight gain (1,210,116 participants with 65,481 deaths) indicated that weight gain was associated with a 10% increase in all-cause mortality (HR: 1.10 95%CI: 1.02, 1.17 P = 0.01). Four studies investigated weight fluctuation (2,283 events among 6,901 participants), which was associated with a 63% increased mortality risk (HR: 1.66 95%CI: 1.28, 2.15). No evidence of publication bias was observed (all P & 0.05). for community-dwelling older adults, weight changes (weight loss, gain or weight fluctuation) are associated with an increased risk of all-cause mortality risk relative to stable weight. Further research is needed to determine whether these associations vary depending upon initial weight, and whether or not the weight loss/gain was intentional.
Publisher: Oxford University Press (OUP)
Date: 10-11-2021
Abstract: Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. In the United States and Australia, 19 114 community-dwelling in iduals aged ≥70 and older (U.S. minorities ≥65 years) and free of overt cardiovascular disease, persistent physical disability, and dementia were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100-mg daily aspirin versus placebo. Frailty, a prespecified study end point, was defined according to a modified Fried frailty definition (Fried frailty) and the frailty index based on the deficit accumulation model (frailty index). Competing risk Cox proportional hazard models were used to compare time to incident frailty by aspirin versus placebo. Sensitivity analysis was conducted to include frailty data with and without imputation of missing data. Over a median 4.7 years, 2 252 participants developed incident Fried frailty, and 4 451 had incident frailty according to the frailty index. Compared with placebo, aspirin treatment did not alter the risk of incident frailty (Fried frailty hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.96−1.13 frailty index HR: 1.03, 95% CI 0.97−1.09). The proportion of in iduals classified as frail, and the trajectory in continuous frailty scores over time, were not different between the aspirin and placebo treatment groups. The results were consistent across a series of subgroups. Low-dose aspirin use in healthy older adults when initiated in older ages does not reduce risk of incident frailty or the trajectory of frailty.
Publisher: MDPI AG
Date: 29-06-2023
DOI: 10.3390/GERIATRICS8040071
Abstract: Objective: To identify the socio-demographic, lifestyle, and clinical characteristics associated with self-reported weight status in early (age 18 years) and late (age ≥ 70 years) adulthood. Methods: The number of participants was 11,288, who were relatively healthy community-dwelling Australian adults aged ≥70 years (mean age 75.1 ± 4.2 years) in the Aspirin in Reducing Events in the Elderly (ASPREE) Longitudinal Study of Older Persons (ALSOP) sub-study. Self-reported weight at the study baseline (age ≥ 70 years) and recalled weight at age 18 years were collected. Height measured at baseline was used to calculate the BMI at both time points. In iduals were categorised into one of five ‘lifetime’ weight status groups: healthy weight (at both age 18 year and ≥70 years), overweight (at either or both times), non-obese (age 18 year) to obesity (age ≥70 years), obesity (age 18 years) to non-obese (age ≥ 70 years), and early and later life obesity (at age 18 years and ≥70 years). Results: Participants who experienced obesity in early and/or late adulthood were at a higher risk of adverse clinical characteristics. Obesity in late adulthood (regardless of early adulthood weight status) was associated with high proportions of hypertension, diabetes, and dyslipidaemia, whereas obesity in early adulthood (regardless of late adulthood weight status) was associated with lower cognitive scores (on all four measures). Discussion/Conclusion: Healthy or overweight weight status in early and later adulthood was associated with more favourable socioeconomic, lifestyle, and clinical measures. Obesity in early adulthood was associated with lower cognitive function in later adulthood, whereas obesity in later adulthood was associated with hypertension, diabetes, and dyslipidaemia.
Publisher: Springer Science and Business Media LLC
Date: 05-11-2013
DOI: 10.1038/TP.2013.95
Publisher: Springer Science and Business Media LLC
Date: 07-2019
Publisher: Wiley
Date: 25-01-2017
DOI: 10.1002/MPR.1558
Publisher: Hindawi Limited
Date: 15-11-2019
DOI: 10.1002/DA.22974
Abstract: Sex differences in psychiatric disorders are common and could involve sex steroids. Aromatase, the product of the CYP19A1 gene, is the key enzyme in the conversion of androgen to estrogen. Whether CYP19A1 variants could be associated with depression differently in men and women has not been examined. This population-based study included 405 men and 602 women aged ≥65 years. A clinical level of depression (DEP) was defined as having a score ≥16 on the Center for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) spanning the CYP19A1 gene were genotyped and circulating levels of estradiol and testosterone were determined. Multivariable analyses were adjusted for age, body mass index, ischemic pathologies, cognitive impairment, and anxiety. Five SNPs were associated with DEP in women specifically and this varied according to a history of major depression (p-values .01 to .0005). Three SNPs were associated with an increased risk of late-life DEP in women without a history of major depression, while two SNPs were associated with a decreased DEP risk in women with a history of major depression and were also associated with higher estradiol levels. Variants of the CYP19A1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner. The polymorphisms decreasing the risk of recurrent depression in postmenopausal women also influence estradiol levels.
