ORCID Profile
0000-0003-2036-7187
Current Organisations
Ollscoil na Gaillimhe – University of Galway
,
Monash University
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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: 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: 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: 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: BMJ
Date: 24-03-2017
Publisher: Informa UK Limited
Date: 27-04-2017
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: 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: Massachusetts Medical Society
Date: 18-10-2018
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: Elsevier BV
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 10-2014
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: Springer Science and Business Media LLC
Date: 04-09-2018
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: Wiley
Date: 08-11-2017
Publisher: Springer Science and Business Media LLC
Date: 29-05-2018
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: 2018
Publisher: Informa UK Limited
Date: 27-06-2020
Publisher: Springer Science and Business Media LLC
Date: 14-05-2019
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: 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: Springer Science and Business Media LLC
Date: 18-08-2018
DOI: 10.1007/S11356-018-2895-0
Abstract: Fruit shell residue from Xanthoceras sorbifolia was investigated as a potential biosorbent to remove crude oil from aqueous solution. The shell powder and its carbonized material were compared while assessing various factors that influenced oil removal capacity. The structure and sorption mechanism were characterized using scanning electron microscopy and Fourier-transform infrared spectroscopy. The oil removal capacity of the raw material (75.1 mg g
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: 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: Informa UK Limited
Date: 22-11-2014
DOI: 10.4161/EPI.27248
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: Springer Science and Business Media LLC
Date: 25-10-2017
Publisher: MDPI AG
Date: 30-10-2022
Abstract: Sea lettuce (Ulva spp.), with its worldwide distribution and remarkable ability to grow rapidly under various conditions, represents an important natural resource that is still under-exploited. Its biomass can be used for a wide range of applications in the food/feed, pharmaceutical, nutraceutical, biofuel, and bioremediation industries. However, knowledge of the factors affecting Ulva biomass yield and composition is far from complete. Indeed, the respective contributions of the microbiome, natural genetic variation in Ulva species, environmental conditions and importantly, the interactions between these three factors on the Ulva biomass, have been only partially elucidated. Further investigation is important for the implementation of large-scale Ulva aquaculture, which requires stable and controlled biomass composition and yields. In this review, we document Ulva biomass composition, describe the uses of Ulva biomass and we propose different strategies for developing a sustainable and profitable Ulva aquaculture industry.
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: Elsevier BV
Date: 07-2022
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: 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: 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: 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: 27-02-2020
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: 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: 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: 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: Wiley
Date: 2020
DOI: 10.1002/DAD2.12056
Publisher: Elsevier BV
Date: 08-2023
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: 25-01-2017
DOI: 10.1002/MPR.1558
Publisher: Springer Science and Business Media LLC
Date: 07-2019
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: 12-2021
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: Ovid Technologies (Wolters Kluwer Health)
Date: 04-07-2023
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: Oxford University Press (OUP)
Date: 12-2016
DOI: 10.1093/EEP/DVW023
Start Date: 06-2016
End Date: 06-2020
Amount: $453,000.00
Funder: Australian Research Council
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