Abstract
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.