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Significant evidence demonstrates that aging is associated with variability in cognitive performance, even among individuals who are cognitively normal. In this study, we examined measures from magnetic resonance imaging and cerebrospinal fluid (CSF) to investigate which measures, alone or in combination, were associated with individual differences in episodic memory performance. Using hierarchical linear regressions, we compared the ability of diffusion tensor imaging (DTI) metrics, CSF measures of amyloid and tau, and gray matter volumes to explain variability in memory performance in a cohort of cognitively normal older adults. Measures of DTI microstructure were significantly associated with variance in memory performance, even after accounting for the contribution of the CSF and magnetic resonance imaging gray matter volume measures. Significant associations were found between DTI measures of the hippocampal cingulum and fornix with individual differences in memory. No such relationships were found between memory performance and CSF markers or gray matter volumes. These findings suggest that DTI metrics may be useful in identifying changes associated with aging or age-related diseases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We investigated the effect of baseline Aβ, sex, and APOE on longitudinal tau accumulation in cerebrospinal fluid (CSF) in clinically normal older adults. Two hundred thirty-nine participants (aged 56-89 years, clinical dementia rating = 0) underwent serial CSF collection for Aβ 1-42 , total-tau (t-tau) and phospho-tau 181P (p-tau). We used preprocessed data from fully automated Roche Elecsys immunoassays. A series of linear regressions were used to examine cross-sectional effects of Aβ 1-42 , sex, and APOEε4 on baseline CSF tau and linear mixed models for longitudinal changes in CSF tau. Cross-sectionally, CSF t-tau and p-tau were associated with abnormal Aβ 1-42 and APOEε4 but not with sex. Longitudinally, low baseline CSF Aβ 1-42 levels, but not APOEε4 or sex, predicted faster p-tau accumulation. The relationship between baseline CSF Aβ 1-42 and tau accumulation was strongest in APOEε4 carriers, and particularly female carriers, relative to other groups. The current findings support an association between baseline CSF Aβ 1-42 and changes in CSF tau. Elevated risk in females, apparent only in carriers, reinforces findings of sex-related vulnerability in those with genetic predisposition for Alzheimer's disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Amyloid pathology in cognitively normal older adults has been associated with low memory performance and cognitive complaints, but findings are conflicting. Using a monozygotic twin design, we further explored this relation. We investigated 199 cognitively normal older adults (96 twin pairs) and assessed cognitive performance, cognitive complaints, and amyloid pathology on positron emission tomography and in the cerebrospinal fluid (CSF). Participants were on average 70.5 (SD = 7.6) years and 114 (57%) were female. Amyloid-positron emission tomography abnormality on visual read and lower CSF amyloid-β 1-42/1-40 ratio were associated with lower Rey visuospatial memory performance (respectively, β = -0.39 [SE = 0.17], p = 0.02 and β = 0.15 [SE = 0.07], p = 0.04). Twin analyses showed that CSF amyloid-β 1-42/1-40 ratio in one twin of a pair could predict visuospatial memory performance in the cotwin (r = 0.20 [SE = 0.10], p = 0.04). Monozygotic twin discordance analyses further showed a probable effect of disease staging on face-name associative memory performance. Our results suggest amyloid aggregation to be associated with lower visuospatial and face-name-associated memory performance in cognitively normal older adults, supporting the view that amyloid pathology leads to memory dysfunction in very early stages of the disease., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)