ORCID Profile
0000-0001-8017-8682
Current Organisation
Murdoch University
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Publisher: Wiley
Date: 08-2020
DOI: 10.1111/JNC.15128
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with neurodegenerative processes, that may also aid in identifying potential drug targets. The current study therefore investigated associations between plasma neurofilament light chain (NF‐L), a marker of neurodegeneration, with plasma metabolites that are products of various cellular processes. Plasma NF‐L, measured by ultrasensitive Single molecule array (Simoa) technology (Quanterix) and plasma metabolites, measured by mass‐spectrometry (AbsoluteIDQ® p400HR kit, BIOCRATES), were assessed in the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort comprising 100 cognitively normal older adults. Metabolites belonging to biogenic amine (creatinine, symmetric dimethylarginine, asymmetric dimethylarginine ADMA, kynurenine, trans‐4‐hydroxyproline), amino acid (citrulline, proline, arginine, asparagine, phenylalanine, threonine) and acylcarnitine classes were observed to have positive correlations with plasma NF‐L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Additionally, after stratifying participants based on low/high brain amyloid‐β load (Aβ ±) assessed by positron emission tomography, while creatinine, SDMA and citrulline correlated with NF‐L in both Aβ‐ and Aβ+ groups, ADMA, proline, arginine, asparagine, phenylalanine and acylcarnitine species correlated with NF‐L only in the Aβ+ group after adjusting for confounding variables, suggesting that the association of these metabolites with neurodegeneration may be relevant to AD‐related neuropathology. Metabolites identified to be associated with plasma NF‐L may have the potential to serve as prognostic markers for neurodegenerative diseases, however, further studies are required to validate the current findings in an independent cohort, both cross‐sectionally and longitudinally. image
Publisher: Oxford University Press (OUP)
Date: 21-11-2022
DOI: 10.1093/PM/PNAC180
Abstract: Complex regional pain syndrome (CRPS) is associated with a range of sensory disturbances on the symptomatic side of the body but whether this includes olfaction is uncertain. To clarify this, the aims of this study were to compare ratings of intensity and hedonic appeal of household odorants in CRPS patients and controls, and to determine whether ratings differed between the symptomatic and contralateral sides within the s le of patients. Six odorants (vanilla, fish sauce, vinegar, eucalyptus, almond essence and acetone) were presented sequentially in random order on cottonwool buds held in the midline approximately 1 cm from both nostrils in 37 CRPS patients and 21 pain-free controls. Each odor was rated for intensity and hedonic appeal, and participants reported whether the odor was stronger and/or smelt different on one side than the other. The odorants smelt worse for patients than controls (P & .05 for the symptomatic and contralateral sides) but neither the intensity nor the unpleasantness of the odorants was greater on the symptomatic than contralateral side in the group as-a-whole. These findings suggest that the trigeminal component of olfaction interacts bilaterally with pain-sensitized circuits in the thalamus or higher cortical centers to distort odor perception in patients with CRPS. This aberrant process appears to differ from the mechanism that underlies hemilateral hyperalgesia in other sensory modalities.
Publisher: Wiley
Date: 06-2023
DOI: 10.1002/ALZ.065323
Abstract: Plasma amyloid‐β (Aβ) 1‐42/Aβ1‐40 ratio, phosphorylated‐tau181 (p‐tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NFL) are putative blood‐based biomarkers for Alzheimer’s disease (AD). However, head‐to‐head comparisons of the afore‐mentioned biomarkers across the AD continuum are lacking. Plasma Aβ1‐42, Aβ1‐40, p‐tau181, GFAP and NFL were measured using the Single Molecule Array platform and compared cross‐sectionally in models with and without AD risk factors (age, sex and APOE ε4 status) across the AD continuum in Aβ PET positive confirmed participants (CU Aβ+, n = 39 MCI Aβ+, n = 33 AD Aβ+, n = 46) and Aβ PET negative confirmed participants (CU Aβ‐, n = 81 MCI Aβ‐, n = 26) from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) cohort. Area under the receiver operating characteristic curves (AUCs) for predicting Aβ PET‐/+ status were compared using DeLong test. Associations between plasma biomarker levels at baseline and prospective cognitive decline (CDR‐SOB) and brain Aβ load were also assessed. Lower plasma Aβ1‐42/Aβ1‐40 ratio and higher p‐tau181 and GFAP were observed in preclinical AD (Aβ1‐42/Aβ1‐40 ratio: ∼19% p‐tau181: ∼70% GFAP: ∼52%), prodromal AD (Aβ1‐42/Aβ1‐40 ratio: ∼14% p‐tau181: ∼69% GFAP: ∼45%) and AD (Aβ1‐42/Aβ1‐40 ratio: ∼16% p‐tau181: ∼91% GFAP: ∼85%), and higher plasma NFL was observed in prodromal AD (∼27%) and AD (∼45%) (Figure 1). Based on the AUCs, p‐tau181 performed equivalent to or better than (≥) other biomarkers, in predicting Aβ PET‐/+ status across the AD continuum (p‐tau AUCs for CU Aβ‐ vs CU Aβ+ ∼81%/ MCI Aβ+ ∼86%/ AD ∼92%). A biomarker panel of Aβ1‐42/Aβ1‐40 ratio, p‐tau181 and GFAP performed ≥ the biomarkers alone in predicting Aβ PET‐/+ status across the AD continuum (biomarker panel AUCs for CU Aβ‐ vs CU Aβ+ 90%/ MCI Aβ+ 89%/ AD 96%). Higher p‐tau181 (β = 0.531, p = 3.18E‐08), GFAP (β = 0.530, p = 5.07E‐08) and NFL (β = 0.487, p = 4.76E‐06) were associated with cognitive decline prospectively and lower plasma Aβ1‐42/Aβ1‐40 ratio (β = ‐6.035, p = 1.56E‐04) and higher p‐tau181 (β = 2.823, p = 4.72E‐05) and GFAP (β = 2.075, p = 0.003) were associated with increased Aβ PET load prospectively. These findings suggest that plasma biomarkers are altered across the AD continuum and are associated with cognitive decline and increased brain Aβ load prospectively.
Publisher: Frontiers Media SA
Date: 04-07-2022
DOI: 10.3389/FNEUR.2022.924096
Abstract: Behavioral measures, such as pure-tone audiometry (PTA), are commonly used to determine hearing thresholds, however, PTA does not always provide reliable hearing information in difficult to test in iduals. Therefore, objective measures of hearing sensitivity that require little-to-no active participation from an in idual are needed to facilitate the detection and treatment of hearing loss in difficult to test people. Investigation of the reliability of the auditory steady-state response (ASSR) for measuring hearing thresholds in older adults is limited. This study aimed to investigate if ASSR can be a reliable, objective measure of frequency specific hearing thresholds in older adults. Hearing thresholds were tested at 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz in 50 participants aged between 60 and 85 years old, using automated PTA and ASSR. Hearing thresholds obtained from PTA and ASSR were found to be significantly correlated (p & .001) in a cohort consisting of participants with normal hearing or mild hearing loss. ASSR thresholds were significantly higher as compared to PTA thresholds, but for the majority of cases the difference remained within the clinically acceptable range (15 dB). This study provides some evidence to suggest that ASSR can be a valuable tool for estimating objective frequency-specific hearing thresholds in older adults and indicate that ASSR could be useful in creating hearing treatment plans for older adults who are unable to complete behavioral PTA. Further research on older adults is required to improve the methodological features of ASSR to increase consistency and reliability, as well as minimize some of the limitations associated with this technique.
Publisher: Wiley
Date: 19-01-2023
DOI: 10.1002/ALZ.12950
Abstract: The current study investigated the association between objectively measured physical activity and cognition in older adults over approximately 8 years. We utilized data from 199 cognitively unimpaired in iduals from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, aged ≥60. Actigraphy was used to measure physical activity (intensity, total activity, and energy expenditure) at baseline. Cognition was assessed using a comprehensive cognitive battery every 18‐months. Higher baseline energy expenditure predicted better episodic recall memory and global cognition over the follow‐up period ( p = 0.031 p = 0.047, respectively). Those with higher physical activity intensity and greater total activity also had better global cognition over time (both p = 0.005). Finally, higher total physical activity predicted improved episodic recall memory over time ( p = 0.022). These results suggest that physical activity can preserve cognition and that activity intensity may play an important role in this association. Greater total physical activity predicts preserved episodic memory and global cognition. Moderate intensity physical activity ( .7 metabolic equivalents of task [MET]) predicts preserved global cognition. Expending 373 kilocalories per day may benefit episodic memory and global cognition.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.NEUROBIOLAGING.2018.06.005
Abstract: Cognitive decline is considered an inevitable consequence of aging however, estimates of cognitive aging may be influenced negatively by undetected preclinical Alzheimer's disease (AD). This study aimed to determine the extent to which estimates of cognitive aging were biased by preclinical AD. Cognitively normal older adults (n = 494) with amyloid-β status determined from positron emission tomography neuroimaging underwent serial neuropsychological assessment at 18-month intervals over 72 months. Estimates of the effects of age on verbal memory, working memory, executive function, and processing speed were derived using linear mixed models. The presence of preclinical AD and clinical progression to mild cognitive impairment or dementia during the study were then added to these models as covariates. Initially, age was associated with decline across all 4 cognitive domains. With the effects of elevated amyloid-β and clinical progression controlled, age was no longer associated with decline in verbal or working memory. However, the magnitude of decline was reduced only slightly for executive function and was unchanged for processing speed. Thus, considered together, the results of the study indicate that undetected preclinical AD negatively biases estimates of age-related cognitive decline for verbal and working memory.
Publisher: Springer Science and Business Media LLC
Date: 04-09-2023
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.JAGP.2019.05.008
Abstract: An increasing body of literature suggests a positive, neuroprotective effect for testosterone on cognition in older men. However, randomized clinical trials (RCTs) examining the effects of testosterone supplementation (TS) on cognitive function have been inconclusive. To investigate the potential for TS to prevent cognitive decline in otherwise cognitively healthy older men, by examining the differential effects of TS on cognitively healthy older men in RCTs. Comprehensive search of electronic databases, conference proceedings, and grey literature from 1990 to 2018 was performed to identify RCTs examining the effects of TS on cognition before and after supplementation, in cognitively healthy in iduals. A final s le of 14 eligible RCTs met inclusion criteria. Using pooled random effects expressed as Hedge's g, comparison of placebo versus treatment groups pre- and postsupplementation showed improvements in the treatment group in executive function (g (11) = 0.14, 95% confidence interval [CI]: 0.03-0.26, z = 0.56, p = 0.011). However, it was noted that two studies in our s le did not report a significant increase in mean serum total testosterone (TT) levels in the treatment group after supplementation. Following exclusion of these studies, analysis indicated improvement in the treatment group for the overall cognitive composite (g (11) = 0.18, 95% CI: 0.02-0.33, z = 2.18), psychomotor speed (g (3) = 0.22, 95% CI: 0.01-0.43, z = 2.07) and executive function (g (9) = 0.15, 95% CI: 0.03-0.28, z = 2.35). No significant differences were noted for the global cognition, attention, verbal memory, visuospatial ability or visuospatial memory domains. Overall, our findings support the potential for TS as a preventative measure against cognitive decline, although the effect sizes were small. These findings warrant further observational studies and clinical trials of good methodological quality, to elucidate the effect of TS on cognition.
