Objective: To investigate glymphatic activity, structural small vessel disease (SVD) markers, and white matter microstructure in Parkinson’s disease (PD) patients, and to explore their associations with clinical and metabolic features.

Background: Glymphatic dysfunction and SVD may contribute to neurodegeneration in PD, yet their relationships with clinical and microstructural brain changes remain incompletely understood.

Method: Seventy-seven PD patients (21 female) were included. Clinical characteristics, MDS-UPDRS-III scores, and levodopa equivalent daily dose (LEDD) were recorded. Glymphatic activity was assessed using the diffusion-based ALPS index (ALPSi). Structural SVD markers included perivascular spaces (PVS) and Fazekas scores. Diffusion tensor imaging (DTI) metrics (fractional anisotropy [FA] and mean diffusivity [MD]) were analyzed across major white-matter tracts. Correlation and multivariable regression analyses were performed, with false discovery rate (FDR) correction for DTI analyses.

Results: Mean age at disease onset was 49.1 ± 10.2 years, disease duration was 9.3 ± 4.1 years, MDS-UPDRS III total score was 54.3 ± 18.8, and LEDD was 1143.5 ± 610.9 mg. Mean right and left ALPS indices were 1.41±0.18 and 1.42±0.23, without hemispheric differences. Right ALPS was independently associated with LEDD (β=0.323, p=0.004). Structural SVD markers were mainly associated with age. PVS counts and Fazekas scores correlated with age-related variables but not with most clinical features after adjustment. DTI analyses demonstrated widespread associations between age and white-matter integrity. Metabolic variables (HbA1c and fasting glucose) were also significantly associated with reduced FA and increased MD across multiple tracts after FDR correction (all p_FDR<0.05). Mean ALPS index showed a positive association with FA in the bilateral anterior thalamic radiations. No significant correlations were observed between ALPS measures and structural SVD markers.

Conclusion: Glymphatic markers, structural small vessel disease burden, and white matter microstructure appear to reflect partially distinct biological processes in PD. While vascular markers were mainly age-related, glymphatic activity correlated with microstructural integrity of the anterior thalamic radiations. These findings highlight complementary pathways of brain vulnerability in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dti-alps-insights-into-glymphatic-dynamics-and-neurovascular-changes-in-parkinsons-disease/