Imaging and genome-supported association of glymphatic system function and multiregional brain characteristics with Parkinson’s disease

This study investigated the genetic and phenotypic associations of the glymphatic system and brain characteristics with Parkinson's disease (PD) and developed an imaging-derived early prediction model. In a case-control analysis of 118 PD patients and 58 matched controls, a lower analysis along the perivascular space (ALPS) index (odds ratio [OR] = 0.049, 95% confidence interval [CI]: 0.013-0.181) and elevated free water content, particularly in the temporal lobe (OR = 5.603, 95% CI: 3.093-10.150), were both associated with PD. Their combination provided the highest predictive accuracy for PD (area under the curve (AUC) = 0.818, 95% CI: 0.750-0.886). Furthermore, Mendelian randomization analysis demonstrated positive causal effects of frontal, occipital, parietal, and temporal lobes on PD risk (OR > 1, p ≤ 0.05). These findings indicate that glymphatic dysfunction and specific brain alterations are associated with PD, and that combining them may improve early prediction strategies.