Publisher: Springer Science and Business Media LLC
Date: 14-01-2017
DOI: 10.1007/S11065-016-9338-9
Abstract: Successfully assisting older adults to maintain or improve cognitive function, particularly when they are dealing with neurodegenerative disorders such as Alzheimer's disease (AD), remains a major challenge. Cognitive training may stimulate neuroplasticity thereby increasing cognitive and brain reserve. Commercial brain training programs are computerized, readily-available, easy-to-administer and adaptive but often lack supportive data and their clinical validation literature has not been previously reviewed. Therefore, in this review, we report the characteristics of commercially available brain training programs, critically assess the number and quality of studies evaluating the empirical evidence of these programs for promoting brain health in healthy older adults, and discuss underlying causal mechanisms. We searched PubMed, Google Scholar and each program's website for relevant studies reporting the effects of computerized cognitive training on cognitively healthy older adults. The evidence for each program was assessed via the number and quality (PEDro score) of studies, including Randomized Control Trials (RCTs). Programs with clinical studies were subsequently classified as possessing Level I, II or III evidence. Out of 18 identified programs, 7 programs were investigated in 26 studies including follow-ups. Two programs were identified as possessing Level I evidence, three programs demonstrated Level II evidence and an additional two programs demonstrated Level III evidence. Overall, studies showed generally high methodological quality (average PEDro score = 7.05). Although caution must be taken regarding any potential bias due to selective reporting, current evidence supports that at least some commercially available computerized brain training products can assist in promoting healthy brain aging.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2021
DOI: 10.1038/S41398-020-01137-1
Abstract: Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood s les, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1–42/Aβ1–40 ratio, a blood-based marker associated with brain Aβ load, in participants (65–90 years) categorised into low (Aβ−, n = 63) and high (Aβ+, n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1–42, and Aβ1–40 were measured using the Single molecule array (Simoa) platform. Plasma GFAP levels were significantly higher ( p 0.00001), and plasma Aβ1–42/Aβ1–40 ratios were significantly lower ( p 0.005), in Aβ+ participants compared to Aβ− participants, adjusted for covariates age, sex, and apolipoprotein E-ε4 carriage. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished Aβ+ from Aβ− (area under the curve, AUC = 0.78), but was outperformed when plasma GFAP was added to the base model (AUC = 0.91) and further improved with plasma Aβ1–42/Aβ1–40 ratio (AUC = 0.92). The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load. Observations from the present study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma Aβ1–42/Aβ1–40 ratios) for cognitively normal older adults at risk of AD.
Publisher: American Psychological Association (APA)
Date: 10-2018
DOI: 10.1037/PAS0000565
Abstract: The ability to read irregularly spelled words is commonly used to estimate premorbid intelligence, as this ability has been thought to be resistant to early effects of neurodegenerative disorders. However, studies evaluating decline of this skill in Alzheimer's disease (AD) have produced conflicting results. Irregular word reading was assessed three times over 36 months in a large (N = 995) s le, including healthy control, AD, and Mild Cognitive Impairment (MCI) groups. At baseline, MCI and AD groups read correctly an average of 3.01 and 7.39 fewer words, respectively, than healthy controls. The MCI group's performance remained stable during the study, but the AD group declined. Importantly, the observed decline was likely an underestimate, as significant numbers of the AD participants (42.6%) could not complete the task at follow-up. Use of alternate (e.g., demographics-based) methods is advised to augment or replace word pronunciation in estimating premorbid intelligence in in iduals with even mild AD. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Publisher: Wiley
Date: 13-11-2014
DOI: 10.1002/GPS.4231
Abstract: The objective was to evaluate in a cognitively normal population the utility of an endophenotype of the depression-cognition link previously shown to be related to cognitive functioning in mild cognitive impairment and Alzheimer's disease. The data of 460 cognitively normal adults aged 32-92 years (M = 63.5, standard deviation = 9.24) from the Western Australian Memory Study with the Cross-national comparisons of the Cambridge Cognitive Examination-revised (CAMCOG-R) scores and 30-item Geriatric Depression Scale (GDS) scores were analyzed to determine the relationship between the five-item depressive endophenotype (DepE) scale drawn from the GDS and level of performance on a measure of cognitive functioning. For the entire s le, there was a nonsignificant trend toward a negative relationship between DepE and CAMCOG-R scores. When analyzed for those 65 years and older, there was a significant negative relationship between the two measures (p = 0.001) with DepE scores significantly increasing the risk for performing more poorly on the CAMCOG-R (odds ratio = 1.53). Analysis of data for those 70 years and older showed that DepE was the only predictor significantly related to poorer CAMCOG-R performance (p = 0.001). For the 70 years and older group, DepE scores significantly increased the risk of poorer CAMCOG-R scores (odds ratio = 2.23). Analysis of the entire s le on the basis of ApoEε4 carrier status revealed that DepE scores were significantly negatively related only to ApoEε4 noncarrier regardless of age. Elevated DepE scores are associated with poor neuropsychological performance among cognitively normal older adults. Use of the DepE may allow for the identification of a subset of older adults where depression is a primary factor in cognitive decline and who may benefit from antidepressant therapies.
Publisher: Bentham Science Publishers Ltd.
Date: 19-10-2016
DOI: 10.2174/1567205013666160603003800
Abstract: This study investigated signs of age related macular degeneration (AMD) in Alzheimer's disease (AD). These age-related diseases primarily affect different parts of the central nervous system but are substantially similar in terms of abnormal extracellular deposits, metabolic and oxidative stress, neuroinflammation and microvascular abnormalities. While AMD is a retinal disease, AD is reported to affect not only the brain but also the retina, with Aβ deposits, neurodegeneration and vascular changes. Large population based studies have provided conflicting results regarding the comorbidity of AD and AMD. This study investigated signs of AMD in a small but well characterized cohort from the Australian Imaging Biomarkers and Lifestyle study of aging (AIBL). The cohort consisted of 22 AD patients (age 70.2 ± 9.0 yrs, 13 male, 9 female) and 101 cognitively normal (CN) participants (age 71.3 ± 6.0 yrs, 40 male, 61 female). In comparison with the CN group, the AD group had a greater proportion of participants with early AMD (p < 0.0001, odds ratio 18.67, 95% CI 4.42 - 78.80). A logistic model for early AMD found a significant association with AD diagnosis (p < 0.0001), after adjusting for confounders (age, smoking, hypertension, high and low density lipoproteins, cataract surgery and APOE ε4 carrier status). The results of this study are consistent with an increased risk of AMD in AD. While the pathophysiology of these diseases are unclear, understanding the shared features between them may provide further knowledge about their pathogenesis and could lead to accelerated development of therapies for both diseases.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2017
DOI: 10.1097/MAO.0000000000001502
Abstract: A significant relationship between hearing loss and cognitive impairment has been previously reported. Overall, improvement in speech perception in quiet and quality of life has been observed after cochlear implantation. However, the impact of hearing loss treatment using cochlear implantation on cognitive functions is yet to be fully elucidated. To investigate the impact of cochlear implantation on cognitive and psychological functions of older adults. Prospective patient-control study. A total of 39 participants took part in the study: 23 cochlear implant (CI) candidates (M = 69.04 ± 12.35 yr) and 16 CI recipients (M = 61.75 ± 15.62 yr). All participants completed an assessment of hearing (pure-tone thresholds and speech perception in quiet), and a computerised, nonverbal test battery of cognitive function assessment, as well as a depression, anxiety, and stress scale. Independent-s le t test scores for the changes between 0 and 12 months revealed that CI recipients performed significantly better on measures of simple reaction time, cognitive flexibility, paired-associate learning, working memory, and strategy use ( p 0.05) compared with implant candidates. Compared with the candidates, recipients also showed significantly lower stress scores ( p 0.05) after 1 year use of a CI. Our results indicate that even in participants with a long duration, severe to profound hearing loss, cochlear implantation has some impact on improving a number of cognitive functions. This finding warrants future longitudinal investigations with a large s le size to examine if the observed cognitive enhancement benefits are sustainable.
Publisher: Cambridge University Press (CUP)
Date: 02-10-2019
DOI: 10.1017/S1041610218001072
Abstract: This study investigated the characteristics of subjective memory complaints (SMCs) and their association with current and future cognitive functions. A cohort of 209 community-dwelling in iduals without dementia aged 47–90 years old was recruited for this 3-year study. Participants underwent neuropsychological and clinical assessments annually. Participants were ided into SMCs and non-memory complainers (NMCs) using a single question at baseline and a memory complaints questionnaire following baseline, to evaluate differential patterns of complaints. In addition, comprehensive assessment of memory complaints was undertaken to evaluate whether severity and consistency of complaints differentially predicted cognitive function. SMC and NMC in iduals were significantly different on various features of SMCs. Greater overall severity (but not consistency) of complaints was significantly associated with current and future cognitive functioning. SMC in iduals present distinctive features of memory complaints as compared to NMCs. Further, the severity of complaints was a significant predictor of future cognition. However, SMC did not significantly predict change over time in this s le. These findings warrant further research into the specific features of SMCs that may portend subsequent neuropathological and cognitive changes when screening in iduals at increased future risk of dementia.
Publisher: Bentham Science Publishers Ltd.
Date: 22-05-2015
DOI: 10.2174/1871527314666150429112112
Abstract: Testosterone replacement therapy (TRT) has been investigated in older men as a preventative treatment against Alzheimer's disease and dementia. However, previous studies have been contradictory. We assessed TRT physiological effects in 44 older men (aged 61 ± 7.7 years) with subjective memory complaints using a double blind, randomized, crossover, placebo-controlled study. Participants were randomized into 2 groups, one group received transdermal testosterone (50 mg) daily for 24 weeks, followed by a 4 week wash-out period, then 24 weeks of placebo the other group received the reverse treatment. Blood evaluation revealed significant increases in total testosterone, free (calculated) testosterone, dihydrotestosterone, and a decrease in luteinizing hormone levels (p<0.001) following TRT. Although there were significant increases in red blood cell counts, hemoglobin and prostate specific antigen levels following TRT, they remained within normal ranges. No significant differences in plasma amyloid beta, estradiol, sex hormone binding globulin, insulin levels, body fat percentage, or body mass index were detected. This is the first carefully controlled study that has investigated the influence of TRT in Indonesian men on blood biomarkers linked to dementia risk. Our study suggests TRT is safe and well-tolerated in this Indonesian cohort, yet longitudinal studies with larger cohorts are needed to assess TRT further, and to establish whether TRT reduces dementia risk.
Publisher: Springer Science and Business Media LLC
Date: 25-10-2017
DOI: 10.1038/S41598-017-14020-9
Abstract: Alzheimer’s Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose in iduals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify in iduals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer’s participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk in iduals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ε4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ε4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of in iduals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.
Publisher: Wiley
Date: 2021
DOI: 10.1002/DAD2.12197
Abstract: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD‐MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD‐MC and could help predict risk for dementia during trial enrollment. We created a dementia risk score by entering standardized gray‐matter volumes from 231 DIAD‐MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD‐MC followed longitudinally. Our risk score separated asymptomatic versus demented DIAD‐MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%–98.2%]) and improved prediction beyond established methods based on familial age of onset. In idualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD‐MC participants for prevention trials.
Publisher: Oxford University Press (OUP)
Date: 12-01-2023
Abstract: In preclinical Alzheimer’s disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy deficit that leads to the accumulation of free radicals, which increases inflammation and damages neurons. When glucose utilization is impaired, ketone bodies offer an alternative energy source. Ketone bodies are synthesized from fats, obtained from either the diet or adipose tissue. Dietary medium-chain fatty acids (MCFAs), which are preferentially metabolized into ketone bodies, have the potential to supply the insulin-resistant brain with energy. This systematic review and meta-analysis aims to review the effect of MCFA supplements on circulating ketone bodies and cognition in in iduals with subjective cognitive decline, mild cognitive impairment, and AD. A comprehensive search of electronic databases was performed on August 12, 2019, to retrieve all publications meeting the inclusion criteria. Alerts were then set to identify any publications after the search date up until January 31, 2021. Data were extracted by 2 authors and assessed by a third. In total, 410 publications were identified, of which 16 (n = 17 studies) met the inclusion criteria. All studies assessing change in levels of blood ketone bodies due to MCFA supplementation (n = 12) reported a significant increase. Cognition outcomes (measured in 13 studies), however, varied, ranging from no improvement (n = 4 studies) to improvement (n = 8 studies) or improvement only in apolipoprotein E allele 4 (APOE ε4) noncarriers (n = 2 studies). One study reported an increase in regional cerebral blood flow in APOE ε4 noncarriers and another reported an increase in energy metabolism in the brain. MCFA supplementation increases circulating ketone body levels, resulting in increased brain energy metabolism. Further research is required to determine whether this MCFA-mediated increase in brain energy metabolism improves cognition. PROSPERO registration number CRD42019146967.
