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Decoupling of global brain activity and cerebrospinal fluid flow in Parkinson’s cognitive decline

Feng Han, Gregory L. Brown, Yalin Zhu, Aaron E. Belkin-Rosen, Mechelle M. Lewis, Guangwei Du, Yameng Gu, Paul J. Eslinger, Richard B. Mailman, Xuemei Huang, Xiao Liu
doi: https://doi.org/10.1101/2021.01.08.425953
Feng Han
1Department of Biomedical Engineering, The Pennsylvania State University, PA, USA
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Gregory L. Brown
2Department of Engineering Science and Mechanics, The Pennsylvania State University, PA, USA
3Department of Neurology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
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Yalin Zhu
1Department of Biomedical Engineering, The Pennsylvania State University, PA, USA
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Aaron E. Belkin-Rosen
1Department of Biomedical Engineering, The Pennsylvania State University, PA, USA
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Mechelle M. Lewis
3Department of Neurology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
4Department of Pharmacology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
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Guangwei Du
3Department of Neurology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
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Yameng Gu
1Department of Biomedical Engineering, The Pennsylvania State University, PA, USA
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Paul J. Eslinger
3Department of Neurology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
5Department of Radiology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
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Richard B. Mailman
3Department of Neurology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
4Department of Pharmacology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
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Xuemei Huang
3Department of Neurology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
4Department of Pharmacology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
5Department of Radiology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
6Department of Neurosurgery, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
7Department of Kinesiology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA, USA
8Institute for Computational and Data Sciences, The Pennsylvania State University, PA, USA
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  • For correspondence: xxl213@engr.psu.edu xuemei@psu.edu
Xiao Liu
1Department of Biomedical Engineering, The Pennsylvania State University, PA, USA
8Institute for Computational and Data Sciences, The Pennsylvania State University, PA, USA
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  • For correspondence: xxl213@engr.psu.edu xuemei@psu.edu
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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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 09, 2021.
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Decoupling of global brain activity and cerebrospinal fluid flow in Parkinson’s cognitive decline
Feng Han, Gregory L. Brown, Yalin Zhu, Aaron E. Belkin-Rosen, Mechelle M. Lewis, Guangwei Du, Yameng Gu, Paul J. Eslinger, Richard B. Mailman, Xuemei Huang, Xiao Liu
bioRxiv 2021.01.08.425953; doi: https://doi.org/10.1101/2021.01.08.425953
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Decoupling of global brain activity and cerebrospinal fluid flow in Parkinson’s cognitive decline
Feng Han, Gregory L. Brown, Yalin Zhu, Aaron E. Belkin-Rosen, Mechelle M. Lewis, Guangwei Du, Yameng Gu, Paul J. Eslinger, Richard B. Mailman, Xuemei Huang, Xiao Liu
bioRxiv 2021.01.08.425953; doi: https://doi.org/10.1101/2021.01.08.425953

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