Objective: Clarify how glymphatic clearance impacts cognition in PD and its interaction with established imaging markers.
Background: Impaired glymphatic clearance may contribute to pathological accumulations in Parkinson’s (PD), but how it interacts with other processes causing dementia remains unclear.
Method: We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) as an indirect marker of glymphatic clearance in 98 PD patients (31 PD-poor outcomes: dementia, mild cognitive impairment, frailty or death within 3-year follow-up; 67 PD-good outcomes) and 28 controls. We assessed DTI-ALPS relationship to cognition, white matter (fibre cross-section), cortical thickness, iron accumulation (quantitative susceptibility mapping (QSM)), and plasma markers (phosphorylated tau-181 (p-tau181 and neurofilament light (NFL)) cross-sectionally and longitudinally.
Results: DTI-ALPS was lower in PD-poor outcomes compared to PD-good outcomes and controls (p=0.005) with further longitudinal reductions only in PD-poor outcomes (group*time interaction: β=-0.013, p=0.021). Lower DTI-ALPS was associated with lower fibre cross-section in PD, at baseline and longitudinally but with different spatial distribution from white matter changes relating to PD cognition. There was no correlation between baseline DTI-ALPS and plasma ptau-181 (p=0.642), NFL (p=0.448) or baseline cortical thickness. Lower DTI-ALPS was associated with accelerated cortical thinning within left precentral gyrus and changes in brain iron distribution.
Conclusion: PD patients who develop poor outcomes show impaired glymphatic clearance at baseline that worsened longitudinally. DTI-ALPS correlated with white matter integrity and brain iron accumulation. However, both showed different spatial distribution than that seen in PD dementia; suggesting impaired glymphatic clearance contributes to cognitive decline in a distinct manner.
To cite this abstract in AMA style:
A. Zarkali, G. Thomas, R. Paterson, N. Hannaway, I. Dobreva, A. Heslegrave, E. Veleva, H. Zetterberg, R. Weil. Impaired glymphatic clearance independently contributes to poor outcomes in Parkinson’s disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/impaired-glymphatic-clearance-independently-contributes-to-poor-outcomes-in-parkinsons-disease/. Accessed November 20, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/impaired-glymphatic-clearance-independently-contributes-to-poor-outcomes-in-parkinsons-disease/