ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026
Evidence of APOE4-related brain vulnerabilities in verbal memory systems in midlife women.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionWomen carrying the apolipoprotein E4 (APOE4) allele have a greater risk of Alzheimer's disease (AD) from ages 65-75 years compared to men, yet the effects of APOE4 on cognitive and neuroimaging outcomes among midlife women remain poorly understood. We investigated APOE4-related differences in memory-based functional neuroimaging outcomes in cognitively normal, midlife postmenopausal women.
methodsWe measured blood-oxygen-level-dependent activation and hippocampal functional connectivity during a functional magnetic resonance imaging verbal encoding task. Linear regression models tested APOE4 differences (carriers vs. non-carriers) and associations of neuroimaging indices with verbal memory measures and plasma AD biomarkers, adjusting for age, race, and education.
resultsAmong 145 women from MsBrain, APOE4 carriers and non-carriers did not differ in verbal memory performance or AD biomarker levels. During verbal encoding, APOE4 carriers had significantly decreased activation and hippocampal functional connectivity in several regions compared to non-carriers. DISCUSSION: APOE4-related functional brain differences are present by midlife in postmenopausal women.
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