Gray matter microstructure from in-vivo diffusion MRI reflects post-mortem neuropathology severity and clinical progression of Alzheimer's disease.

INTRODUCTION

Diffusion-weighted imaging derived mean diffusivity (MD) correlates with Alzheimer's disease biomarkers, yet its neuropathological correlates remain unclear.

METHODS

Diffusion-weighted imaging, postmortem neuropathology, and cognitive performance data were obtained from the National Alzheimer's Coordinating Center (N=97), Alzheimer's Disease Neuroimaging Initiative (N=21), and Arizona Study of Aging and Neurodegenerative Disorders (N=15). We examined MD associations with neuropathology, cognitive decline, and expression profiles of AD-implicated genes.

RESULTS

Results revealed two latent variables-one linked to amyloid/tau, the other to vascular pathology-explaining 70% and 16% of MD-pathology covariance, respectively. Higher MD correlated with worse cognitive performance, both cross-sectionally and up to 14 years prior to death. MD was regionally associated with Thal phase, neuritic plaque density, Braak stage (temporal/limbic), and infarcts (thalamus), and reflected gene expression patterns related to AD.

DISCUSSION: In vivo MD captures distinct AD-related pathologies across brain regions and relates to cognitive trajectories and gene expression.