Publisher: Frontiers Media SA
Date: 05-10-2023
Publisher: Frontiers Media SA
Date: 06-10-2021
DOI: 10.3389/FNAGI.2021.729949
Abstract: Alzheimer’s disease (AD) is characterized by the excessive deposition of extracellular amyloid-beta peptide (Aβ) and the build-up of intracellular neurofibrillary tangles containing hyperphosphorylated tau proteins. This leads to neuronal damage, cell death and consequently results in memory and learning impairments leading to dementia. Although the exact cause of AD is not yet clear, numerous studies indicate that oxidative stress, inflammation, and mitochondrial dysfunction significantly contribute to its onset and progression. There is no effective therapeutic approach to stop the progression of AD and its associated symptoms. Thus, early intervention, preferably, pre-clinically when the brain is not significantly affected, is a better option for effective treatment. Natural polyphenols (PP) target multiple AD-related pathways such as protecting the brain from Aβ and tau neurotoxicity, ameliorating oxidative damage and mitochondrial dysfunction. Among natural products, the cereal crop sorghum has some unique features. It is one of the major global grain crops but in the developed world, it is primarily used as feed for farm animals. A broad range of PP, including phenolic acids, flavonoids, and condensed tannins are present in sorghum grain including some classes such as proanthocyanidins that are rarely found in others plants. Pigmented varieties of sorghum have the highest polyphenolic content and antioxidant activity which potentially makes their consumption beneficial for human health through different pathways such as oxidative stress reduction and thus the prevention and treatment of neurodegenerative diseases. This review summarizes the potential of sorghum PP to beneficially affect the neuropathology of AD.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.MAD.2020.111209
Abstract: Alzheimer's disease (AD) is the most common form of dementia. Currently, there is no effective medication for the prevention or treatment of AD. This has led to the search for alternative therapeutic strategies. Coconut oil(CO) has a unique fatty acid composition that is rich in medium chain fatty acids(MCFA), a major portion of which directly reaches the liver via the portal vein, thereby bypassing the lymphatic system. Given that brain glucose hypometabolism is a major early hallmark of AD, detectable well before the onset of symptoms, ketone bodies from MCFA metabolism can potentially serve as an alternative energy source to compensate for lack of glucose utilisation in the brain. Additionally, neuroprotective antioxidant properties of CO have been attributed to its polyphenolic content. This review discusses how the metabolism of CO and MCFA may aid in compensating the glucose hypometabolism observed in the AD brain. Furthermore, we present the current evidence of the neuroprotective properties of CO on cognition, amyloid-β pathogenicity, inflammation and oxidative stress. The current review addresses the influence of CO/MCFA on other chronic disorders that are risk factors for AD, and addresses existing gaps in the literature regarding the use of CO/MCFA as a potential treatment for AD.
Publisher: Bentham Science Publishers Ltd.
Date: 11-05-2016
DOI: 10.2174/1567205013666160315112151
Abstract: Alzheimer's disease (AD) is a degenerative brain disorder and is the most common form of dementia. Minimally invasive approaches are required that combine biomarkers to identify in iduals who are at risk of developing mild cognitive impairment (MCI) and AD, to appropriately target clinical trials for therapeutic discovery as well as lifestyle strategies aimed at prevention. Buccal mucosa cells from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing cohort (n=60) were investigated for cytological markers that could be used to identify both MCI and AD in iduals. Visual scoring of the buccal cytome demonstrated a significantly lower frequency of basal and karyorrhectic cells in the MCI group compared with controls. A high content, automated assay was developed using laser scanning cytometry to simultaneously measure cell types, nuclear DNA content and aneuploidy, neutral lipid content, putative Tau and amyloid-β (Aβ) in buccal cells. DNA content, aneuploidy, neutral lipids and Tau were similar in all groups. However, there was significantly lower Tau protein in both basal and karyolytic buccal cell types compared with differentiated buccal cells. Aβ, as measured by frequency of cells containing Aβ signal, as well as area and integral of Aβ signal, was significantly higher in the AD group compared with the control group. Buccal cell Aβ was correlated with mini-mental state examination (MMSE) scores (r = -0.436, P=0.001) and several blood-based biomarkers. Combining newly identified biomarkers from buccal cells with those already established may offer a potential route for more specific biomarker panels which may substantially increase the likelihood of better predictive markers for earlier diagnosis of AD.
Publisher: Medknow
Date: 2017
Publisher: Frontiers Media SA
Date: 28-03-2022
DOI: 10.3389/FNAGI.2022.771214
Abstract: Previous studies have indicated that physical activity may be beneficial in reducing the risk for Alzheimer's disease (AD), although the underlying mechanisms are not fully understood. The goal of this study was to evaluate the relationship between habitual physical activity levels and brain amyloid deposition and AD-related blood biomarkers (i.e., measured using a novel high-performance mass spectrometry-based assay), in apolipoprotein E (APOE) ε4 carriers and noncarriers. We evaluated 143 cognitively normal older adults, all of whom had brain amyloid deposition assessed using positron emission tomography and had their physical activity levels measured using the International Physical Activity Questionnaire (IPAQ). We observed an inverse correlation between brain amyloidosis and plasma beta-amyloid (Aβ) 1−42 but found no association between brain amyloid and plasma Aβ 1−40 and amyloid precursor protein (APP) 669−711 . Additionally, higher levels of physical activity were associated with lower plasma Aβ 1−40 , Aβ 1−42 , and APP 669−711 levels in APOE ε4 noncarriers. The ratios of Aβ 1−40 /Aβ 1−42 and APP 669−711 /Aβ 1−42 , which have been associated with higher brain amyloidosis in previous studies, differed between APOE ε4 carriers and non-carriers. Taken together, these data indicate a complex relationship between physical activity and brain amyloid deposition and potential blood-based AD biomarkers in cognitively normal older adults. In addition, the role of APOE ε4 is still unclear, and more studies are necessary to bring further clarification.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/828120
Abstract: Objective . We examined the diagnostic value of subjective memory complaints (SMCs) assessed with a single item in a large cross-sectional cohort consisting of families with autosomal dominant Alzheimer’s disease (ADAD) participating in the Dominantly Inherited Alzheimer Network (DIAN). Methods . The baseline s le of 183 mutation carriers (MCs) and 117 noncarriers (NCs) was ided according to Clinical Dementia Rating (CDR) scale into preclinical (CDR 0 MCs: n = 107 NCs: n = 109 ), early symptomatic (CDR 0.5 MCs: n = 48 NCs: n = 8 ), and dementia stage (CDR ≥ 1 MCs: n = 28 NCs: n = 0 ). These groups were sub ided by the presence or absence of SMCs. Results . At CDR 0, SMCs were present in 12.1% of MCs and 9.2% of NCs ( P = 0.6 ) . At CDR 0.5, SMCs were present in 66.7% of MCs and 62.5% of NCs ( P = 1.0 ) . At CDR ≥ 1, SMCs were present in 96.4% of MCs. SMCs in MCs were significantly associated with CDR, logical memory scores, Geriatric Depression Scale, education, and estimated years to onset. Conclusions . The present study shows that SMCs assessed by a single-item scale have no diagnostic value to identify preclinical ADAD in asymptomatic in iduals. These results demonstrate the need of further improvement of SMC measures that should be examined in large clinical trials.
Publisher: Springer Science and Business Media LLC
Date: 20-11-2012
DOI: 10.1038/TP.2012.118
Publisher: Springer Science and Business Media LLC
Date: 21-01-2019
Publisher: Springer Science and Business Media LLC
Date: 29-07-2014
DOI: 10.1038/MP.2014.79
Abstract: The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. In idual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each in idual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) ɛ4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE ɛ4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet.
Publisher: American Medical Association (AMA)
Date: 16-10-2023
Publisher: MDPI AG
Date: 13-03-2021
DOI: 10.3390/IJMS22062931
Abstract: Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3–4 years later (NC = 8 MC = 9). Plasma Aβ1-40 and Aβ1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(Aβ1-40: p = 0.001 Aβ1-42: p = 0.0004) and T2 (Aβ1-40: p = 0.001 Aβ1-42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aβ1-40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma Aβ1-42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma Aβ may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger s le sets are required.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2017
DOI: 10.1038/S41598-017-01327-W
Abstract: The relationship between body-mass index (BMI) and Alzheimer´s disease (AD) has been extensively investigated. However, BMI alterations in preclinical in iduals with autosomal dominant AD (ADAD) have not yet been investigated. We analyzed cross-sectional data from 230 asymptomatic members of families with ADAD participating in the Dominantly Inherited Alzheimer Network (DIAN) study including 120 preclinical mutation carriers (MCs) and 110 asymptomatic non-carriers (NCs). Differences in BMI and their relation with cerebral amyloid load and episodic memory as a function of estimated years to symptom onset (EYO) were analyzed. Preclinical MCs showed significantly lower BMIs compared to NCs, starting 11.2 years before expected symptom onset. However, the BMI curves begun to erge already at 17.8 years before expected symptom onset. Lower BMI in preclinical MCs was significantly associated with less years before estimated symptom onset, higher global Aβ brain burden, and with lower delayed total recall scores in the logical memory test. The study provides cross-sectional evidence that weight loss starts one to two decades before expected symptom onset of ADAD. Our findings point toward a link between the pathophysiology of ADAD and disturbance of weight control mechanisms. Longitudinal follow-up studies are warranted to investigate BMI changes over time.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2018
DOI: 10.1038/S41398-018-0293-5
Abstract: Accumulating research has linked Mediterranean diet (MeDi) adherence with slower cognitive decline and reduced Alzheimer’s disease (AD) risk. However, no study to-date has examined the relationship between MeDi adherence and accumulation of cerebral Aβ-amyloid (Aβ a pathological hallmark of AD) in older adults. Cognitively normal healthy control participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing completed the Cancer Council of Victoria Food Frequency Questionnaire at baseline, which was used to construct a MeDi score for each participant (score range 0–9 higher score indicating higher adherence). Cerebral Aβ load was quantified by Pittsburgh Compound B positron emission tomography at baseline, 18 and 36 months: Only in iduals categorised as “Aβ accumulators”, and thus considered to be on the AD pathway, were included in the analysis ( N = 77). The relationship between MeDi adherence, MeDi components, and change in cerebral Aβ load (baseline to 36 months) was evaluated using Generalised Linear Modelling, accounting for age, gender, education, Apolipoprotein E ε4 allele status, body mass index and total energy intake. Higher MeDi score was associated with less Aβ accumulation in our cohort (β = −0.01 ± 0.004, p = 0.0070). Of the in idual MeDi score components, a high intake of fruit was associated with less accumulation of Aβ (β = −0.04 ± 0.01, p = 0.00036). Our results suggest MeDi adherence is associated with reduced cerebral AD pathology accumulation over time. When our results are considered collectively with previous data linking the MeDi to slower cognitive decline, it is apparent that MeDi adherence warrants further investigation in the quest to delay AD onset.
