Reduced and Delayed Cerebrovascular Reactivity in Patients with Parkinson's Disease

Overview

Journal Mov Disord

Date 2023 May 8

PMID 37157056

Authors

Sephira G Ryman

Nicholas Shaff

Andrew Dodd

Stephanie Nitschke

Christopher Wertz

Kayla Julio

Gerson Suarez Cedeno

Amanda Deligtisch

Erik Erhardt

Henry Lin

Andrei Vakhtin

Kathleen L Poston

Rawan Tarawneh

Sarah Pirio Richardson

Andrew Mayer

Affiliations

Soon will be listed here.

Abstract

Background: Cerebrovascular dysfunction in Parkinson's disease (PD) is heterogeneous and may contribute to disease pathophysiology or progression. There is a need to understand the mechanisms by which cerebrovascular dysfunction is altered in participants with PD.

Objectives: The objective of this study is to test the hypothesis that participants with PD exhibit a significant reduction in the ability of the cerebral vessels to dilate in response to vasoactive challenges relative to healthy controls (HC).

Methods: The current study uses a vasodilatory challenge while participants undergo functional magnetic resonance imaging to quantify the amplitude and delay of cerebrovascular reactivity in participants with PD relative to age and sex-matched HC. An analysis of covariance was used to evaluate differences in cerebrovascular reactivity amplitude and latency between PD participants and HC.

Results: A significant main effect of group was observed for whole-brain cerebrovascular reactivity amplitude (F = 4.38, p = 0.046, Hedge's g = 0.73) and latency (F = 16.35, p < 0.001, Hedge's g = 1.42). Participants with PD exhibited reduced whole-brain amplitude and increased latencies in cerebrovascular reactivity relative to HC. The evaluation of regional effects indicates that the largest effects were observed in the cuneus, precuneus, and parietal regions.

Conclusions: PD participants exhibited reduced and delayed cerebrovascular reactivity. This dysfunction may play an important role in chronic hypoxia, neuroinflammation, and protein aggregation, mechanisms that could lead to disease progression. Cerebrovascular reactivity may serve as an important biomarker and target for future interventions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Citing Articles

Variable Cerebral Blood Flow Responsiveness to Acute Hypoxic Hypoxia.

Johnson H, Wang M, Stickland R, Chen Y, Parrish T, Sorond F bioRxiv. 2024; .

PMID: 39605678 PMC: 11601454. DOI: 10.1101/2024.11.14.623430.

Abnormal Cerebrovascular Activity, Perfusion, and Glymphatic Clearance in Lewy Body Diseases.

Ryman S, Vakhtin A, Mayer A, van der Horn H, Shaff N, Nitschke S Mov Disord. 2024; 39(8):1258-1268.

PMID: 38817039 PMC: 11341260. DOI: 10.1002/mds.29867.

Parkinson's disease cerebrovascular reactivity pattern: A feasibility study.

van der Horn H, Vakhtin A, Julio K, Nitschke S, Shaff N, Dodd A J Cereb Blood Flow Metab. 2024; 44(10):1774-1786.

PMID: 38578669 PMC: 11494834. DOI: 10.1177/0271678X241241895.

References

Ma Y, Huang C, Dyke J, Pan H, Alsop D, Feigin A . Parkinson's disease spatial covariance pattern: noninvasive quantification with perfusion MRI. J Cereb Blood Flow Metab. 2010; 30(3):505-9. PMC: 2949137. DOI: 10.1038/jcbfm.2009.256. View

Christopher L, Marras C, Duff-Canning S, Koshimori Y, Chen R, Boileau I . Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson's disease with mild cognitive impairment. Brain. 2013; 137(Pt 2):565-75. PMC: 4454524. DOI: 10.1093/brain/awt337. View

Hou X, Liu P, Li Y, Jiang D, De Vis J, Lin Z . The association between BOLD-based cerebrovascular reactivity (CVR) and end-tidal CO in healthy subjects. Neuroimage. 2019; 207:116365. PMC: 8080082. DOI: 10.1016/j.neuroimage.2019.116365. View

Gibbons C, Schmidt P, Biaggioni I, Frazier-Mills C, Freeman R, Isaacson S . The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol. 2017; 264(8):1567-1582. PMC: 5533816. DOI: 10.1007/s00415-016-8375-x. View