Publisher: S. Karger AG
Date: 2018
DOI: 10.1159/000490560
Abstract: b i Background: /i /b The ability to engage in sexual activity and better cognitive functioning are both associated with better health. However, the association between cognitive functioning and sexual activity is understudied. b i Objective: /i /b To examine the association between cognitive functioning with sexual activity and physical tenderness among community-dwelling older adults. b i Methods: /i /b From the Rotterdam Study, cognitive impairment and sexual activity were assessed in 4,201 community-dwelling, 60+ year olds between 2008 and 2014 in the Netherlands. Mild cognitive impairment (MCI) was based upon subjective complaints related to age and education-adjusted test scores. Mini-Mental State Examination (MMSE) impairment was defined by a score of & #x3c 26. Sexual activity and physical tenderness (e.g., fondling or kissing) in the last 6 months were assessed at an interview. Analyses were stratified by gender and partner status, with prevalence rates for the “no impairment” categories weighted based on age from the cognitive impairment categories. Inter-rater reliability was examined utilising 74 cohabiting couples of opposite gender. b i Results: /i /b It was found that 14% were categorised as having cognitive impairment, and & #x3c 1% as dementia (excluded from subsequent analyses). There was strong evidence that the odds of engaging in physical tenderness (observed through MMSE & #x3c 26, OR 2.14, 95% CI 1.32–3.48, i /i = 0.002) and sexual activity (MCI, OR 2.36, 95% CI 1.35–4.12, i /i = 0.003) among partnered females with no impairment was twice that observed among cognitively impaired partnered females. There was weak evidence that the odds of engaging in physical tenderness (MMSE & #x3c 26, OR 1.59, 95% CI 1.04–2.42, i /i = 0.03) and sexual activity (MMSE & #x3c 26, OR 1.51, 95% CI 1.02–2.24, i /i = 0.04) among partnered males with no impairment was 50% greater than observed among cognitively impaired partnered males. The associations between cognitive functioning and physical tenderness continued to remain after adjustment for physical function, diabetes, cardiovascular disease and cancer. There was no clear evidence of a difference between amnestic and non-amnestic MCI for sexual behaviour. There was moderate to substantial agreement among the coupled adults who had 1 partner categorised with MCI. b i Conclusion: /i /b Having no cognitive impairment was associated with more engagement in sexual activity and physical tenderness among community-dwelling older adults. Sexuality is an important aspect of active aging and our findings illustrate a potential barrier to maintaining or instigating intimate relationships as we age. Longitudinal analyses are required to explore the direction of effect.
Publisher: Springer Science and Business Media LLC
Date: 19-09-2017
DOI: 10.1038/MP.2017.195
Publisher: American Chemical Society (ACS)
Date: 22-03-2007
DOI: 10.1021/JM070024H
Abstract: A new series of growth hormone secretagogue (GHS) analogues based on the 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and their ability to stimulate intracellular calcium release to the cloned hGHS-1a ghrelin receptor expressed in LLC PK-1 cells. We have synthesized potent ligands of this receptor, some of them behaving as agonists, partial agonists, or antagonists. Some compounds among the most potent, i.e., agonist 29c (JMV2873), partial agonists including 21b (JMV2810), antagonists 19b (JMV2866) and 19c (JMV2844), were evaluated for their in vivo activity on food intake, after sc injection in rodents. Some compounds were found to stimulate food intake like hexarelin some others were identified as potent hexarelin antagonists in this assay. Among the tested compounds, 21b was identified as an in vitro ghrelin receptor partial agonist, as well as a potent in vivo antagonist of hexarelin-stimulated food intake in rodents. Compound 21b was without effect on GH release from rat. However, in this series of compounds, it was not possible to find a clear correlation between in vitro and in vivo results.