Publisher: Informa UK Limited
Date: 2012
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.BBR.2019.01.013
Abstract: Higher cardiorespiratory fitness has been associated with better cognitive function in older adults yet, this relationship demonstrates a degree of variability across the older adult population. Thus, it is hypothesised that variation in genetic factors may influence the relationship between fitness and cognitive health. One such genetic factor is the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, which has previously been shown to moderate the relationship between self-reported physical activity and memory performance. In this study we aim to investigate the interaction between BDNF Val66Met polymorphism and objectively-measured cardiorespiratory fitness on performance on tasks assessing verbal and visuospatial memory. Data from ninety-nine cognitively normal men and women aged 60-80 years were used. Fitness was assessed by peak oxygen consumption, and verbal and visuospatial memory were evaluated using well-validated measures. Participants were categorised into: lower-fit Met carriers, higher-fit Met carriers, lower-fit Val/Val, or higher-fit Val/Val. Higher-fit in iduals performed better on a task assessing visuospatial memory, compared with lower-fit in iduals. Furthermore, an interaction between BDNF Val66Met and fitness was observed in terms of visuospatial memory performance on a continuous paired associate learning task whereby lower-fit Met carriers performed 1 standard deviation worse than higher-fit Met carriers. No differences were observed between the higher-fit and lower-fit Val/Val homozygotes. Future intervention studies should evaluate the effect of structured exercise on cognitive health between BDNF Val66Met carriers and Val/Val homozygotes.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.JSAMS.2019.06.013
Abstract: High-intensity exercise is a potential therapeutic tool to postpone or prevent the onset of cognitive decline. However, there is a lack of sufficient evidence regarding the longitudinal effects of structured resistance training on cognitive function in healthy adults. The purpose of this study was to investigate the effect of two ecologically valid, intense 12-week resistance training programs on cognitive function in late middle-aged adults. Single-site parallel randomised controlled trial at the Department of Exercise Science strength and conditioning laboratory. Groups allocated by minimisation randomisation. Forty-five healthy adults (age range=41-69 years) were enrolled and randomised into (A) high-load, long rest resistance training (n=14), or (B) moderate-load, short rest resistance training (n=15) twice per week for 12 weeks, or a non-exercising control (n=16). Follow-up within seven days. Data were collected September 2016-December 2017. Cognitive function assessed using the CogState computerised battery. Assessors were blinded to participant group allocation. Secondary outcomes were maximal muscle strength and body composition. Forty-four participants were analysed in 2018. Delayed verbal memory performance was improved (p=0.02) in resistance training groups (g=0.67-0.79) when compared to the control group, with no differences between training groups. Likewise, increases in maximal muscle strength were observed (p<0.01) in resistance training groups when compared to the control group, with no differences between training groups. No differences in body composition were observed. There were no adverse events or side-effects of the intervention. 12 weeks of intense resistance training improves delayed verbal memory irrespective of training design (i.e., high-load vs. moderate-load). This study is registered at www.anzctr.org.au ACTRN12616000690459.
Publisher: Cold Spring Harbor Laboratory
Date: 06-09-2018
DOI: 10.1101/408955
Abstract: Higher cardiorespiratory fitness has been associated with enhanced cognitive function in older adults yet, this relationship demonstrates a degree of variability. Thus, it is hypothesised that variation in genetic factors may influence the relationship between fitness and cognitive health. In this study we evaluate whether the BDNF Val66Met polymorphism moderates the relationship between cardiorespiratory fitness and verbal and visuospatial memory. Data from ninety-nine cognitively normal men and women aged 60 – 80 years were used. Fitness was assessed by peak oxygen consumption, and verbal and visuospatial memory were evaluated using well-validated measures. Participants were categorised into: lower-fit Met carriers, higher-fit Met carriers, lower-fit Val/Val, or higher-fit Val/Val. A significant interaction was observed between BDNF Val66Met and fitness on visuospatial memory performance whereby lower-fit Met carriers performed 1SD lower than higher-fit Met carriers ( p =0.04). We observed higher levels of fitness mitigated the deleterious effect of BDNF Met allele carriage on visuospatial memory. Future intervention studies should evaluate the effect of structured exercise on cognitive health between BDNF Val66Met carriers and Val/Val homozygotes.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 02-2023
DOI: 10.1111/JGS.18241
Abstract: Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment. We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field‐tested along with the items adapted to written form. We used a combination of in idual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA‐H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors. One hundred and fifty‐nine hearing‐impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA‐H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty‐eight participants were retested between 2–4 weeks after initial testing. After the selection of optimal item set, the final MoCA‐H had an area under the curve of 0.973 (95% CI 0.952–0.994). At a cut‐point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test–retest reliability was 0.92 (95%CI 0.78–0.97). The MoCA‐H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.
Publisher: Springer Science and Business Media LLC
Date: 10-10-2019
DOI: 10.1186/S12974-019-1567-4
Abstract: Blood markers indicative of neurodegeneration (neurofilament light chain NFL), Alzheimer’s disease amyloid pathology (amyloid-β Aβ), and neuroinflammation (kynurenine pathway KP metabolites) have been investigated independently in neurodegenerative diseases. However, the association of these markers of neurodegeneration and AD pathology with neuroinflammation has not been investigated previously. Therefore, the current study examined whether NFL and Aβ correlate with KP metabolites in elderly in iduals to provide insight on the association between blood indicators of neurodegeneration and neuroinflammation. Correlations between KP metabolites, measured using liquid chromatography and gas chromatography coupled with mass spectrometry, and plasma NFL and Aβ concentrations, measured using single molecule array (Simoa) assays, were investigated in elderly in iduals aged 65–90 years, with normal global cognition (Mini-Mental State Examination Score ≥ 26) from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort. A positive correlation between NFL and the kynurenine to tryptophan ratio (K/T) reflecting indoleamine 2,3-dioxygenase activity was observed ( r = .451, p .0001). Positive correlations were also observed between NFL and kynurenine ( r = .364, p .0005), kynurenic acid ( r = .384, p .0001), 3-hydroxykynurenine ( r = .246, p = .014), anthranilic acid ( r = .311, p = .002), and quinolinic acid ( r = .296, p = .003). Further, significant associations were observed between plasma Aβ40 and the K/T ( r = .375, p .0005), kynurenine ( r = .374, p .0005), kynurenic acid ( r = .352, p .0005), anthranilic acid ( r = .381, p .0005), and quinolinic acid ( r = .352, p .0005). Significant associations were also observed between plasma Aβ42 and the K/T ratio ( r = .215, p = .034), kynurenic acid ( r = .214, p = .035), anthranilic acid ( r = .278, p = .006), and quinolinic acid ( r = .224, p = .027) in the cohort. On stratifying participants based on their neocortical Aβ load (NAL) status, NFL correlated with KP metabolites irrespective of NAL status however, associations between plasma Aβ and KP metabolites were only pronounced in in iduals with high NAL while associations in in iduals with low NAL were nearly absent. The current study shows that KP metabolite changes are associated with biomarker evidence of neurodegeneration. Additionally, the association between KP metabolites and plasma Aβ seems to be NAL status dependent. Finally, the current study suggests that an association between neurodegeneration and neuroinflammation manifests in the periphery, suggesting that preventing cytoskeleton cytotoxicity by KP metabolites may have therapeutic potential.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Informa UK Limited
Date: 15-05-2017
DOI: 10.1080/00207454.2016.1182527
Abstract: Purpose/Aim of the study: Poor cardiovascular health, including obesity and altered lipid profiles at mid-life, are linked to increased risk of Alzheimer's disease (AD). The biological mechanisms linking cardiovascular health and cognitive function are unclear though are likely to be multifactorial. This study examined the association between various lipoproteins and cognitive functioning in ageing women. We investigated the relationship between readily available biomarkers (i.e. serum lipoprotein) and cognitive decline in domains associated with increased risk of AD (e.g. episodic verbal memory performance and subjective memory complaint). We report cross-sectional data investigating the relationship between serum total cholesterol, triglycerides, high-density lipoprotein (HDL-C) and low-density lipoprotein with verbal memory and learning ability in 130 women with and without memory complaints (n = 71 and 59, respectively) drawn from a study investigating cognitively healthy Western Australians (average age 62.5 years old). After statistical modelling that controlled for the effects of age, depression and apolipoprotein E genotype, HDL-C was significantly associated with better verbal learning and memory performance, specifically short and long delay-free recalls (F = 3.062 p < .05 and F = 3.2670 p < .05, respectively). Our cross-sectional findings suggest that the positive effect of HDL-C on verbal memory may be present much earlier than previously reported and provide further support for the role of HDL-C in healthy brain ageing. Further exploration of the protective effect of HDL-C on cognitive function in ageing is warranted through follow-up, longitudinal studies.
Publisher: Elsevier BV
Date: 02-2023
DOI: 10.1016/J.BBR.2022.114108
Abstract: Lifestyle factors such as physical activity and optimal sleep are associated with better cognition and lower levels of Alzheimer's disease (AD) biomarkers, including brain beta-amyloid (Aβ) burden. We utilised cross-sectional data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study to determine whether self-reported physical activity (measured via the International Physical Activity Questionnaire) moderates the relationship between self-reported sleep (measured via the Pittsburgh Sleep Quality Index), cognition, and brain Aβ. Participants were 349 community-dwelling cognitively normal older adults (75.3 ± 5.7 years), all of whom underwent comprehensive cognitive assessment. Data from a subset of participants (n = 201) were used for analyses with brain Aβ burden (measured by positron emission tomography) as the outcome. Physical activity moderated the relationship between sleep duration and episodic memory (β = -0.10, SE =0.03, p = .005), and sleep efficiency and episodic memory (β = -0.09, SE =0.04, p = .011), such that greater amounts of physical activity mitigated the impact of suboptimal sleep duration and efficiency on episodic memory. Physical activity also moderated the relationship between sleep duration and brain Aβ (β = -0.13, SE =0.06, p = .031), and overall sleep quality and brain Aβ (β = 0.13, SE =0.06, p = .027). Our findings suggest that physical activity may play an important role in the relationship between sleep and cognitive function, and brain Aβ.
Publisher: American Medical Association (AMA)
Date: 13-06-2017
Publisher: Wiley
Date: 08-2018
DOI: 10.1111/COA.12937
Abstract: Age-related hearing loss (ARHL) is highly prevalent in older adults, and more than two-thirds above age of 70 years suffer from ARHL. Recent studies have established a link between ARHL and cognitive impairment however, most of the studies have used verbally loaded cognitive measures to investigate the association between ARHL and cognition. It is possible that due to hearing impairment, the elderly may experience difficulty in following verbal instructions or completing tasks that heavily rely on hearing during cognitive assessments. This may result in overestimation of cognitive impairment in such in iduals. This baseline cross-sectional study investigated the associations between untreated hearing loss and a number of cognitive functions using a battery of non-verbal cognitive tests. Further, association between hearing loss and psychological status of older adults was examined. Prospective case-controlled study. A total of 119 participants (54 males, M=66.33±10.50 years 65 females M=61.51±11.46 years) were recruited. All participants completed a hearing assessment, a computerised test battery of non-verbal cognitive functions and the depression, anxiety and stress scale. Hierarchical multiple regression analysis results revealed that hearing thresholds significantly associated with the working memory (P<0.05), paired associative learning scores (P<0.05), depression (P<0.001), and anxiety (P<0.001) and stress (P<0.001) scores. Analysis of covariance results revealed that participants with moderately-severe hearing loss performed significantly poorer in paired associative learning and working memory tasks and psychological function tests compared to those with normal hearing. Results of the current study suggest a significant relationship between ARHL and both cognition and psychological status. Our results also have some implications for using non-verbal cognitive tests to evaluate cognitive functions in post-lingually hearing impaired ageing adults, at least for those with more than moderately-severe levels of hearing loss.
Publisher: Bentham Science Publishers Ltd.
