Abstract
The apolipoprotein E (APOE) ε4 allele is the most robust genetic risk factor for late-onset Alzheimer's disease (AD). However, the impact of APOE-ε4 status on cognitive trajectories in cognitively normal adults is not as well understood. Questions remain about whether APOE-ε4 status effects on cognitive decline are similar in men and women, and how APOE-ε4 status and age interact to influence decline in different cognitive domains. 1192 cognitively normal adults from the Baltimore Longitudinal Study on Aging (631 men, 561 women, baseline age 50-93) underwent serial assessments using a comprehensive cognitive test battery. Composite cognitive scores were calculated for six cognitive domains including: verbal memory, executive function, attention, language, visual-spatial ability and processing speed. In sex stratified analysis, linear mixed effects models were used to explore age-dependent associations between APOE-ε4 status and longitudinal cognitive trajectories. Where age-dependent relationships were found, the earliest age of divergence in trajectories was estimated. In men, APOE-ε4 status had significant age-dependent effects on longitudinal decline in verbal memory and executive function with APOE-ε4 carriers showing faster rates of decline compared to non-carriers. This divergence in trajectories was detectible from baseline age of 65 and 68, respectively. In women, APOE-ε4 status had a significant age-dependent effect on longitudinal decline in attention with APOE-ε4 carriers showing faster rates of decline compared to non-carriers. This divergence in trajectories was detectible at a baseline age of 66. No significant APOE-ε4 status effects were found for language, visual-spatial ability and processing speed. Results highlight the importance of considering sex and age when assessing APOE-ε4 associated vulnerability to cognitive decline. Understanding these potential interactions is crucial for clinical trials, especially as APOE-ε4 is increasingly used for screening and identifying individuals who may benefit from early interventions to promote successful cognitive aging.
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Schedule a callMore From: Alzheimer's & Dementia: The Journal of the Alzheimer's Association
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