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Updated: Jul 12, 2026

Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Genetically linked brain imaging markers of memory decline in aging and Alzheimer's disease
Yisu Yang1, Anna Lorenz1, Aditi Sathe1
1Vanderbilt Memory and Alzheimer's Center, Vanderbilt Health, Nashville, Tennessee, USA.
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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