Introduction: Peak width of skeletonized mean diffusivity (PSMD) is a candidate magnetic resonance imaging marker for global white matter integrity. We investigated the value of PSMD in predicting clinical progression in amyloid-positive and amyloid-negative individuals.
Methods: PSMD, cognition, and amyloid status were measured in 254 subjects from the Dementia Disease Initiation (DDI) cohort and 211 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Survival analysis was conducted on 166 DDI subjects and validated in 178 ADNI subjects using Clinical Dementia Rating scale.
Results: High PSMD amyloid-positive individuals had an increased risk of clinical progression relative to those with low PSMD, driven by independent additive effects of amyloid pathology and PSMD. Higher PSMD was predominantly associated with slower processing speed and reduced executive function, but not with memory performance.
Discussion: Combining PSMD with amyloid status may improve the prediction of clinical progression in Alzheimer's disease, particularly in relation to executive and processing speed domains.
Keywords: Alzheimer's disease; PSMD; amyloid beta; clinical progression; survival analysis.
© 2026 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.