Gray matter microstructure from in-vivo diffusion MRI reflects post-mortem neuropathology severity and clinical progression of Alzheimer's disease
Alasmar, Z.; Tremblay, C.; Moqadam, R.; Serrano, G.; Beach, T. G.; Atri, A.; Su, Y.; Zeighami, Y.; Dadar, M.
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INTRODUCTIONDiffusion-weighted imaging derived mean diffusivity (MD) correlates with Alzheimers disease biomarkers, yet its neuropathological correlates remain unclear. METHODSDiffusion-weighted imaging, postmortem neuropathology, and cognitive performance data were obtained from the National Alzheimers Coordinating Center (N=97), Alzheimers 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. RESULTSResults 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. DISCUSSIONIn vivo MD captures distinct AD-related pathologies across brain regions and relates to cognitive trajectories and gene expression.
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