Linking subjective cognitive decline to glymphatic dysfunction in Parkinson's disease

The role of glymphatic system in the subjective cognitive decline (SCD) stage of Parkinson's disease (PD) remains unexplored. This study investigated whether glymphatic dysfunction occurs in PD-SCD and its potential role in mediating the link between sleep disturbance and cognitive impairment.

We recruited 73 PD patients, categorized into three groups: PD with normal cognition (PD-NC, n = 24), PD-SCD (n = 22), and PD with mild cognitive impairment (PD-MCI, n = 27), alongside 27 healthy controls (HC). All participants underwent 3 T MRI to calculate the diffusion tensor image analysis along the perivascular space (ALPS) index and choroid plexus volume (CPV). Clinical assessments included the Montreal Cognitive Assessment (MoCA), PD Sleep Scale (PDSS), and other standardized scales. Mediation analyses examined relationships between sleep quality, glymphatic function, and cognition.

Both PD-SCD and PD-MCI groups showed a significantly decreased ALPS index and increased CPV compared to PD-NC and HC groups (all p < 0.05). The ALPS index positively correlated with PDSS scores (r = 0.407, p = 0.001), MoCA total scores (r = 0.345, p = 0.005), MoCA-memory subscores (r = 0.400, p = 0.001), and MoCA-attention subscores (r = 0.278, p = 0.026). Critically, mediation analysis revealed that the ALPS index fully mediated the relationship between PDSS scores and MoCA-memory performance, but not global cognition or MoCA-attention.

Glymphatic dysfunction is evident during the SCD stage in PD, fully accounting for the statistical association between sleep disturbances and memory performance. This finding highlights glymphatic impairment as a potential neurobiological correlate of cognitive status in PD.