Gu L, Guan X, Gao T, et al. - This study of Parkinson disease (PD) patients indicates that aggravation of white matter (WM) microstructural degeneration occurs due to PD-associated polygenic load and these changes could result in poor cognition with continuous dopamine depletion. This research offers advanced evidence that combined with cumulative polygenic risk scores (PRS) and diffusion tensor imaging (DTI) methods may predict disease progression in PD.

• The Parkinson's Progression Markers Initiative database was used and weighted PRS were calculated using (i) all available 26 PD-risk single nucleotide polymorphisms (SNPs) (PRS1) and (ii) 23 SNPs with minor allele frequency > 0.05 (PRS2).

• By PRS2, and integrated with clinical and DTI data over 3-year follow-up, screening was performed in 60 PD patients and they were allocated to the low-PRS group (n = 30) and high-PRS group (n = 30).

• PRS were linked with younger age at onset in PD patients.

• More extensive WM microstructural degeneration, mainly involving the anterior thalamic radiation (AThR) and inferior fronto-occipital fasciculus, was detected in the high-PRS group vs the low-PRS group.

• WM microstructural alterations in AThR were shown to be correlated with declining cognitive function and increasing dopaminergic deficits in caudate.