Objective: To evaluate whether altered cerebrovascular reactivity contributes to reduced glymphatic clearance in Parkinson’s disease (PD).

Background: Cerebrovascular activity is a major factor driving cerebrospinal fluid (CSF) flow dynamics [1,2], which are implicated in glymphatic clearance of interstitial solutes in the brain. We recently demonstrated that patients with PD exhibit reduced and delayed cerebrovascular reactivity [3]. The current study is a preliminary analysis to evaluate to what extent altered cerebrovascular reactivity influences CSF influx in response to a vasodilatory challenge.    

Method: 18 PD and 21 age and sex-matched HC participated in the study. Participants underwent a hypercapnia challenge, which included inhaling gas enriched in CO₂ to elicit a vasodilatory response while undergoing bold oxygen level-dependent (BOLD) MRI. We conducted cross-correlations to obtain the latency and degree of fit between the end-tidal CO₂ and the 1) average grey matter (GM) timeseries and 2) average CSF timeseries at the most inferior slice of the image acquisition. Permutation testing (reps = 10,000) was used to evaluate mean group differences between PD and HC in the fit and latency of cerebrovascular (ETCO₂-GM) and CSF reactivity (ETCO₂-CSF) to the CO₂ paradigm as well as the GM-CSF coupling (GM-CSF).

Results: Patients with PD (15.91 ± 2.00 SD) exhibited significantly delayed cerebrovascular reactivity relative to HC (13.03 ± 2.19; p < 0.001). Trend-level effects were observed whereby patients with PD exhibited reduced GM-CSF coupling (0.22 ± 0.07) relative to HC (0.25 ± 0.88; p = 0.09).

Conclusion: This preliminary analysis replicated our prior findings indicating patients with PD exhibited significantly delayed cerebrovascular reactivity. Additionally, trend-level effects suggest patients with PD exhibit reduced GM-CSF coupling, potentially reflecting reduced glymphatic clearance following a vasodilatory challenge. Future work is necessary to validate and improve our methodological approach to further evaluate to what extent delayed CVR may contribute to reduced CSF flux in PD.

References: [1] Y. Wang, P. van Gelderen, J.A. de Zwart, P.S. Özbay, H. Mandelkow, D. Picchioni, J.H. Duyn, Cerebrovascular activity is a major factor in the cerebrospinal fluid flow dynamics, Neuroimage. 258 (2022) 119362.
[2] N.E. Fultz, G. Bonmassar, K. Setsompop, R.A. Stickgold, B.R. Rosen, J.R. Polimeni, L.D. Lewis, Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep, Science (80-. ). 366 (2019) 628–631.
[3] S.G. Ryman, N. Shaff, A. Dodd, S. Nitschke, C. Wertz, K. Julio, G. Suarez Cedeno, A. Deligtisch, E. Erhardt, H. Lin, Reduced and Delayed Cerebrovascular Reactivity in Patients with Parkinson’s Disease, Mov. Disord. (2023).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebrovascular-reactivity-and-glymphatic-clearance-in-parkinsons-disease/