Abstract

Motivation: The influence of Alzheimer’s disease (AD) copathologies on white matter neurite changes in dementia with Lewy bodies (DLB) remains unclear. Goal(s): To delineate the severity of neurite abnormalities and their associations with amyloid and tau PET imaging in DLB. Approach: We compared Neurite Orientation Dispersion and Density Imaging metrics in the DLB spectrum (DLBs, n=45) against controls (n=45), and evaluated their correlations with amyloid-β ([11C]-PiB) and tau ([18F]-Flortaucipir) PET. Results: The DLBs exhibited widespread white matter injury relative to controls. Elevated tau deposition, but not amyloid-β burden, was significantly associated with neurite abnormalities, predominantly involving the temporal and limbic white matter tracts. Impact: These findings demonstrate the impact of AD copathologies on widespread neurite abnormalities in people with DLB, underscoring the importance of further elucidating the mechanisms underlying amyloid-β and tau deposition, and evaluating anti-AD disease-modifying interventions for DLB.