Feng Han1, Gregory L Brown2,3, Yalin Zhu1, Aaron E Belkin-Rosen1, Mechelle M Lewis3,4, Guangwei Du3, Yameng Gu1, Paul J Eslinger3,5, Richard B Mailman3,4, Xuemei Huang3,4,5,6,7,8, Xiao Liu1,8. 1. Department of Biomedical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA. 2. Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, USA. 3. Department of Neurology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 4. Department of Pharmacology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 5. Department of Radiology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 6. Department of Neurosurgery, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 7. Department of Kinesiology, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 8. Institute for Computational and Data Sciences, The Pennsylvania State University, University Park, Pennsylvania, USA.
Abstract
BACKGROUND: Deposition and spreading of misfolded proteins (α-synuclein and tau) have been linked to Parkinson's disease 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, which may reflect glymphatic function. OBJECTIVE: The objective of this current study was to determine if the decoupling of brain activity-CSF flow is linked to Parkinson's disease 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 disease and 58 control subjects. Parkinson's disease patients were subgrouped into those with mild cognitive impairment (MoCA < 26), n = 31, and those without mild cognitive impairment (MoCA ≥ 26), n = 29. The coupling strength between the resting-state global blood-oxygen-level-dependent signal and associated CSF flow was quantified, compared among groups, and associated with clinical and structural measurements. RESULTS: Global blood-oxygen-level-dependent signal-CSF coupling decreased significantly (P < 0.006) in Parkinson's disease patients showing mild cognitive impairment, compared with those without mild cognitive impairment and controls. Reduced global blood-oxygen-level-dependent signal-CSF coupling was associated with decreased MoCA scores present in Parkinson's disease patients (P = 0.005) but not in controls (P = 0.65). Weaker global blood-oxygen-level-dependent signal-CSF coupling in Parkinson's disease 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 disease. CONCLUSIONS: The decoupling between global brain activity and associated CSF flow is related to Parkinson's disease cognitive impairment.
BACKGROUND: Deposition and spreading of misfolded proteins (α-synuclein and tau) have been linked to Parkinson's disease 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, which may reflect glymphatic function. OBJECTIVE: The objective of this current study was to determine if the decoupling of brain activity-CSF flow is linked to Parkinson's disease 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 disease and 58 control subjects. Parkinson's disease patients were subgrouped into those with mild cognitive impairment (MoCA < 26), n = 31, and those without mild cognitive impairment (MoCA ≥ 26), n = 29. The coupling strength between the resting-state global blood-oxygen-level-dependent signal and associated CSF flow was quantified, compared among groups, and associated with clinical and structural measurements. RESULTS: Global blood-oxygen-level-dependent signal-CSF coupling decreased significantly (P < 0.006) in Parkinson's disease patients showing mild cognitive impairment, compared with those without mild cognitive impairment and controls. Reduced global blood-oxygen-level-dependent signal-CSF coupling was associated with decreased MoCA scores present in Parkinson's disease patients (P = 0.005) but not in controls (P = 0.65). Weaker global blood-oxygen-level-dependent signal-CSF coupling in Parkinson's disease 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 disease. CONCLUSIONS: The decoupling between global brain activity and associated CSF flow is related to Parkinson's disease cognitive impairment.
Authors: Heiko Braak; Kelly Del Tredici; Udo Rüb; Rob A I de Vos; Ernst N H Jansen Steur; Eva Braak Journal: Neurobiol Aging Date: 2003 Mar-Apr Impact factor: 4.673
Authors: Jonathan D Power; Kelly A Barnes; Abraham Z Snyder; Bradley L Schlaggar; Steven E Petersen Journal: Neuroimage Date: 2011-10-14 Impact factor: 6.556
Authors: David J Irwin; Murray Grossman; Daniel Weintraub; Howard I Hurtig; John E Duda; Sharon X Xie; Edward B Lee; Vivianna M Van Deerlin; Oscar L Lopez; Julia K Kofler; Peter T Nelson; Gregory A Jicha; Randy Woltjer; Joseph F Quinn; Jeffery Kaye; James B Leverenz; Debby Tsuang; Katelan Longfellow; Dora Yearout; Walter Kukull; C Dirk Keene; Thomas J Montine; Cyrus P Zabetian; John Q Trojanowski Journal: Lancet Neurol Date: 2017-01 Impact factor: 44.182
Authors: Susanne J van Veluw; Steven S Hou; Maria Calvo-Rodriguez; Michal Arbel-Ornath; Austin C Snyder; Matthew P Frosch; Steven M Greenberg; Brian J Bacskai Journal: Neuron Date: 2019-12-03 Impact factor: 17.173
Authors: Yicun Wang; Peter van Gelderen; Jacco A de Zwart; Pinar S Özbay; Hendrik Mandelkow; Dante Picchioni; Jeff H Duyn Journal: Neuroimage Date: 2022-06-08 Impact factor: 7.400