Objective: To determine whether the Peak width of Skeletonised Mean Diffusivity (PSMD), an automated diffusion MRI–derived marker of white matter microstructural integrity, differs between individuals with Parkinson’s disease (PD) and controls, and whether PSMD is associated with global cognitive performance.

Background: White matter pathology is increasingly recognised as an important contributor to cognitive impairment in PD. PSMD quantifies variability in white matter diffusivity and has emerged as a sensitive imaging biomarker of microstructural damage. Because PSMD can be derived using fully automated pipelines, it has potential utility for large-scale studies and future clinical applications. However, its relevance to cognitive impairment in PD remains unclear.

Method: Cross-sectional diffusion MRI data were analysed from 49 control and 194 PD participants recruited at the New Zealand Brain Research Institute, Christchurch. Participants completed neuropsychological testing and MRI scanning (single shell diffusion-weighted with 28 diffusion-encoded directions (b=1000 s/mm²) and 4 volumes without diffusion-weighting), and were stratified by diagnostic category (cognitively healthy controls (n=49), cognitively normal PD (n=86), PD with mild cognitive impairment (n=78), and PD dementia (n=30)). PSMD values were derived using a fully automated containerised processing pipeline from the diffusion-weighted acquisition. Group differences in PSMD were assessed using linear models, accounting for age, sex, and relative motion during the acquisition. Associations between PSMD and global cognitive performance were examined using linear regression, adjusting for age, sex, and motion.

Results: PSMD was significantly higher in individuals with PD compared with controls after adjusting for covariates (β = 3.52 × 10⁻⁵, p < 0.001). Higher PSMD was also significantly associated with worse global cognitive performance (β = −0.30 per SD increase in PSMD, p < 0.001). Within individuals with PD, higher PSMD remained significantly associated with worse global cognitive performance after adjusting for covariates (β = −0.16 per SD increase in PSMD, p = 0.022).

Conclusion: PSMD was elevated in PD and significantly associated with global cognitive performance. These findings support PSMD as a promising imaging biomarker for characterising white matter pathology and cognitive impairment in PD. Ongoing work is investigating PSMD over time.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/peak-mean-skeletal-diffusivity-as-a-marker-of-cognitive-impairment-in-parkinsons-disease/