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.NEUROBIOLAGING.2013.09.026
Abstract: Structural imaging studies suggest gender differences in brain volumes however, whether hormone treatment (HT) can protect against age-related structural changes remains unknown, and no prior neuroimaging study has investigated potential interactions between HT and estrogen receptor (ESR) polymorphisms. Magnetic resonance imaging was used to measure gray and white matter, hippoc al volume, corpus callosum, cerebrospinal fluid (CSF), total intracranial volume (ICV) and white matter lesions (WML) in 582 non-demented older adults. In multivariable analysis, when compared to women who had never used HT, men and women currently on treatment, but not past users, had significantly smaller ratios of gray matter to ICV and increased atrophy (CSF/ICV ratio). Hippoc al and white matter volume as well as the corpus callosum area were not significantly different across groups. ESR2 variants were not significantly associated with brain measures, but women with the ESR1 rs2234693 C allele had significantly smaller WML. Furthermore this association was modified by HT use. Our results do not support a beneficial effect of HT on brain volumes in older women, but suggest the potential involvement of ESR1 in WML.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2020
DOI: 10.1161/HYPERTENSIONAHA.120.16209
Abstract: High office blood pressure variability (OBPV) in midlife increases the risk of cardiovascular disease (CVD), but the impact of OBPV in older adults without previous CVD is unknown. We conducted a post hoc analysis of ASPREE trial (Aspirin in Reducing Events in the Elderly) participants aged 70-years and older (65 for US minorities) without history of CVD events at baseline, to examine risk of incident CVD associated with long-term, visit-to-visit OBPV. CVD was a prespecified, adjudicated secondary end point in ASPREE. We estimated OBPV using within-in idual SD of mean systolic BP from baseline and first 2 annual visits. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% CI for associations with CVD events. In 16 475 participants who survived to year 2 without events, those in the highest tertile of OBPV had increased risk of CVD events after adjustment for multiple covariates, when compared with participants in the lowest tertile (HR, 1.36 [95% CI, 1.08–1.70] P =0.01). Similar increased risk was observed for ischemic stroke (HR, 1.56 [95% CI, 1.04–2.33] P =0.03), heart failure hospitalization, or death (HR, 1.73 [95% CI, 1.07–2.79] P =0.02), and all-cause mortality (HR, 1.27 [95% CI, 1.04–1.54] P =0.02). Findings were consistent when stratifying participants by use of antihypertensive drugs, while sensitivity analyses suggested the increased risk was especially for in iduals whose BP was uncontrolled during the OBPV estimation period. Our findings support increased OBPV as a risk factor for CVD events in healthy older adults with, or without hypertension, who have not had such events previously. URL: www.clinicaltrials.gov Unique identifiers: NCT01038583 URL: www.isrctn.com Unique identifiers: ISRCTN83772183.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-07-2023
Publisher: Oxford University Press (OUP)
Date: 12-2016
DOI: 10.1093/EEP/DVW023
Publisher: Wiley
Date: 03-06-2016
DOI: 10.1002/AJMG.B.32466
Abstract: Major depressive disorder (MDD) is one of the most common psychiatric disorders with a relatively high heritability (35-40%). Though rs1006737 in the CACNA1C gene showed significant association with MDD in a British large-scale candidate association study, most of the replication analyses with relatively small s le size reported negative association. Moreover, this locus has never been identified in previous genome-wide association studies (GWAS) for MDD. Here, we conducted a comprehensive meta-analysis of the association between CACNA1C variants and MDD risk by combining all published data. Genetic data from one European GWAS and five in idual follow-up studies, which include up to 12,629 patients of MDD and 28,653 controls, that is, the largest s le size on CACNA1C to date, were collected. Rs1006737 showed significant association with MDD in the fixed-effect model (Z = 2.56, P = 0.011, OR = 1.08, 95%CI = 1.04-1.12) and the association remained after reanalyzing the data according to ethnicity. We additionally analyzed other 25 SNPs, genotyped in only one replication study, across the CACNA1C locus, and found that two SNPs, rs4765905 (P = 0.041, OR = 1.05, 95%CI 1.00-1.09) and rs4765937 (P = 0.025, OR = 1.05, 95%CI 1.01-1.09) showed nominal association with MDD, while rs2239073 (P = 0.002, OR = 1.07, 95%CI 1.02-1.11) exhibited significant association with MDD, which survived from multiple corrections. Our study provides support for positive association between CACNA1C and MDD however, the current data suggest the necessity of replication analyses in a larger-scale s le. © 2016 Wiley Periodicals, Inc.
Start Date: 06-2016
End Date: 06-2020
Amount: $453,000.00
Funder: Australian Research Council
View Funded Activity