Longitudinal genetic and environmental relationships between structural‐ and diffusion‐based Alzheimer’s disease neuroimaging signatures

Composite scores of MRI‐based brain regions associated with Alzheimer’s disease (AD) pathology, commonly termed ‘AD signatures,' are tools developed to identify brain changes specific to mild AD. In recent work from our group, we found that a novel diffusion‐based cortical mean diffusivity (MD) signature among cognitively normal adults in their 50s aided prediction of 12‐year progression to MCI beyond age and polygenic risk for AD. Results held up after accounting for general brain age. In contrast, a cortical thickness/hippocampal volume‐based signature did not improve prediction. Given the importance of genetic influences on brain structure and AD, here we examined the phenotypic and genetic relationships among diffusion and structural AD signatures and brain age, and how those relationships change across midlife and early old age.