Association of diffusion along the perivascular spaces with clinical symptoms and dopaminergic degeneration in Parkinson’s disease

This study aimed to investigate the association between the diffusion tensor image (DTI) analysis along the perivascular space (ALPS) index, striatal dopamine transporter (DAT) availability, and baseline motor and cognitive function in 207 patients with newly diagnosed Parkinson’s disease (PD). All patients underwent brain MRI and 18 F-FP-CIT PET scans, and ALPS index was calculated to assess glymphatic system function. Multiple linear regression analyses demonstrated that ALPS index and DAT availability in the posterior putamen were negatively associated with the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) scores. Mediation analyses showed that ALPS index affected UPDRS-III scores both directly ( β = −10.116, P = 0.002) and indirectly via DAT availability in the posterior putamen ( β = 2.509, P = 0.036). Furthermore, ALPS index and DAT availability in the associative striatum were positively associated with the Mini-Mental State Examination (MMSE) scores. The ALPS index affected MMSE scores both directly ( β = 1.317, P = 0.003) and indirectly via DAT availability in the anterior putamen ( β = −0.169, P = 0.047). The relationship between ALPS index and baseline motor or cognitive function was significant only when striatal dopamine was severely depleted. These findings suggest that glymphatic dysfunction is associated with worse motor and cognitive function in PD and may exert stronger effects when striatal dopamine is severely depleted.