Search

Introduction: Physical activity (PA) promotes resilience with respect to cognitive decline, although the underlying mechanisms are not well understood. We examined the associations between objectively measured PA and resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) across seven anatomically distributed neural networks., Methods: rs-fcMRI, amyloid beta (Aβ) positron emission tomography (PET), PA (steps/day × 1 week), and longitudinal cognitive (Preclinical Alzheimer's Cognitive Composite) data from 167 cognitively unimpaired adults (ages 63 to 90) were used. We used linear and linear mixed-effects regression models to examine the associations between baseline PA and baseline network connectivity and between PA, network connectivity, and longitudinal cognitive performance., Results: Higher PA was associated selectively with greater connectivity in three networks previously associated with cognitive decline (default, salience, left control). This association with network connectivity accounted for a modest portion of PA's effects on Aβ-related cognitive decline., Discussion: Although other mechanisms are likely present, PA may promote resilience with respect to Aß-related cognitive decline, partly by increasing connectivity in a subset of cognitive networks., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: Cognitive decline follows pathological changes including neurodegeneration on the Alzheimer's disease continuum. However, it is unclear which cognitive domains first become affected by neurodegeneration in amyloid-positive individuals and if sex or apolipoprotein ( APOE ) ε4 status differences affect this relationship., Methods: Data from 1233 cognitively unimpaired, amyloid-positive individuals 65 to 85 years of age were studied to assess the effect of hippocampal volume (HV) on cognition and to evaluate differences due to sex and APOE ε4 status., Results: Lower HV was linked with worse performance on measures of memory (free recall, total recall, logical memory delayed recall, Mini-Mental State Examination [MMSE]), executive functioning (digit symbol substitution, DSS), and the Preclinical Alzheimer's Cognitive Composite (PACC). Among both women and APOE ε4+ individuals, all cognitive measures, except MMSE, were associated with HV. DSS and PACC had the largest effect sizes in differentiating early and intermediate stage neurodegeneration., Discussion: Despite all cognitive measures being associated with HV, cognitive tests show differences in detecting early or late signs of neurodegeneration. Differences exist in association between cognition and neurodegeneration based on sex and APOE ε4 status., Competing Interests: The authors have no conflicts of interest to report except Ellen Grober, PhD, who receives a small royalty for commercial use of the Free and Cued Selective Reminding Test with Immediate Recall. The test is available at no cost for research or clinical activities from the Albert Einstein College of Medicine., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: Engagement in cognitively stimulating work and activities may slow cognitive decline and dementia. We examined the individual and combined associations of four cognitive engagement indices (educational attainment, occupational complexity, social engagement, and cognitively stimulating leisure activities) with objective and subjective cognition., Methods: Middle-aged adults (n = 1864) enrolled in the Healthy Brain Project completed the Cogstate Brief Battery, the Cognitive Function Instrument, and self-report questionnaires of cognitive engagement., Results: Educational attainment and leisure activity engagement were individually associated with memory performance. Participants were classified based on whether they rated highly in zero to four cognitive engagement indices. Compared to participants with no indices, participants with two or more indices performed moderately better on memory., Discussion: Results suggest that greater variety of cognitive engagement across different areas of life is related to better memory in midlife. Possible explanation for this relationship may be increased opportunity for enhancing cognitive reserve, but further investigations are required., Competing Interests: P. Maruff is a full‐time employee of Cogstate Ltd., the company that provides the Cogstate Brief Battery. All other investigators have no relevant disclosures to report., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: Web-based platforms are used increasingly to assess cognitive function in unsupervised settings. The utility of cognitive data arising from unsupervised assessments remains unclear. We examined the acceptability, usability, and validity of unsupervised cognitive testing in middle-aged adults enrolled in the Healthy Brain Project., Methods: A total of 1594 participants completed unsupervised assessments of the Cogstate Brief Battery. Acceptability was defined by the amount of missing data, and usability by examining error of test performance and the time taken to read task instructions and complete tests (learnability)., Results: Overall, we observed high acceptability (98% complete data) and high usability (95% met criteria for low error rates and high learnability). Test validity was confirmed by observation of expected inverse relationships between performance and increasing test difficulty and age., Conclusion: Consideration of test design paired with acceptability and usability criteria can provide valid indices of cognition in the unsupervised settings used to develop registries of individuals at risk for Alzheimer's disease., Competing Interests: S Perin, RF Buckley, MP Pase, N Yassi, and YY Lim report no disclosures. A Schembri and P Maruff are full‐time employees of Cogstate Ltd., (© 2020 the Alzheimer's Association.)

