Perivascular space in Parkinson's disease: Association with CSF amyloid/tau and cognitive decline.

OBJECTIVE: Whether perivascular space (PVS) visible on magnetic resonance imaging (MRI) represents glymphatic dysfunction and whether this imaging marker is pathologic in Parkinson's disease (PD) have been controversial. The objective was to determine whether PVS visible on MRI is independently associated with cognitive decline in patients with PD, and to test whether pathologic proteins in the CSF (such as Aß42) mediate the pathologic role of PVS. METHODS: A total of 341 patients with Parkinson's disease from Parkinson's Progression Marker Initiative (PPMI) cohort was included in the present study. PVS in the basal ganglia (BG-PVS) and centrum semiovale were evaluated with a semiquantitative scale. Changes in the Montreal Cognitive Assessment (MoCA) score and the absolute MoCA score at the 3-year assessment were considered the main cognitive outcome. A multivariable linear regression model was used to test the association between PVS and cognitive decline. A mixed linear model and path analysis were used to test the interaction among PVS, CSF biomarkers and cognitive decline. RESULTS: BG-PVS was associated with cognitive decline in patients with PD at the 3-year follow-up independent of age, baseline cognition, motor and nonmotor function, presynaptic dopaminergic deficiency, and CSF biomarkers. The interaction between BG-PVS and Aß42/tTau, Aß42/pTau, and Aß42 levels was significantly predictive of 3-year cognitive decline. Path analysis confirmed that CSF Aß42/tTau levels partially mediated the pathologic effect of BG-PVS on cognitive outcome in PD. CONCLUSIONS: BG-PVS is independently associated with cognitive decline in PD, and this association may be partially mediated by toxic CSF proteins.