Diffusion Tensor Imaging‐Along the Perivascular‐Space Index Is Associated with Disease Progression in Parkinson's Disease

Abstract Background The glymphatic clearance pathway is a waste clearance system that allows for removal of soluble proteins such as amyloid β (Aβ) from the brain. Higher Aβ levels are associated with cognitive dysfunction in Parkinson's disease (PD). Diffusion tensor imaging‐along the perivascular space (DTI‐ALPS) is an imaging measure proposed to indirectly measure glymphatic function. Objectives Evaluate differences in DTI‐ALPS‐index between PD and healthy controls (HC) and characterize relationships between this proposed measure of glymphatic clearance, cognition, and disease severity in PD. Methods PD (n = 32) and HC (n = 23) participants underwent brain imaging to assess DTI‐ALPS. PD participants were classified as PD‐normal cognition (PD‐NC; n = 20) or PD‐mild cognitive impairment (PD‐MCI; n = 12) based on a Level II comprehensive cognitive assessment. A subgroup of PD participants (n = 21) returned for annual assessments for up to 4 years after baseline. Longitudinal outcomes included changes in performance on the comprehensive cognitive assessment and changes in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS). Results PD participants had lower DTI‐ALPS‐index compared to HC. PD participants classified as PD‐MCI had significantly lower DTI‐ALPS‐index compared to PD‐NC. Lower DTI‐ALPS‐index at baseline was associated with longitudinal cognitive decline and worse longitudinal disease severity. Conclusions Glymphatic clearance, as measured with DTI‐ALPS, has potential to serve as a marker of longitudinal disease progression. Interventions targeting glymphatic function should be explored for potential to slow cognitive decline in PD. © 2024 International Parkinson and Movement Disorder Society.