Abstract
INTRODUCTION
Memory is a strong endophenotype for Alzheimer’s disease (AD) but is typically detectable only after substantial brain change. Genetically linking late-life memory with mid-life brain traits may identify early markers of AD-related cognitive decline.
METHODS
We leveraged GeNetic cOVariance Analyzer (GNOVA) to estimate genetic covariance between genome-wide association studies (GWASs) of memory performance (MEM) and decline (memslopes) and 3935 UK Biobank (UKB) imaging-derived phenotypes (IDPs) across diffusion, structural, and functional modalities, stratifying by cognitive status and apolipoprotein E (APOE) inclusion. Memory GWASs included 24,216 non-Hispanic White older adults (mean = 74.46 years); IDP GWASs included 33,224 European-ancestry mid-life participants (45.1 to 81.8 years, mean = 64.28).
RESULTS
Diffusion and structural IDPs in medial temporal and frontal regions showed the strongest genetic covariance with memory, with additional shared genetic architecture in default mode network functional connectivity.
DISCUSSION
Mid-life brain traits genetically linked to late-life memory map to AD-vulnerable regions, suggesting biologically relevant risk pathways and potential drug targets for cognitive decline.
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This post is Copyright: | July 10, 2026
Neuro-Dementia