Independent Associations of Sleep and Walking with Cognition in Parkinson's Disease: A Perivascular Spaces Analysis

Perivascular spaces (PVSs) support brain waste clearance and are influenced by sleep. In Parkinson's disease (PD), sleep is often disrupted, and can co-occur with gait dysfunction. This study investigated how sleep disruption, walking difficulties, and cognition relate in PD, considering PVS as a mediator. Our cohort included 348 participants -healthy controls (HC, n=59), prodromal (n=117), and PD patients (n=172)- in the Parkinson's Progression Markers Initiative (PPMI) study. Insomnia and walking issues were assessed by questionnaire, cognition was measured with the Symbol Digit Modalities (SDM) test, and PVS volume fraction in white matter (WM-PVS) and basal ganglia (BG-PVS) was quantified. PVS did not mediate the relationship between sleep or motor problems, on cognition. Walking difficulties were directly linked to poorer cognition, and insomnia to walking deficits. BG-PVS was negatively associated with cognition. PVS burden predicted cognitive function after five years, but not disease progression as indexed by cerebro-spinal fluid (CSF) biomarkers. These findings suggest walking deficits directly relate with cognition in PD, but the relationship is not mediated by PVS.