Intense physical activity is associated with cognitive performance in the elderly

Numerous studies have reported positive impacts of physical activity on cognitive function. However, the majority of these studies have utilised physical activity questionnaires or surveys, thus results may have been influenced by reporting biases. Through the objective measurement of routine levels of physical activity via actigraphy, we report a significant association between intensity, but not volume, of physical activity and cognitive functioning. A cohort of 217 participants (aged 60–89 years) wore an actigraphy unit for 7 consecutive days and underwent comprehensive neuropsychological assessment. The cohort was stratified into tertiles based on physical activity intensity. Compared with individuals in the lowest tertile of physical activity intensity, those in the highest tertile scored 9%, 9%, 6% and 21% higher on the digit span, digit symbol, Rey Complex Figure Test (RCFT) copy and Rey Figure Test 30-min recall test, respectively. Statistically, participants in the highest tertile of physical activity intensity performed significantly better on the following cognitive tasks: digit symbol, RCFT copy and verbal fluency test (all P<0.05). The results indicate that intensity rather than quantity of physical activity may be more important in the association between physical activity and cognitive function

Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis.

Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p < 0.001), left and right hippocampal atrophy (p = 0.001, p = 0.023), and ventricular expansion (p < 0.001) were associated with baseline β-amyloid load. Whole brain atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p < 0.02). We provide evidence that rates of atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase

The support person\u27s preferences and perspectives of physical activity programs for older adults with cognitive impairment

Objectives: Physical activity (PA) is beneficial for older adults\u27 cognition. There is limited research investigating perspectives of support persons (SPs) of next-of-kins (NOKs) with cognitive impairment. This exploratory study aimed to investigate perspectives of SPs of older adults with Alzheimer\u27s Dementia (AD) or Mild Cognitive Impairment (MCI). Methods: A telephone survey of 213 SPs of NOKs from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) was undertaken to quantitatively assess SPs\u27 beliefs and knowledge about PA benefits, current PA level of their NOK, and PA program preferences. The contribution of age, gender, diagnosis and mental health symptoms was assessed using multiple logistic regression analyses. Results: Many SPs were aware of PA benefits for memory (64%) and believed it would help their NOK (72%). Older SP age was associated with less awareness of benefits (p = 0.016). SPs caring for male NOKs were more likely to believe that PA would be helpful than those caring for female NOKs (p = 0.049). NOK AD diagnosis (rather than MCI) (p = 0.014), older age (p = 0.005) and female gender (p = 0.043) were associated with lower PA levels. SPs were mixed regarding preference for their NOKs to participate in individual (45%) or group (54%) PA. Many SPs wanted to participate in PA with their NOK (63%). Conclusions: The results highlight that SPs have high levels of awareness of the cognitive benefits of PA, and describe their preferences regarding PA programs. The findings provide new information to inform targeted public health messaging, PA prescribers and providers, and future research directions

Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer’s disease pathology

Background:Heme and iron homeostasis is perturbed in Alzheimer’s disease (AD); therefore, the aim of the studywas to examine the levels and association of heme with iron-binding plasma proteins in cognitively normal (CN),mild cognitive impairment (MCI), and AD individuals from the Australian Imaging, Biomarker and Lifestyle FlagshipStudy of Ageing (AIBL) and Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohorts.Methods:Non-targeted proteomic analysis by high-resolution mass spectrometry was performed to quantify relativeprotein abundances in plasma samples from 144 CN individuals from the AIBL and 94 CN from KARVIAH cohorts and21 MCI and 25 AD from AIBL cohort. ANCOVA models were utilized to assess the differences in plasma proteinsimplicated in heme/iron metabolism, while multiple regression modeling (and partial correlation) was performed toexamine the association between heme and iron proteins, structural neuroimaging, and cognitive measures.Results:Of the plasma proteins implicated in iron and heme metabolism, hemoglobin subunitβ(p= 0.001) was significantlyincreased in AD compared to CN individuals. Multiple regression modeling adjusted for age, sex, APOEε4 genotype, anddisease status in the AIBL cohort revealed lower levels of transferrin but higher levels of hemopexin associated with augmentedbrain amyloid deposition. Meanwhile, transferrin was positively associated with hippocampal volume and MMSE performance,and hemopexin was negatively associated with CDR scores. Partial correlation analysis revealed lack of significant associationsbetween heme/iron proteins in the CN individuals progressing to cognitive impairment.Conclusions:In conclusion, heme and iron dyshomeostasis appears to be a feature of AD. The causal relationship betweenheme/iron metabolism and AD warrants further investigation

A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort

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 individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals 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 individuals. 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 individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial

Plasma apolipoprotein J as a potential biomarker for Alzheimer\u27s disease: Australian Imaging, Biomarkers and Lifestyle study of aging

