MRI-based glymphatic metrics correlate with caudate nucleus dopaminergic deficits and are independent of amyloid-β pathway in Parkinson's disease

Abstract

Background Glymphatic dysfunction is thought to underlie neurodegenerative dementia; however, its interplay with dopaminergic degeneration and concurrent amyloid-β (Aβ) pathology in Parkinson's disease (PD) remains unresolved. This study aimed to evaluate MRI-based glymphatic metrics (the diffusion tensor image analysis along the perivascular space [DTI-ALPS] index and choroid plexus volume [CPV]) and their associations with dopaminergic degeneration, Aβ burden, and cognitive impairment (CI) in PD. Methods 79 PD patients (48 with CI (PD-CI), and 31 cognitive normal (PD-N)) and 28 age-, gender-matched normal controls (NC) were included. Dopaminergic degeneration was measured by dopamine transporter (DAT) availability using 11C-CFT-PET in PD. Additionally, 46 out of 79 PD patients conducted 18F-Florbetapir-PET for quantifying global Aβ burden (Centiloid values) and regional Aβ burden (voxel-wise regression analysis). Results PD-CI showed a significantly reduced DTI-ALPS index (1.31 ± 0.12 vs. 1.40 ± 0.12, p = 0.014; and 1.41 ± 0.12, p = 0.004) and enlarged CPV (1.43 ± 0.31 vs. 1.07 ± 0.18; and 1.14 ± 0.24; p < 0.001 respectively) compared to NC and PD-N. Both the DTI-ALPS index and CPV were significantly correlated with age and caudate DAT availability (CAU_DAT), but not correlated with DAT availability in anterior / posterior putamen, Centiloid values or regional Aβ burden. Further mediation analyses indicated that CAU_DAT mediated the associations between glymphatic metrics and CI after adjustment for covariates, as assessed by the DTI-ALPS index (p = 0.026) and CPV (p = 0.042). Conclusions The caudate dopaminergic degeneration corelates with MRI-based glymphatic metrics and cognitive deterioration in PD.