Date: 10-03-2016
DOI: 10.2174/1871527315666151110125704
Abstract: Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia. Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer's disease pathology. In a randomized, placebo-controlled, crossover study of men with subjective memory complaint and low testosterone levels, we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning. Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being randomly ided into two groups. The first group (Group A) received 24 weeks of testosterone treatment (T treatment) followed by 4 weeks washout, and then 24 weeks of placebo (P) the second group (Group B) received the same treatments, in reverse order (Placebo, washout, and then T treatment). In group A (TèP), compared to baseline, there was a modest (1 point) but significant improvement in general cognitive functioning as measured by the Mini Mental State Examination (MMSE) following testosterone treatment. This improvement from baseline was sustained following the washout period and crossover to placebo treatment. Similar Mini Mental State Examination (MMSE) scores were observed when comparing testosterone treatment with placebo. In group B (PèT) a significant increase was observed from baseline following testosterone treatment and a trend towards an increase when compared to placebo treatment. Improvements in baseline depression scores (assessed by Geriatric Depression Scale) were observed following testosterone lacebo treatment in both groups, and no difference was observed when comparing testosterone with placebo treatment. Our findings indicate a modest improvement on global cognition with testosterone treatment. Larger clinical trials with a longer follow- up and with the inclusion of blood and brain imaging markers are now needed to conclusively determine the significance of testosterone treatment.
Publisher: Wiley
Date: 07-2016
Publisher: BMJ
Date: 06-2020
DOI: 10.1136/BMJOPEN-2019-033342
Abstract: A number of studies have reported an association between peripheral hearing impairment, central auditory processing and Alzheimer’s disease (AD) and its preclinical stages. Both peripheral hearing impairment and central auditory processing disorders are observed many years prior to the clinical manifestation of AD symptoms, hence, providing a long window of opportunity to investigate potential interventions against neurodegenerative processes. This paper outlines the protocol for a systematic review of studies examining the central auditory processing functions in AD and its preclinical stages, investigated through behavioural (clinical assessments that require active participation) central auditory processing tests. We will use the keywords and Medical Subject Heading terms to search the following electronic databases: MEDLINE, PsychINFO, PubMed, Scopus, EMBASE and CINAHL Plus. Studies including assessments of central auditory function in adults diagnosed with dementia, AD and its preclinical stages that were published before 8 May 2019 will be reviewed. This review protocol will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Data analysis and search results will be reported in the full review. This manuscript has designed the protocols for a systematic review that will identify the behavioural clinical central auditory processing measures that are sensitive to the changes in auditory function in adults with AD and its preclinical stages. Such assessments may subsequently help to design studies to examine the potential impact of hearing and communication rehabilitation of in iduals at risk of AD. Ethical approval is not required as this manuscript only reports the protocols for conducting a systematic review as primary data will only be reviewed and not be collected. The results of this systematic review will be disseminated through publication and in scientific conferences. CRD42017078272.
Publisher: Frontiers Media SA
Date: 21-08-2020
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.NEUROBIOLAGING.2010.09.003
Abstract: A number of genetic risk factors have been identified for Alzheimer's disease (AD) including genes involved in the inflammatory response (interleukin 1A, [IL-1α (-889)], interleukin 1B (IL-1β [+3953]), and tumor necrosis factor (TNF [-308 and -850]). We investigated the prevalence and functional consequences (baseline cognitive performance, plasma cytokine levels) of possession of these putative genetic risk factors within a group of subjective memory complainers (SMC, n = 226) and age and sex matched noncomplainers (NMC, n = 167). We observed no effect of any of the genetic factors investigated on cognitive performance. Further, there was no difference in the frequency of the disease-associated alleles, or cytokine levels between subjective memory complainers and noncomplainer participants. There was no relationship between TNF polymorphisms and TNF levels. There was a significant increase in plasma IL-1β levels in those homozygous for the disease-associated allele (i.e., IL-1β +3953 TT). Follow-up longitudinal assessments on this cohort will provide insight as to how these polymorphisms may affect the risk of cognitive decline over time.
Publisher: Wiley
Date: 10-2023
DOI: 10.1002/GPS.6016
Publisher: Wiley
Date: 21-07-2023
DOI: 10.1002/ALZ.12724
Abstract: Plasma amyloid beta (Aβ)1‐42/Aβ1‐40 ratio, phosphorylated‐tau181 (p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head‐to‐head cross‐sectional and longitudinal comparisons of the aforementioned biomarkers across the AD continuum are lacking. Plasma Aβ1‐42, Aβ1‐40, p‐tau181, GFAP, and NfL were measured utilizing the Single Molecule Array (Simoa) platform and compared cross‐sectionally across the AD continuum, wherein Aβ‐PET (positron emission tomography)–negative cognitively unimpaired (CU Aβ−, n = 81) and mild cognitive impairment (MCI Aβ−, n = 26) participants were compared with Aβ‐PET–positive participants across the AD continuum (CU Aβ+, n = 39 MCI Aβ+, n = 33 AD Aβ+, n = 46) from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) cohort. Longitudinal plasma biomarker changes were also assessed in MCI ( n = 27) and AD ( n = 29) participants compared with CU ( n = 120) participants. In addition, associations between baseline plasma biomarker levels and prospective cognitive decline and Aβ‐PET load were assessed over a 7 to 10‐year duration. Lower plasma Aβ1‐42/Aβ1‐40 ratio and elevated p‐tau181 and GFAP were observed in CU Aβ+, MCI Aβ+, and AD Aβ+, whereas elevated plasma NfL was observed in MCI Aβ+ and AD Aβ+, compared with CU Aβ− and MCI Aβ−. Among the aforementioned plasma biomarkers, for models with and without AD risk factors (age, sex, and apolipoprotein E ( APOE ) ε4 carrier status), p‐tau181 performed equivalent to or better than other biomarkers in predicting a brain Aβ−/+ status across the AD continuum. However, for models with and without the AD risk factors, a biomarker panel of Aβ1‐42/Aβ1‐40, p‐tau181, and GFAP performed equivalent to or better than any of the biomarkers alone in predicting brain Aβ−/+ status across the AD continuum. Longitudinally, plasma Aβ1‐42/Aβ1‐40, p‐tau181, and GFAP were altered in MCI compared with CU, and plasma GFAP and NfL were altered in AD compared with CU. In addition, lower plasma Aβ1‐42/Aβ1‐40 and higher p‐tau181, GFAP, and NfL were associated with prospective cognitive decline and lower plasma Aβ1‐42/Aβ1‐40, and higher p‐tau181 and GFAP were associated with increased Aβ‐PET load prospectively. These findings suggest that plasma biomarkers are altered cross‐sectionally and longitudinally, along the AD continuum, and are prospectively associated with cognitive decline and brain Aβ‐PET load. In addition, although p‐tau181 performed equivalent to or better than other biomarkers in predicting an Aβ−/+ status across the AD continuum, a panel of biomarkers may have superior Aβ−/+ status predictive capability across the AD continuum. Area under the curve (AUC) of p‐tau181 ≥ AUC of Aβ42/40, GFAP, NfL in predicting PET Aβ−/+ status (Aβ−/+). AUC of Aβ42/40+p‐tau181+GFAP panel ≥ AUC of Aβ42/40 ‐tau181/GFAP/NfL for Aβ−/+. Longitudinally, Aβ42/40, p‐tau181, and GFAP were altered in MCI versus CU. Longitudinally, GFAP and NfL were altered in AD versus CU. Aβ42/40, p‐tau181, GFAP, and NfL are associated with prospective cognitive decline. Aβ42/40, p‐tau181, and GFAP are associated with increased PET Aβ load prospectively.
Publisher: Wiley
Date: 15-11-2014
DOI: 10.1016/J.JALZ.2014.06.004
Abstract: Current state-of-the-art diagnostic measures of Alzheimer's disease (AD) are invasive (cerebrospinal fluid analysis), expensive (neuroimaging) and time-consuming (neuropsychological assessment) and thus have limited accessibility as frontline screening and diagnostic tools for AD. Thus, there is an increasing need for additional noninvasive and/or cost-effective tools, allowing identification of subjects in the preclinical or early clinical stages of AD who could be suitable for further cognitive evaluation and dementia diagnostics. Implementation of such tests may facilitate early and potentially more effective therapeutic and preventative strategies for AD. Before applying them in clinical practice, these tools should be examined in ongoing large clinical trials. This review will summarize and highlight the most promising screening tools including neuropsychometric, clinical, blood, and neurophysiological tests.
Publisher: Human Kinetics
Date: 10-2019
Abstract: Objectives : To examine the associations between physical activity duration and intensity, cardiorespiratory fitness, and executive function in older adults. Methods : Data from 99 cognitively normal adults (age = 69.10 ± 5.1 years n = 54 females) were used in the current study. Physical activity (intensity and duration) was measured with the International Physical Activity Questionnaire, and fitness was measured by analysis of maximal aerobic capacity, VO 2 peak. Executive function was measured comprehensively, including measures of Shifting, Updating, Inhibition, Generativity, and Nonverbal Reasoning. Results : Higher levels of cardiorespiratory fitness were associated with better performance on Generativity ( B = .55 95% confidence interval [.15, .97]). No significant associations were found between self-reported physical activity intensity/duration and executive functions. Discussion : To our knowledge, this study is the first to identify an association between fitness and Generativity. Associations between physical activity duration and intensity and executive function requires further study, using objective physical activity measures and longitudinal observations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2018
Publisher: Wiley
Date: 08-09-2022
DOI: 10.1002/ALZ.12447
Abstract: This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t‐tau), phosphorylated tau (p‐tau181 and p‐tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD). Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ−) or presence (Aβ+) of brain amyloidosis. Plasma GFAP, t‐tau, p‐tau181, and p‐tau231 concentrations were higher in Aβ+ CU compared with Aβ− CU cross‐sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ− CU however, no statistically significant differences were observed between the AUCs of GFAP, p‐tau181, and p‐tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t‐tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene ( APOE ) ε4 status with GFAP was observed to have a higher AUC ( %) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p‐tau181 in Aβ+ CU and increased NFL in Aβ− CU, over a 12‐month duration. GFAP, p‐tau181, p‐tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippoc al volume. These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p‐tau for preclinical AD.
Publisher: Wiley
Date: 07-2012
Publisher: Research Square Platform LLC
Date: 07-07-2022
DOI: 10.21203/RS.3.RS-1752559/V2
Abstract: Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer’s disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. We evaluated plasma, serum, and CSF GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease. Plasma GFAP elevations appear a decade before expected symptom onset, after β-amyloid accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished β-amyloid-positive from β-amyloid-negative ADAD participants and showed a stronger relationship with β-amyloid load in asymptomatic than symptomatic ADAD. Higher plasma GFAP was associated with the degree and rate of neurodegeneration and cognitive impairment. Serum GFAP showed similar relationships, but these were less pronounced for CSF GFAP. Our findings support a role for plasma GFAP as a clinical biomarker for β-amyloid-associated cognitive deterioration in AD.
Publisher: Wiley
Date: 07-0007
Publisher: Wiley
Date: 24-08-2022
DOI: 10.1111/JNC.15681
Abstract: Cholesterol levels have been repeatedly linked to Alzheimer's Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) in stable healthy control (HC), healthy controls who will convert to MCI/AD (HC-Conv) and AD patients (AD). Compared to HC we observed an increased cholesterol/ApoA-I ratio in AD and HC-Conv, as well as an increased ApoD/ApoA-I ratio and a decreased ApoA-II/ApoA-I ratio in AD. Higher cholesterol/ApoA-I ratio was also associated with lower cortical grey matter volume and higher ventricular volume, while higher ApoA-II/ApoA-I and ApoJ/ApoA-I ratios were associated with greater cortical grey matter volume (and for ApoA-II also with greater hippoc al volume) and smaller ventricular volume. Additionally, in a clinical status-independent manner, the ApoE/ApoA-I ratio was significantly lower in APOE ε4 carriers and lowest in APOE ε4 homozygous. Together, these data indicate that in AD patients the composition of HDL is altered, which may affect HDL functionality, and such changes are associated with altered regional brain volumetric data.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Springer Science and Business Media LLC
Date: 07-10-2019
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.NEUBIOREV.2016.01.004
Abstract: Traumatic brain injury (TBI) increases the risk of neurodegenerative disorders many years post-injury. However, molecular mechanisms underlying the relationship between TBI and neurodegenerative diseases, such as Alzheimer's disease (AD), remain to be elucidated. Nevertheless, previous studies have demonstrated a link between TBI and increased amyloid-β (Aβ), a protein involved in AD pathogenesis. Here, we review animal studies that measured Aβ levels following TBI. In addition, from a pool of initially identified 1209 published papers, we examined data from 19 eligible animal model studies using a meta-analytic approach. We found an acute increase in cerebral Aβ levels ranging from 24h to one month following TBI (overall log OR=2.97 ± 0.40, p<0.001). These findings may contribute to further understanding the relationship between TBI and future dementia risk. The methodological inconsistencies of the studies discussed in this review suggest the need for improved and more standardised data collection and study design, in order to properly elucidate the role of TBI in the expression and accumulation of Aβ.
