Abstract
Background Deposition and spreading of misfolded proteins (α-synuclein and tau) have been linked to Parkinson’s cognitive dysfunction. The glymphatic system may play an important role in the clearance of these toxic proteins via cerebrospinal fluid (CSF) flow through perivascular and interstitial spaces. Recent studies discovered that sleep-dependent global brain activity is coupled to CSF flow that may reflect glymphatic function.
Objective To determine if the decoupling of brain activity-CSF flow is linked to Parkinson’s cognitive dysfunction.
Methods Functional and structural MRI data, clinical motor (Unified Parkinson's Disease Rating Scale), and cognitive (Montreal Cognitive Assessment, MoCA) scores were collected from 60 Parkinson’s and 58 control subjects. Parkinson’s patients were subgrouped into those with (MoCA < 26; N = 29) and without (MoCA ≥ 26; N = 31) mild cognitive impairment (MCI).
The coupling strength between the resting-state global blood-oxygen-level-dependent signal (gBOLD) and associated CSF flow was quantified, compared among groups, and associated with clinical and structural measurements.
Results gBOLD-CSF coupling decreased significantly (p < 0.006) in Parkinson’s patients showing MCI, compared to those without MCI and controls. Reduced gBOLD-CSF coupling was associated with decreased MoCA scores that was present in Parkinson’s patients (p = 0.005) but not in controls (p = 0.65). Weaker gBOLD-CSF coupling in Parkinson’s patients also was associated with a thinner right entorhinal cortex (Spearman’s correlation = − 0.36; p = 0.012), an early structural change often seen in Alzheimer’s.
Conclusions The decoupling between global brain activity and associated CSF flow is related to Parkinson’s cognitive impairment.
Competing Interest Statement
The authors have declared no competing interest.