Al-Bachari S, Parkes L, Vidyasagar R, Hanby M, Tharaken V, Leroi I . Arterial spin labelling reveals prolonged arterial arrival time in idiopathic Parkinson's disease. Neuroimage Clin. 2014; 6:1-8. PMC: 4215519. DOI: 10.1016/j.nicl.2014.07.014. View

Owen A, James M, Leigh P, Summers B, Marsden C, Quinn N . Fronto-striatal cognitive deficits at different stages of Parkinson's disease. Brain. 1992; 115 ( Pt 6):1727-51. DOI: 10.1093/brain/115.6.1727. View

Jones J, Jacobson C, Murphy M, Price C, Okun M, Bowers D . Influence of hypertension on neurocognitive domains in nondemented Parkinson's disease patients. Parkinsons Dis. 2014; 2014:507529. PMC: 3920751. DOI: 10.1155/2014/507529. View

Fernandez-Seara M, Mengual E, Vidorreta M, Aznarez-Sanado M, Loayza F, Villagra F . Cortical hypoperfusion in Parkinson's disease assessed using arterial spin labeled perfusion MRI. Neuroimage. 2011; 59(3):2743-50. DOI: 10.1016/j.neuroimage.2011.10.033. View

Pelizzari L, Lagana M, Rossetto F, Bergsland N, Galli M, Baselli G . Cerebral blood flow and cerebrovascular reactivity correlate with severity of motor symptoms in Parkinson's disease. Ther Adv Neurol Disord. 2019; 12:1756286419838354. PMC: 6431769. DOI: 10.1177/1756286419838354. View

10.

Ashburner J, Friston K . Unified segmentation. Neuroimage. 2005; 26(3):839-51. DOI: 10.1016/j.neuroimage.2005.02.018. View

11.

Suo X, Lei D, Cheng L, Li N, Zuo P, Wang D . Multidelay multiparametric arterial spin labeling perfusion MRI and mild cognitive impairment in early stage Parkinson's disease. Hum Brain Mapp. 2018; 40(4):1317-1327. PMC: 6865659. DOI: 10.1002/hbm.24451. View

12.

Thomas B, Liu P, Park D, van Osch M, Lu H . Cerebrovascular reactivity in the brain white matter: magnitude, temporal characteristics, and age effects. J Cereb Blood Flow Metab. 2013; 34(2):242-7. PMC: 3915204. DOI: 10.1038/jcbfm.2013.194. View

13.

Pauli W, Nili A, Michael Tyszka J . A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei. Sci Data. 2018; 5:180063. PMC: 5903366. DOI: 10.1038/sdata.2018.63. View

14.

Liu P, De Vis J, Lu H . Cerebrovascular reactivity (CVR) MRI with CO2 challenge: A technical review. Neuroimage. 2018; 187:104-115. PMC: 6150860. DOI: 10.1016/j.neuroimage.2018.03.047. View

15.

Fisher J . The CO2 stimulus for cerebrovascular reactivity: Fixing inspired concentrations vs. targeting end-tidal partial pressures. J Cereb Blood Flow Metab. 2016; 36(6):1004-11. PMC: 4908627. DOI: 10.1177/0271678X16639326. View

16.

Kamagata K, Motoi Y, Hori M, Suzuki M, Nakanishi A, Shimoji K . Posterior hypoperfusion in Parkinson's disease with and without dementia measured with arterial spin labeling MRI. J Magn Reson Imaging. 2011; 33(4):803-7. DOI: 10.1002/jmri.22515. View

17.

Tomlinson C, Stowe R, Patel S, Rick C, Gray R, Clarke C . Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord. 2010; 25(15):2649-53. DOI: 10.1002/mds.23429. View

18.

Madhyastha T, Askren M, Boord P, Zhang J, Leverenz J, Grabowski T . Cerebral perfusion and cortical thickness indicate cortical involvement in mild Parkinson's disease. Mov Disord. 2015; 30(14):1893-900. PMC: 4567553. DOI: 10.1002/mds.26128. View

19.

Ashby J, Mack J . Endothelial Control of Cerebral Blood Flow. Am J Pathol. 2021; 191(11):1906-1916. DOI: 10.1016/j.ajpath.2021.02.023. View

20.

Pilotto A, Turrone R, Liepelt-Scarfone I, Bianchi M, Poli L, Borroni B . Vascular Risk Factors and Cognition in Parkinson's Disease. J Alzheimers Dis. 2016; 51(2):563-70. DOI: 10.3233/JAD-150610. View