Introduction: While telomere shortening, a marker of cellular aging, may impact the progression of age-related neurodegenerative diseases, its association with cognition is unclear, particularly in the context of Alzheimer's disease (AD) pathology., Methods: Telomere, cognitive, and CSF data from 482 participants in the AD Neuroimaging Initiative (148 cognitively normal, 283 mild cognitive impairment, 51 AD) was leveraged to assess telomere length associations with cognition (measured by memory and executive function) and interactions with CSF amyloid-β, tau, and APOE -ε4 . Secondary analyses assessed brain volume and thickness outcomes., Results: Longer telomeres at baseline were associated with faster executive function decline. Amyloid-β and tau interacted with telomere length on cognition, with longer telomeres related to faster decline among biomarker-positive individuals., Discussion: Telomere associations with cognition shift with AD progression, with longer telomeres related to worse outcomes as pathology increases, highlighting the need for further investigation of telomere length along the AD neuropathological cascade., (© 2019 The Authors.)

Introduction: We aimed to examine the contribution of subjective cognitive decline (SCD) to reduce the number of β-amyloid (Aβ) positron emission tomography scans required for recruiting Aβ+ clinically normal individuals in clinical trials., Methods: Three independent cohorts (890 clinically normal: 72 yrs ± 6.7; Female: 43.4%; SCD+: 24%; apolipoprotein E [ APOE ] ε4+: 28.5%; Aβ+: 32%) were used. SCD was dichotomized from one question. Using logistic regression, we classified Aβ+ using the SCD dichotomy, APOE ε4, sex, and age., Results: SCD increased odds of Aβ+ by 1.58 relative to non-SCD. Female APOE ε4 carriers with SCD exhibited higher odds of Aβ+ (OR = 3.34), whereas male carriers with SCD showed a weaker, opposing effect (OR = 0.37). SCD endorsement reduces the number of Aβ positron emission tomography scans to recruit Aβ+ individuals by 13% and by 9% if APOE ε4 status is known., Conclusion: SCD helps to classify those with high Aβ, even beyond the substantial effect of APOE genotype. Collecting SCD is a feasible method for targeting recruitment for those likely on the AD trajectory., (© 2019 The Authors.)

Introduction: To investigate whether baseline subjective cognitive complaints (SCCs) predict longitudinal decline on neuropsychological testing and whether SCC increases longitudinally, in the setting of high levels of amyloid burden., Methods: Two hundred seventy-nine clinically normal older participants (mean age = 73.7 ± 6.1 years) from the Harvard Aging Brain Study, a cohort of community-dwelling individuals, were followed longitudinally (4.27 ± 1.35 years) with annual subjective memory questionnaires and neuropsychological assessment. 11 C Pittsburgh compound-B positron emission tomography was used to measure cortical amyloid and to classify status (Aβ+/Aβ-) at baseline., Results: Higher baseline SCC predicted more rapid cognitive decline on neuropsychological measures among those with elevated amyloid (t = -2.18, P  < .0001). In addition, longitudinal report of SCC significantly increased over time, with SCC progression most pronounced among Aβ+ individuals (t = 2.24, P  = .0005)., Discussion: SCC may inform risk for future cognitive decline and track progression of self-perceived decline, particularly in those along the AD trajectory, providing potentially important indicators of clinical meaningfulness in AD prevention trials.

Introduction: Alzheimer's disease (AD) patients exhibit temporally graded memory loss with remote memories remaining more intact than recent memories. It is unclear whether this temporal pattern is observable in clinically normal adults with amyloid pathology (i.e. preclinical AD)., Methods: Participants were asked to recall the names of famous figures most prominent recently (famous after 1990) and remotely (famous from 1960-1980) and were provided with a phonemic cue to ensure that memory failure was not purely due to verbal retrieval weaknesses. In addition, participants identified line drawings of objects. Clinically normal older adults (n = 125) were identified as amyloid β positive or negative (Aβ+/-) using Pittsburgh compound B positron emission tomography. The relationship between Aβ+/- and recall of remote and recent famous face-names and objects was examined using repeated measures analyses and general linear models controlling for demographics and media usage., Results: When provided with a phonemic cue, Aβ+ participants recalled the names of fewer recent famous faces compared with Aβ- participants. However, recall of remote famous face-names and objects did not differ by Aβ group., Discussion: Relative sparing of remotely learned information compared with recently learned information is (1) detectable in the preclinical stages of AD and (2) related to amyloid pathology. Both this temporal gradient and assessment of person-centered rather than object-centered semantic information may be particularly meaningful for tracking early memory changes in the AD trajectory.