Dataset Information

Impact of sex and APOE ε4 on the association of cognition and hippocampal volume in clinically normal, amyloid positive adults.

ABSTRACT:

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.

SUBMITTER: Petersen KK

PROVIDER: S-EPMC8828988 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Impact of sex and <i>APOE</i> ε4 on the association of cognition and hippocampal volume in clinically normal, amyloid positive adults.

Petersen Kellen K KK Grober Ellen E Lipton Richard B RB Sperling Reisa A RA Buckley Rachel F RF Aisen Paul S PS Ezzati Ali A

Alzheimer's & dementia (Amsterdam, Netherlands) 20220209 1

<h4>Introduction</h4>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 (<i>APOE</i>) ε4 status differences affect this relationship.<h4>Methods</h4>Data from 1233 cognitively unimpaired, amyloid-positive individuals 65 to 85 years of age were studied to assess the effect of hippocampal ...[more]

PMID: 35155730

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Project description:ImportanceTypical cognitive aging may be defined as age-associated changes in cognitive performance in individuals who remain free of dementia. Ideally, the full adult age spectrum should be included to assess brain imaging findings associated with typical aging.ObjectiveTo compare age, sex, and APOE ε4 effects on memory, brain structure (adjusted hippocampal volume [HVa]), and amyloid positron emission tomography (PET) in cognitively normal individuals aged 30 to 95 years old.Design, setting, and participantsCross-sectional observational study (March 2006 to October 2014) at an academic medical center. We studied 1246 cognitively normal individuals, including 1209 participants aged 50 to 95 years old enrolled in a population-based study of cognitive aging and 37 self-selected volunteers aged 30 to 49 years old.Main outcomes and measuresMemory, HVa, and amyloid PET.ResultsOverall, memory worsened from age 30 years through the 90s. The HVa worsened gradually from age 30 years to the mid-60s and more steeply beyond that age. The median amyloid PET was low until age 70 years and increased thereafter. Memory was worse in men than in women overall (P < .001) and more specifically beyond age 40 years. The HVa was lower in men than in women overall (P < .001) and more specifically beyond age 60 years. There was no sex difference in amyloid PET at any age. Within each sex, memory performance and HVa were not different by APOE ε4 status at any age. From age 70 years onward, APOE ε4 carriers had significantly greater median amyloid PET than noncarriers. However, the ages at which 10% of the population were amyloid PET positive were 57 years for APOE ε4 carriers and 64 years for noncarriers.Conclusions and relevanceMale sex is associated with worse memory and HVa among cognitively normal individuals, while APOE ε4 is not. In contrast, APOE ε4 is associated with greater amyloid PET (from age 70 years onward), while sex is not. Worsening memory and HVa occur at earlier ages than abnormal amyloid PET. Therefore, neuropathological processes other than β-amyloidosis must underlie declines in brain structure and memory function in middle age. Our findings are consistent with a model of late-onset Alzheimer disease in which β-amyloidosis arises in later life on a background of preexisting structural and cognitive decline that is associated with aging and not with β-amyloid deposits.