Publisher: Wiley
Date: 28-12-2022
DOI: 10.1002/ALZ.12879
Abstract: Glial fibrillary acidic protein (GFAP) is a promising candidate blood‐based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease‐associated changes, its clinical correlates, and biofluid‐type dependency will influence its clinical utility. We evaluated plasma, serum, and cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease. Plasma GFAP elevations appear a decade before expected symptom onset, after amyloid beta (Aβ) accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished Aβ‐positive from Aβ‐negative ADAD participants and showed a stronger relationship with Aβ load in asymptomatic than symptomatic ADAD. Higher plasma GFAP was associated with the degree and rate of neurodegeneration and cognitive impairment. Serum GFAP showed similar relationships, but these were less pronounced for CSF GFAP. Our findings support a role for plasma GFAP as a clinical biomarker of Aβ‐related astrocyte reactivity that is associated with cognitive decline and neurodegeneration. Plasma glial fibrillary acidic protein (GFAP) elevations appear a decade before expected symptom onset in autosomal dominant Alzheimer's disease (ADAD). Plasma GFAP was associated to amyloid positivity in asymptomatic ADAD. Plasma GFAP increased with clinical severity and predicted disease progression. Plasma and serum GFAP carried similar information in ADAD, while cerebrospinal fluid GFAP did not.
Publisher: Oxford University Press (OUP)
Date: 10-2019
Abstract: To prospectively examine 8-year risk of clinical disease progression to mild cognitive impairment (MCI)/dementia in older adults ≥60 with superior episodic memory (SuperAgers) compared to those cognitively normal for their age (CNFA). Additionally, to determine the extent to which SuperAgers were resilient to the negative effects of elevated amyloid-beta (Aβ+) on cognition. Participants were classified as SuperAgers based on episodic memory performance consistent with younger adults aged 30–44 and no impairment on non-memory tests (n = 179), and were matched with CNFA on age, sex, education, and follow-up time (n = 179). Subdistribution hazard models examined risk of clinical progression to MCI/dementia. Linear mixed models assessed the effect of Aβ on cognition over time. Prevalence of Aβ+ and APOE ε4 was equivalent between SuperAgers and CNFA. SuperAgers had 69%–73% reduced risk of clinical progression to MCI/dementia compared to CNFA (HR: 0.27–0.31, 95% CI: 0.11–0.73, p & .001). Aβ+ was associated with cognitive decline in verbal memory and executive function, regardless of SuperAger/CNFA classification. In the absence of Aβ+, equivalent age-related changes in cognition were observed between SuperAgers and CNFA. SuperAgers displayed resilience against clinical progression to MCI/dementia compared to CNFA despite equivalent risk for Alzheimer’s disease (AD) however, SuperAgers had no greater protection from Aβ+ than CNFA. The deleterious effects of Aβ on cognition persist regardless of baseline cognitive ability. Thus, superior cognitive performance does not reflect resistance against the neuropathological processes associated with AD, and the observed resilience for SuperAgers may instead reflect neuropsychological criteria for cognitive impairment.
Publisher: Oxford University Press (OUP)
Date: 05-2016
DOI: 10.5665/SLEEP.5756
Publisher: Wiley
Date: 19-10-2017
Publisher: Bentham Science Publishers Ltd.
Date: 24-02-2015
DOI: 10.2174/1567205012666150204125732
Abstract: This study examines platelet amyloid precursor protein (APP) isoform ratios of 120KDa to 110KDa (APPr) between mutation carriers (MC) carrying a mutation for autosomal dominant Alzheimer's disease (ADAD) and non-carriers (NC). Two previous studies reported no significant difference in APPr between ADAD MC and NC, which may have been due to the small s le size in both studies. The current study examines APPr in MC versus NC in a larger s le. In addition, it investigated whether APPr correlate with neuroimaging data, neuropsychological data and cerebrospinal fluid biomarkers in a cohort subset derived from the Dominantly Inherited Alzheimer Network (DIAN) study. APPr were quantified by western blotting. Fifteen MC (symptomatic and asymptomatic) were compared against twelve NC using univariate general linear model. All participants underwent neuroimaging and neuropsychological testing which were correlated with APPr using Pearson's correlation coefficient (r). APPr were lower in MC compared to NC (p=0.003) while Mini-Mental State Examination (MMSE) scores were not significantly different (p>0.1). Furthermore, APPr inversely correlated with amyloid imaging in the Caudate Nucleus (r=-0.505 p<0.05) and Precuneus (r=-0.510 p<0.05). APPr are lower in ADAD MC compared to NC, and inversely correlated with brain amyloid load prior to significant differences in cognitive health. However, the use of APPr as a biomarker needs to be explored further.
Publisher: Frontiers Media SA
Date: 05-03-2018
Publisher: Springer Science and Business Media LLC
Date: 23-09-2018
DOI: 10.1007/S40279-017-0787-Y
Abstract: A large body of epidemiological and experimental data exploring the relationship between physical activity (PA) and Alzheimer's disease (AD) are now available. Despite observational evidence supporting a role for PA in delaying the onset of AD, randomised controlled trials have reported mixed findings, likely due to the heterogeneity in study cohorts, outcome measures, and the adopted PA intervention. The primary objective of this narrative review is to evaluate the extant evidence on the relationship between PA, cognitive decline and AD in older populations. The interaction between PA and the putative mechanisms underlying AD progression, including genetic factors and amyloid-β levels will be explored. In this context, particular attention will be given to studies assessing PA in the early clinical and preclinical, asymptomatic stages of AD. Based on current evidence, clinical considerations for implementation of exercise-based interventions are discussed, along with limitations of previous research and directions for future studies.
Publisher: Springer Science and Business Media LLC
Date: 11-07-2018
DOI: 10.1038/MP.2017.146
Abstract: Ferritin, an iron storage and regulation protein, has been associated with Alzheimer's disease (AD) however, it has not been investigated in preclinical AD, detected by neocortical amyloid-β load (NAL), before cognitive impairment. Cross-sectional analyses were carried out for plasma and serum ferritin in participants in the Kerr Anglican Retirement Village Initiative in Aging Health cohort. Subjects were aged 65-90 years and were categorized into high and low NAL groups via positron emission tomography using a standard uptake value ratio cutoff=1.35. Ferritin was significantly elevated in participants with high NAL compared with those with low NAL, adjusted for covariates age, sex, apolipoprotein E ɛ4 carriage and levels of C-reactive protein (an inflammation marker). Ferritin was also observed to correlate positively with NAL. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve (AUC)=0.766), but was outperformed when plasma ferritin was added to the base model (AUC=0.810), such that at 75% sensitivity, the specificity increased from 62 to 71% on adding ferritin to the base model, indicating that ferritin is a statistically significant additional predictor of NAL over and above the base model. However, ferritin's contribution alone is relatively minor compared with the base model. The current findings suggest that impaired iron mobilization is an early event in AD pathogenesis. Observations from the present study highlight ferritin's potential to contribute to a blood biomarker panel for preclinical AD.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Bentham Science Publishers Ltd.
Date: 22-08-2017
DOI: 10.2174/1567205014666170309115016
Abstract: This study investigated the retinal arteriolar central reflex (CR, the central reflection observed in photographs of retinal vessels), which may provide information about micro-vascular health in the retina and also the brain, due to the homology between these vascular networks. The study also describes a novel computer based semi-automated technique that accurately quantifies retinal arteriolar CR and vessel width, and calculates the CR to vessel width ratio (CRR) from digital retinal photographs. Digital retinal photographs were collected from participants in the Australian Imaging, Biomarkers and Lifestyle study of ageing (AIBL), including 25 participants diagnosed with Alzheimer's disease (AD) (age 72.4 ± 7.5 yrs, 12 male, 13 female) and 123 elderly participants without dementia (cognitively normals: CN) (age 71.6 ± 5.6 yrs, 55 male, 68 female). Using a sub-cohort of 144 (22 AD, 122 CN) with the novel CRR measures, we identified significantly higher CRR levels in AD participants (mean CRR 0.253 (SD 0.04)) as compared with CN's (mean CRR 0.231 (SD 0.04), p = 0.025). Adjustment for APOE ε4 allele status however, reduced the significance (p = 0.081). CRR was significantly higher in APOE ε4 allele carriers (mean CRR 0.254 (SD 0.03) as compared with non-carriers (mean CRR 0.224 (SD 0.05), p < 0.0001). These data indicate that CRR is strongly linked to APOE ε4 status and exhibits a weaker, independent trend with AD diagnosis. The retina may be useful as a novel model for non-invasive monitoring of the effects of APOE ε4 on the central nervous system, particularly in cerebrovascular disease.
Publisher: Frontiers Media SA
Date: 10-10-2022
Publisher: Springer Science and Business Media LLC
Date: 08-02-2020
DOI: 10.1007/S11065-020-09426-8
Abstract: Some studies have linked bilingualism with a later onset of dementia, Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Not all studies have observed such relationships, however. Differences in study outcomes may be due to methodological limitations and the presence of confounding factors within studies such as immigration status and level of education. We conducted the first systematic review with meta-analysis combining cross-sectional studies to explore if bilingualism might delay symptom onset and diagnosis of dementia, AD, and MCI. Primary outcomes included the age of symptom onset, the age at diagnosis of MCI or dementia, and the risk of developing MCI or dementia. A secondary outcome included the degree of disease severity at dementia diagnosis. There was no difference in the age of MCI diagnosis between monolinguals and bilinguals [mean difference: 3.2 95% confidence intervals (CI): −3.4, 9.7]. Bilinguals vs. monolinguals reported experiencing AD symptoms 4.7 years (95% CI: 3.3, 6.1) later. Bilinguals vs. monolinguals were diagnosed with dementia 3.3 years (95% CI: 1.7, 4.9) later. Here, 95% prediction intervals showed a large dispersion of effect sizes (−1.9 to 8.5). We investigated this dispersion with a subgroup meta-analysis comparing studies that had recruited participants with dementia to studies that had recruited participants with AD on the age of dementia and AD diagnosis between mono- and bilinguals. Results showed that bilinguals vs. monolinguals were 1.9 years (95% CI: −0.9, 4.7) and 4.2 (95% CI: 2.0, 6.4) older than monolinguals at the time of dementia and AD diagnosis, respectively. The mean difference between the two subgroups was not significant. There was no significant risk reduction (odds ratio: 0.89 95% CI: 0.68–1.16) in developing dementia among bilinguals vs. monolinguals. Also, there was no significant difference (Hedges’ g = 0.05 95% CI: −0.13, 0.24) in disease severity at dementia diagnosis between bilinguals and monolinguals, despite bilinguals being significantly older. The majority of studies had adjusted for level of education suggesting that education might not have played a role in the observed delay in dementia among bilinguals vs. monolinguals. Although findings indicated that bilingualism was on average related to a delayed onset of dementia, the magnitude of this relationship varied across different settings. This variation may be due to unexplained heterogeneity and different sources of bias in the included studies. Registration: PROSPERO CRD42015019100.
