Post mortem MRI of cholinergic white matter pathways across neurodegenerative diseases.

INTRODUCTION: Cholinergic white matter pathway (CWMP) degeneration is central in Alzheimer's disease (AD) and Lewy body disease (LBD). CWMP degeneration can be assessed in vivo using magnetic resonance imaging (MRI) proxies, but neuropathological validation is limited. METHODS: We studied post mortem in situ 3T MRIs of 55 brain donors with standardized neuropathologic assessment (AD, LBD, AD+LBD, other dementias, controls). CWMP integrity was assessed quantitatively using diffusion tensor imaging and visually using the Cholinergic Pathways Hyperintensities Scale (CHIPS) on fluid-attenuated inversion recovery MRI. RESULTS: CWMP diffusivity was strongly associated with CHIPS (p < 0.001), independent of global white matter damage. AD and AD+LBD showed greater CWMP degeneration than LBD, other dementias, and controls (p < 0.05). Multivariate analyses across neuropathological variables identified hippocampal sclerosis and vascular co-pathology as strongest predictors for CWMP degeneration. DISCUSSION: CWMP degeneration is pronounced in AD and mixed AD+LBD pathology and is additionally affected by vascular co-pathology and hippocampal sclerosis. CHIPS may serve as a clinically accessible MRI-based proxy of CWMP integrity.