Abstract
IntroductionCognitive 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.MethodsData 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.ResultsLower 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.DiscussionDespite 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
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