Publisher: Oxford University Press (OUP)
Date: 24-07-2022
Abstract: The Western Australia Olfactory Memory Test (WAOMT) is a newly developed test designed to meet a need for a comprehensive measure of olfactory episodic memory (OEM) for clinical and research applications. This study aimed to establish the psychometric properties of the WAOMT in a s le of 209 community-dwelling older adults. An independent s le of 27 test-naïve participants were recruited to assess test retest reliability (between 7 and 28 days). Scale psychometric properties were examined using item response theory methods, combined s les (final N = 241). Convergent validity was assessed by comparing performance on the WAOMT with a comprehensive neuropsychological battery of domains (verbal and visual episodic memory, and odor identification), as well as other neuropsychological skills. Based on previous literature, it was predicted that the WAOMT would be positively correlated with conceptually similar cognitive domains. The WAOMT is a psychometrically sound test with adequate reliability properties and demonstrated convergent validity with tests of verbal and episodic memory and smell identification. Patterns of performance highlight learning and memory characteristics unique to OEM (e.g., learning curves, cued and free recall). Clinical and research implications include streamlining future versions of the WAOMT to ease patient and administrative burden, and the potential to reliably detect early neuropathological changes in healthy older adults with nonimpaired OEM abilities.
Publisher: Springer Science and Business Media LLC
Date: 03-2020
Publisher: Springer Science and Business Media LLC
Date: 27-04-2020
Publisher: Elsevier BV
Date: 07-2021
Publisher: Cambridge University Press (CUP)
Date: 15-12-2021
DOI: 10.1017/S1355617720001186
Abstract: Sleep quantity and quality are associated with executive function (EF) in experimental studies, and in in iduals with sleep disorders. With advancing age, sleep quantity and quality decline, as does the ability to perform EF tasks, suggesting that sleep disruption may contribute to age-related EF declines. This cross-sectional cohort study tested the hypothesis that poorer sleep quality (i.e., the frequency and duration of awakenings) and/or quantity may partly account for age-related EF deficits. Community-dwelling older adults ( N = 184) completed actigraphic sleep monitoring then a range of EF tasks. Two EF factors were extracted using exploratory structural equation modeling. Sleep variables did not mediate the relationship between age and EF factors. Post hoc moderated mediation analyses were conducted to test whether cognitive reserve compensates for sleep-related EF deficits, using years of education as a proxy measure of cognitive reserve. We found a significant interaction between cognitive reserve and the number and frequency of awakenings, explaining a small (approximately 3%), but significant amount of variance in EF. Specifically, in in iduals with fewer than 11 years of education, greater sleep disturbance was associated with poorer EF, but sleep did not impact EF in those with more education. There was no association between age and sleep quantity. This study highlights the role of cognitive reserve in the sleep–EF relationship, suggesting in iduals with greater cognitive reserve may be able to counter the impact of disturbed sleep on EF. Therefore, improving sleep may confer some protection against EF deficits in vulnerable older adults.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.NEUROIMAGE.2018.10.044
Abstract: Response inhibition, the ability to withhold a dominant and prepotent response following a change in circumstance or sensory stimuli, declines with advancing age. While non-invasive brain stimulation (NiBS) has shown promise in alleviating some cognitive and motor functions in healthy older in iduals, NiBS research focusing on response inhibition has mostly been conducted on younger adults. These extant studies have primarily focused on modulating the activity of distinct neural regions known to be critical for response inhibition, including the right inferior frontal gyrus (rIFG) and the pre-supplementary motor area (pre-SMA). However, given that changes in structural and functional connectivity have been associated with healthy aging, this review proposes that NiBS protocols aimed at modulating the functional connectivity between the rIFG and pre-SMA may be the most efficacious approach to investigate-and perhaps even alleviate-age-related deficits in inhibitory control.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Springer Science and Business Media LLC
Date: 26-02-2013
DOI: 10.1038/TP.2012.150
Publisher: Wiley
Date: 07-2008
Publisher: Wiley
Date: 13-12-2019
Publisher: Bentham Science Publishers Ltd.
Date: 21-10-2013
DOI: 10.2174/15672050113106660163
Abstract: A screening process that could provide early and accurate diagnosis or prognosis for Alzheimer's disease (AD) would enable earlier intervention, and enable current and future treatments to be more effective. Ocular pathology and changes to vision and ocular function are being investigated for early detection and monitoring of AD. To explore the relationship between pupil flash response (PFR) parameters, AD and brain amyloid plaque burden. Nineteen AD and seventy healthy control (HC) participants were recruited from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. The potential correlations between PFR parameters and 1) AD and 2) brain amyloid plaque burden in the HC group (as a pre-clinical feature of AD), were investigated in this study. Our results demonstrate statistically significant relationships between PFR parameters, neocortical plaque burden and AD. A logistical model combining PFR parameters provided AD-classification performance with sensitivity 84.1%, specificity 78.3% and area under the curve 89.6%. Furthermore, some of the AD specific PFR parameters were also associated with neocortical plaque burden in pre-clinical AD. These PFR changes show potential as an adjunct for noninvasive, cost-effective screening for pre-clinical AD.
Publisher: Wiley
Date: 11-05-2017
Publisher: Springer Science and Business Media LLC
Date: 03-2020
DOI: 10.1007/S11065-020-09435-7
Abstract: The original version of this article unfortunately contained the following mistakes.
Publisher: Bentham Science Publishers Ltd.
Date: 09-2013
Publisher: BMJ
Date: 07-2020
DOI: 10.1136/BMJOPEN-2019-033308
Abstract: Investigating auditory functions in populations at risk of developing Alzheimer’s disease (AD) using auditory neurophysiological measurements can potentially identify a crucial and sensitive diagnostic window of opportunity in preclinical AD. Auditory electrophysiological assessments have gained interest as possible tools for early diagnosis of AD. This paper outlines the protocol that will be used to systematically review the published literature currently available on auditory electrophysiological assessments that have been used to assess the auditory functions of adults over the age of 60 years diagnosed with AD or its preclinical stages. All full-length peer-reviewed publications of original data that use auditory electrophysiological assessments in AD and its preclinical stages (subjective cognitive decline (SCD) and mild cognitive impairment (MCI)) will be considered in this review. The search will be performed on major electronic databases (Ovid MEDLINE, Ovid Embase, PsycINFO, PubMed, Scopus and CINAHL Plus) using keywords alone or in combination with Medical Subject Headings ided into two domains (i) auditory tests and (ii) AD. The database search will be conducted on the 7 th of May 2019. Data analysis will be completed and reported in the full review. A random effects meta-analysis will also be conducted using the Comprehensive Meta-Analysis software, V.3. This review will describe which auditory electrophysiological tests have been found to be useful in assessing the auditory function in cognitively impaired adults (MCI and AD) or adults with serious complaints about their cognition (SCD). This review will also identify and describe which auditory electrophysiological test demonstrates the most sensitivity in differentiating people at different stages of cognitive decline. This systematic review focusses on analysing already available literature. Therefore, there will be no requirement for ethical approval. The systematic review findings will be disseminated through peer-reviewed publication as well as relevant media platforms, for ex le, conferences. PROSPERO CRD42019133553.
Publisher: Frontiers Media SA
Date: 18-02-2015
Publisher: Elsevier BV
Date: 04-2011
Publisher: Springer Science and Business Media LLC
Date: 26-02-2018
DOI: 10.1038/S41398-018-0094-X
Abstract: The glymphatic system is postulated to be a mechanism of brain Aβ-amyloid clearance and to be most effective during sleep. Ablation of the astrocytic end-feet expressed water-channel protein, Aquaporin-4, in mice, results in impairment of this clearance mechanism and increased brain Aβ-amyloid deposition, suggesting that Aquaporin-4 plays a pivotal role in glymphatic function. Currently there is a paucity of literature regarding the impact of AQP4 genetic variation on sleep, brain Aβ-amyloid burden and their relationship to each other in humans. To address this a cross-sectional observational study was undertaken in cognitively normal older adults from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Genetic variants in AQP4 were investigated with respect to self-reported Pittsburgh Sleep Quality Index sleep parameters, positron emission tomography derived brain Aβ-amyloid burden and whether these genetic variants moderated the sleep-Aβ-amyloid burden relationship. One AQP4 variant, rs72878776, was associated with poorer overall sleep quality, while several SNPs moderated the effect of sleep latency (rs491148, rs9951307, rs7135406, rs3875089, rs151246) and duration (rs72878776, rs491148 and rs2339214) on brain Aβ-amyloid burden. This study suggests that AQP4 genetic variation moderates the relationship between sleep and brain Aβ-amyloid burden, which adds weight to the proposed glymphatic system being a potential Aβ-amyloid clearance mechanism and suggests that AQP4 genetic variation may impair this function. Further, AQP4 genetic variation should be considered when interpreting sleep-Aβ relationships.
Publisher: Copernicus GmbH
Date: 18-08-2020
Abstract: Abstract. Results from the fully and biogeochemically coupled simulations in which CO2 increases at a rate of 1 % yr−1 (1pctCO2) from its preindustrial value are analyzed to quantify the magnitude of carbon–concentration and carbon–climate feedback parameters which measure the response of ocean and terrestrial carbon pools to changes in atmospheric CO2 concentration and the resulting change in global climate, respectively. The results are based on 11 comprehensive Earth system models from the most recent (sixth) Coupled Model Intercomparison Project (CMIP6) and compared with eight models from the fifth CMIP (CMIP5). The strength of the carbon–concentration feedback is of comparable magnitudes over land (mean ± standard deviation = 0.97 ± 0.40 PgC ppm−1) and ocean (0.79 ± 0.07 PgC ppm−1), while the carbon–climate feedback over land (−45.1 ± 50.6 PgC ∘C−1) is about 3 times larger than over ocean (−17.2 ± 5.0 PgC ∘C−1). The strength of both feedbacks is an order of magnitude more uncertain over land than over ocean as has been seen in existing studies. These values and their spread from 11 CMIP6 models have not changed significantly compared to CMIP5 models. The absolute values of feedback parameters are lower for land with models that include a representation of nitrogen cycle. The transient climate response to cumulative emissions (TCRE) from the 11 CMIP6 models considered here is 1.77 ± 0.37 ∘C EgC−1 and is similar to that found in CMIP5 models (1.63 ± 0.48 ∘C EgC−1) but with somewhat reduced model spread. The expressions for feedback parameters based on the fully and biogeochemically coupled configurations of the 1pctCO2 simulation are simplified when the small temperature change in the biogeochemically coupled simulation is ignored. Decomposition of the terms of these simplified expressions for the feedback parameters is used to gain insight into the reasons for differing responses among ocean and land carbon cycle models.
Publisher: Cambridge University Press (CUP)
Date: 22-09-2022
DOI: 10.1017/S1355617721001132
Abstract: Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity VO 2peak ) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults. Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention. The intervention was found to increase fitness in the exercise groups, as compared with the control group ( F = 9.88, p = .001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe ( β = 0.29, p = 0.036, r = 0.27), right supplementary motor area ( β = 0.30, p = 0.031, r = 0.29), and both right ( β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus ( β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups. At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in in idual cardiorespiratory fitness was positively associated with frontal GM volume in our s le of older adults. These results provide evidence of in idual variability in exercise-induced fitness on brain structure.
Publisher: Springer Science and Business Media LLC
Date: 25-04-2012
Abstract: Alcadein α (Alc α ) is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-β precursor protein (APP). Successive cleavage of APP by β- and γ-secretases generates the aggregatable amyloid-β peptide (Aβ), while cleavage of APP or Alc α by α- and γ-secretases generates non-aggregatable p3 or p3-Alc α peptides. Aβ and p3-Alc α can be recovered from human cerebrospinal fluid (CSF). We have previously reported alternative processing of APP and Alc α in the CSF of some patients with sporadic mild cognitive impairment (MCI) and AD (SAD). Using the sandwich enzyme-linked immunosorbent assay (ELISA) system that detects total p3-Alc α , we determined levels of total p3-Alc α in CSF from subjects in one of four diagnostic categories (elderly controls, MCI, SAD, or other neurological disease) derived from three independent cohorts. Levels of Aβ40 correlated with levels of total p3-Alc α in all cohorts. We confirm that Aβ40 is the most abundant Aβ species, and we propose a model in which CSF p3-Alc α can serve as a either (1) a nonaggregatable surrogate marker for γ-secretase activity (2) as a marker for clearance of transmembrane domain peptides derived from integral protein catabolism or (3) both. We propose the specification of an MCI/SAD endophenotype characterized by co-elevation of levels of both CSF p3-Alc α and Aβ40, and we propose that subjects in this category might be especially responsive to therapeutics aimed at modulation of γ-secretase function and/or transmembrane domain peptide clearance. These peptides may also be used to monitor the efficacy of therapeutics that target these steps in Aβ metabolis
Publisher: Cambridge University Press (CUP)
Date: 08-2008
DOI: 10.1017/S1041610208006807
Abstract: We note with interest the recently proposed new diagnostic framework published in Lancet Neurology entitled “Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria” by Dubois et al . (2007).