Introduction: For early detection of Alzheimer\u27s disease (AD), the field needs biomarkers that can be used to detect disease status with high sensitivity and specificity. Apolipoprotein J (ApoJ, also known as clusterin) has long been associated with AD pathogenesis through various pathways. The aim of this study was to investigate the potential of plasma apoJ as a blood biomarker for AD. Methods: Using the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, the present study assayed plasma apoJ levels over baseline and 18 months in 833 individuals. Plasma ApoJ levels were analyzed with respect to clinical classification, age, gender, apolipoprotein E (APOE) ε4 allele status, mini-mental state examination score, plasma amyloid beta (Aβ), neocortical Aβ burden (as measured by Pittsburgh compound B-positron emission tomography), and total adjusted hippocampus volume. Results: ApoJ was significantly higher in both mild cognitive impairment (MCI) and AD groups as compared with healthy controls (HC; P \u3c .0001). ApoJ significantly correlated with both standardized uptake value ratio (SUVR) and hippocampus volume and weakly correlated with the plasma Aβ1-42/Aβ1-40 ratio. Plasma apoJ predicted both MCI and AD from HC with greater than 80% accuracy for AD and greater than 75% accuracy for MCI at both baseline and 18-month time points. Discussion: Mean apoJ levels were significantly higher in both MCI and AD groups. ApoJ was able to differentiate between HC with high SUVR and HC with low SUVR via APOE ε4 allele status, indicating that it may be included in a biomarker panel to identify AD before the onset of clinical symptoms. © 2016 The Authors

Elecsys CSF biomarker immunoassays demonstrate concordance with amyloid-PET imaging

Background: β-amyloid (Aβ) positron emission tomography (PET) imaging is currently the only Food and Drug Administration-approved method to support clinical diagnosis of Alzheimer\u27s disease (AD). However, numerous research studies support the use of cerebrospinal fluid (CSF) biomarkers, as a cost-efficient, quick and equally valid method to define AD pathology. Methods: Using automated Elecsys® assays (Roche Diagnostics) for Aβ (1-42) (Aβ42), Aβ (1-40) (Aβ40), total tau (tTau) and phosphorylated tau (181P) (pTau), we examined CSF samples from 202 participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing cohort, to demonstrate the concordance with pathological AD via PET imaging. Results: Ratios Aβ42/Aβ40, tTau/Aβ42 and pTau/Aβ42 had higher receiver operator characteristic - area under the curve (all 0.94), and greater concordance with Aβ-PET (overall percentage agreement ~ 90%), compared with individual biomarkers. Conclusion: Strong concordance between CSF biomarkers and Aβ-PET status was observed overall, including for cognitively normal participants, further strengthening the association between these markers of AD neuropathological burden for both developmental research studies and for use in clinical trials. © 2020 The Author(s)

A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort

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 individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals 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 individuals. 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 individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial

Higher coffee consumption is associated with slower cognitive decline and less cerebral Aβ-amyloid accumulation over 126 months: Data from the Australian imaging, biomarkers, and lifestyle study

Background: Worldwide, coffee is one of the most popular beverages consumed. Several studies have suggested a protective role of coffee, including reduced risk of Alzheimer’s disease (AD). However, there is limited longitudinal data from cohorts of older adults reporting associations of coffee intake with cognitive decline, in distinct domains, and investigating the neuropathological mechanisms underpinning any such associations. Methods: The aim of the current study was to investigate the relationship between self-reported habitual coffee intake, and cognitive decline assessed using a comprehensive neuropsychological battery in 227 cognitively normal older adults from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study, over 126 months. In a subset of individuals, we also investigated the relationship between habitual coffee intake and cerebral Aβ-amyloid accumulation (n = 60) and brain volumes (n = 51) over 126 months. Results: Higher baseline coffee consumption was associated with slower cognitive decline in executive function, attention, and the AIBL Preclinical AD Cognitive Composite (PACC; shown reliably to measure the first signs of cognitive decline in at-risk cognitively normal populations), and lower likelihood of transitioning to mild cognitive impairment or AD status, over 126 months. Higher baseline coffee consumption was also associated with slower Aβ-amyloid accumulation over 126 months, and lower risk of progressing to “moderate,” “high,” or “very high” Aβ-amyloid burden status over the same time-period. There were no associations between coffee intake and atrophy in total gray matter, white matter, or hippocampal volume. Discussion: Our results further support the hypothesis that coffee intake may be a protective factor against AD, with increased coffee consumption potentially reducing cognitive decline by slowing cerebral Aβ-amyloid accumulation, and thus attenuating the associated neurotoxicity from Aβ-amyloid-mediated oxidative stress and inflammatory processes. Further investigation is required to evaluate whether coffee intake could be incorporated as a modifiable lifestyle factor aimed at delaying AD onset

Amyloid-related memory decline in preclinical Alzheimer\u27s disease in dependent on APOE ε4 and is detectable over 18-months

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 monthes, in 317 cognitively healthy (CN) older adults (47% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SC = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβwas unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer’s disease