Preserved white matter integrity is a promising indicator of cognitive resilience in Parkinson’s disease

Cognitive and motor impairment in Parkinson’s disease (PD) is linked to white matter integrity, yet the prognostic utility of white matter-derived imaging metrics for predicting cognitive and motor decline remains underexplored. Leveraging longitudinal clinical and neuroimaging data from the Parkinson’s Progression Markers Initiative (PPMI) cohort, this study identified microstructural integrity of several specific white matter tracts, including corpus callosum (body, genu, and splenium) and right inferior cerebellar peduncle, as potential indicators for longitudinal cognitive decline in PD patients. Specifically, over a mean follow-up period of 49.13 months, reduced integrity in these tracts was linked to accelerated cognitive decline, while preserved integrity was associated with slower cognitive decline. In contrast, no white matter-based imaging metrics demonstrated significant associations with motor decline after corrections for multiple testing. These findings underscore the critical role of white matter integrity as a potential indicator for tracking longitudinal cognitive deterioration in PD. By pinpointing specific white matter alterations linked to cognitive progression, this study offers valuable insights into the neural substrates of cognitive deficits in PD. Future research should focus on elucidating the molecular mechanisms underlying the relationship between white matter integrity and cognitive function, potentially informing targeted therapeutic strategies to mitigate cognitive impairment and enhance quality of life for PD patients.