Publisher: Wiley
Date: 12-08-2019
DOI: 10.1002/ANA.25560
Publisher: Wiley
Date: 11-05-2019
Publisher: Elsevier BV
Date: 10-2018
Publisher: Cambridge University Press (CUP)
Date: 22-04-2016
DOI: 10.1017/S0007114516001203
Abstract: Curcumin therapy in animals has produced positive cognitive and behavioural outcomes results of human trials, however, have been inconsistent. In this study, we report the results of a 12-month, randomised, placebo-controlled, double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults. In iduals ( n 96) ingested either placebo or 1500 mg/d Biocurcumax TM for 12 months. A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessments. A significant time×treatment group interaction was observed for the Montreal Cognitive Assessment (repeated-measures analysis time×treatment F =3·85, P ·05). Subsequent analysis revealed that this association was driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group. No differences were observed between the groups for all other clinical and cognitive measures. Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures, ideally in conjunction with biological markers of neurodegeneration.
Publisher: Wiley
Date: 12-08-2019
Publisher: Informa UK Limited
Date: 30-08-2019
DOI: 10.1080/13825585.2018.1513449
Abstract: The high prevalence of sleep disruption among older adults may have implications for cognitive aging, particularly for higher-order aspects of cognition. One domain where sleep disruption may contribute to age-related deficits is prospective memory-the ability to remember to perform deferred actions at the appropriate time in the future. Community-dwelling older adults (55-93 years, N = 133) undertook assessment of sleep using actigraphy and participated in a laboratory-based prospective memory task. After controlling for education, sleep disruption (longer awakenings) was associated with poorer prospective memory. Additionally, longer awakenings mediated the relationship between older age and poorer prospective memory. Other metrics of sleep disruption, including sleep efficiency and wake after sleep onset, were not related to prospective memory, suggesting that examining the features of in idual wake episodes rather than total wake time may help clarify relationships between sleep and cognition. The mediating role of awakening length was partially a function of greater depression and poorer executive function (shifting) but not retrospective memory. This study is among the first to examine the association between objectively measured sleep and prospective memory in older adults. Furthermore, this study is novel in suggesting sleep disruption might contribute to age-related prospective memory deficits perhaps, with implications for cognitive aging more broadly. Our results suggest that there may be opportunities to prevent prospective memory decline by treating sleep problems.
Publisher: Springer Science and Business Media LLC
Date: 22-05-2018
DOI: 10.1038/S41598-018-25968-7
Abstract: The kynurenine pathway (KP) is dysregulated in neuroinflammatory diseases including Alzheimer’s disease (AD), however has not been investigated in preclinical AD characterized by high neocortical amyloid-β load (NAL), prior to cognitive impairment. Serum KP metabolites were measured in the cognitively normal KARVIAH cohort. Participants, aged 65–90 y, were categorised into NAL+ (n = 35) and NAL− (n = 65) using a standard uptake value ratio cut-off = 1.35. Employing linear models adjusting for age and APOE ε4, higher kynurenine and anthranilic acid (AA) in NAL+ versus NAL− participants were observed in females (kynurenine, p = 0.004 AA, p = 0.001) but not males (NALxGender, p = 0.001, 0.038, respectively). To evaluate the predictive potential of kynurenine or/and AA for NAL+ in females, logistic regressions with NAL+/− as outcome were carried out. After age and APOE ε4 adjustment, kynurenine and AA were in idually and jointly significant predictors (p = 0.007, 0.005, 0.0004, respectively). Areas under the receiver operating characteristic curves were 0.794 using age and APOE ε4 as predictors, and 0.844, 0.866 and 0.871 when kynurenine, AA and both were added. Findings from the current study exhibit increased KP activation in NAL+ females and highlight the predictive potential of KP metabolites, AA and kynurenine, for NAL+. Additionally, the current study also provides insight into he influence of gender in AD pathogenesis.
Publisher: Wiley
Date: 11-05-2019
Publisher: Wiley
Date: 11-05-2019
Publisher: Springer Science and Business Media LLC
Date: 06-04-2017
DOI: 10.1038/S41598-017-00751-2
Abstract: Brain and blood fatty acids (FA) are altered in Alzheimer’s disease and cognitively impaired in iduals, however, FA alterations in the preclinical phase, prior to cognitive impairment have not been investigated previously. The current study therefore evaluated erythrocyte FA in cognitively normal elderly participants aged 65–90 years via trans-methylation followed by gas chromatography. The neocortical beta-amyloid load (NAL) measured via positron emission tomography (PET) using ligand 18 F-Florbetaben, was employed to categorise participants as low NAL (standard uptake value ratio SUVR 1.35, N = 65) and high NAL or preclinical AD (SUVR ≥ 1.35, N = 35) wherein, linear models were employed to compare FA compositions between the two groups. Increased arachidonic acid (AA, p 0.05) and decreased docosapentaenoic acid (DPA, p 0.05) were observed in high NAL. To differentiate low from high NAL, the area under the curve (AUC) generated from a ‘base model’ comprising age, gender, APOE ε4 and education (AUC = 0.794) was outperformed by base model + AA:DPA (AUC = 0.836). Our findings suggest that specific alterations in erythrocyte FA composition occur very early in the disease pathogenic trajectory, prior to cognitive impairment. As erythrocyte FA levels are reflective of tissue FA, these alterations may provide insight into the pathogenic mechanism(s) of the disease and may highlight potential early diagnostic markers and therapeutic targets.
Publisher: Cambridge University Press (CUP)
Date: 14-12-2016
DOI: 10.1017/S0007114515004687
Abstract: Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer’s disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (A β ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in A β metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that A β metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence A β metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin’s relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.
Publisher: Wiley
Date: 25-06-2022
DOI: 10.1002/ANA.26429
Abstract: Autosomal‐dominant, Dutch‐type cerebral amyloid angiopathy (D‐CAA) offers a unique opportunity to develop biomarkers for pre‐symptomatic cerebral amyloid angiopathy (CAA). We hypothesized that neuroimaging measures of white matter injury would be present and progressive in D‐CAA prior to hemorrhagic lesions or symptomatic hemorrhage. In a longitudinal cohort of D‐CAA carriers and non‐carriers, we observed ergence of white matter injury measures between D‐CAA carriers and non‐carriers prior to the appearance of cerebral microbleeds and years before the average age of first symptomatic hemorrhage. These results indicate that white matter disruption measures may be valuable cross‐sectional and longitudinal biomarkers of D‐CAA progression. ANN NEUROL 2022 :358–363
Publisher: Wiley
Date: 2022
DOI: 10.1002/TRC2.12348
Abstract: Coronavirus disease 2019 (COVID‐19) has caused .5 million deaths worldwide and affected million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID‐19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID‐19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID‐19 to neurologic illness, both short and long term. This article describes what is known so far in terms of links among COVID‐19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS‐CoV‐2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long‐term neurocognitive sequelae of SARS‐CoV‐2 infection. The following review describes what is known so far in terms of molecular and epidemiological links among COVID‐19, the brain, neurological symptoms, and AD and related dementias (ADRD) The primary objective of this large‐scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long‐term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS‐CoV‐2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS‐CoV‐2 triggers ADRD‐like pathology following the extended olfactory cortical network (EOCN) in older in iduals with specific genetic susceptibility. The proposed harmonization strategies and flexible study designs offer the possibility to include large s les of under‐represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long‐term consequences, and trends in cognitive aging, ADRD, and vascular disease. We provide a framework for current and future studies to be carried out within the Consortium. and offers a “green paper” to the research community with a very broad, global base of support, on tools suitable for low‐ and middle‐income countries aimed to compare and combine future longitudinal data on the topic. The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID‐19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high‐quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.
Publisher: Springer Science and Business Media LLC
Date: 02-2021
DOI: 10.1186/S13195-021-00774-Y
Abstract: Physical inactivity has been consistently linked to increased risk of cognitive decline however, studies examining the impact of exercise interventions on cognition have produced inconsistent findings. Some observational studies suggest exercise intensity may be important for inducing cognitive improvements however, this has yet to be thoroughly examined in older adult cohorts. The objective of the current study was to evaluate the effect of systematically manipulated high-intensity and moderate-intensity exercise interventions on cognition. This multi-arm pilot randomised clinical trial investigated the effects of 6 months of high-intensity exercise and moderate-intensity exercise, compared with an inactive control, on cognition. Outcome measures were assessed at pre- (baseline), post- (6 months), and 12 months post-intervention. Ninety-nine cognitively normal men and women (aged 60–80 years) were enrolled from October 2016 to November 2017. Participants that were allocated to an exercise group (i.e. high-intensity or moderate-intensity) engaged in cycle-based exercise two times per week for 6 months. Cognition was assessed using a comprehensive neuropsychological test battery. Cardiorespiratory fitness was evaluated by a graded exercise test. There was a dose-dependent effect of exercise intensity on cardiorespiratory fitness, whereby the high-intensity group experienced greater increases in fitness than the moderate-intensity and control groups. However, there was no direct effect of exercise on cognition. We did not observe a direct effect of exercise on cognition. Future work in this field should be appropriately designed and powered to examine factors that may contribute to in idual variability in response to intervention. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000643370). Registered on 3 May 2017—retrospectively registered. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372780
Publisher: Springer Science and Business Media LLC
Date: 22-05-2012
DOI: 10.1038/TP.2012.43
Publisher: Springer Science and Business Media LLC
Date: 02-12-2014
DOI: 10.1038/TP.2014.122
Publisher: Informa UK Limited
Date: 31-01-2021
Publisher: Springer Science and Business Media LLC
Date: 31-03-2015
DOI: 10.1038/TP.2015.39
Abstract: In idual biological differences may contribute to the variability of outcomes, including cognitive effects, observed following electroconvulsive treatment (ECT). A narrative review of the research literature on carriage of the apolipoprotein E ɛ4 allele ( APOE-ɛ4 ) and the protein biomarker beta amyloid (Aβ) with ECT cognitive outcome was undertaken. ECT induces repeated brain seizures and there is debate as to whether this causes brain injury and long-term cognitive disruption. The majority of ECT is administered to the elderly (over age 65 years) with drug-resistant depression. Depression in the elderly may be a symptom of the prodromal stage of Alzheimer’s disease (AD). Carriage of the APOE-ɛ4 allele and raised cerebral Aβ are consistently implicated in AD, but inconsistently implicated in brain injury (and related syndromes) recovery rates. A paucity of brain-related recovery, genetic and biomarker research in ECT responses in the elderly was found: three studies have examined the effect of APOE-ɛ4 allele carriage on cognition in the depressed elderly receiving ECT, and two have examined Aβ changes after ECT, with contradictory findings. Cognitive changes in all studies of ECT effects were measured by a variety of psychological tests, making comparisons of such changes between studies problematic. Further, psychological test data-validity measures were not routinely administered, counter to current testing recommendations. The methodological issues of the currently available literature as well as the need for well-designed, hypothesis driven, longitudinal studies are discussed.
No related grants have been discovered for Hamid Reza Sohrabi.