Cognitive impairment in Parkinson's disease is associated with Default Mode Network subsystem connectivity and cerebrospinal fluid Aβ

TY - JOUR

T1 - Cognitive impairment in Parkinson's disease is associated with Default Mode Network subsystem connectivity and cerebrospinal fluid Aβ

AU - Zarifkar, Pardis

AU - Kim, Jeehyun

AU - La, Christian

AU - Zhang, Kai

AU - YorkWilliams, Sophie

AU - Levine, Taylor F

AU - Tian, Lu

AU - Borghammer, Per

AU - Poston, Kathleen L

N1 - Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2021/2

Y1 - 2021/2

N2 - INTRODUCTION: To identify clinically implementable biomarkers of cognitive impairment in Parkinson's Disease (PD) derived from resting state-functional MRI (rs-fMRI) and CSF protein analysis.METHODS: In this single-center longitudinal cohort study, we analyzed rs-fMRI and CSF biomarkers from 50 PD patients (23 cognitively normal, 18 mild cognitive impairment, 9 dementia) and 19 controls, who completed comprehensive neuropsychological testing. A subgroup of participants returned for follow-up cognitive assessments three years later. From rs-fMRI, we studied the connectivity within two distinct Default Mode Network subsystems: left-to-right hippocampus (LHC-RHC) and medial prefrontal cortex-to-posterior cingulate cortex (mPFC-PCC). We used regression analyses to determine whether imaging (LHC-RHC, mPFC-PCC), clinical (CSF Aβ-42:40, disease duration), and demographic (age, sex, education) variables were associated with global and domain-specific cognitive impairments.RESULTS: LHC-RHC (F3,67 = 3.41,p=0.023) and CSF Aβ-42:40 (χ2(3) = 8.77,p = 0.033) were reduced across more cognitively impaired PD groups. Notably, LHC-RHC connectivity was significantly associated with all global and domain-specific cognitive impairments (attention/executive, episodic memory, visuospatial, and language) at the baseline visit. In an exploratory longitudinal analysis, mPFC-PCC was associated with future global and episodic memory impairment.CONCLUSION: We used biomarker techniques that are readily available in clinical and research facilities to shed light on the pathophysiologic basis of cognitive impairment in PD. Our findings suggest that there is a functionally distinct role of the hippocampal subsystem within the DMN resting state network, and that intrinsic connectivity between the hippocampi is critically related to a broad range of cognitive functions in PD.

AB - INTRODUCTION: To identify clinically implementable biomarkers of cognitive impairment in Parkinson's Disease (PD) derived from resting state-functional MRI (rs-fMRI) and CSF protein analysis.METHODS: In this single-center longitudinal cohort study, we analyzed rs-fMRI and CSF biomarkers from 50 PD patients (23 cognitively normal, 18 mild cognitive impairment, 9 dementia) and 19 controls, who completed comprehensive neuropsychological testing. A subgroup of participants returned for follow-up cognitive assessments three years later. From rs-fMRI, we studied the connectivity within two distinct Default Mode Network subsystems: left-to-right hippocampus (LHC-RHC) and medial prefrontal cortex-to-posterior cingulate cortex (mPFC-PCC). We used regression analyses to determine whether imaging (LHC-RHC, mPFC-PCC), clinical (CSF Aβ-42:40, disease duration), and demographic (age, sex, education) variables were associated with global and domain-specific cognitive impairments.RESULTS: LHC-RHC (F3,67 = 3.41,p=0.023) and CSF Aβ-42:40 (χ2(3) = 8.77,p = 0.033) were reduced across more cognitively impaired PD groups. Notably, LHC-RHC connectivity was significantly associated with all global and domain-specific cognitive impairments (attention/executive, episodic memory, visuospatial, and language) at the baseline visit. In an exploratory longitudinal analysis, mPFC-PCC was associated with future global and episodic memory impairment.CONCLUSION: We used biomarker techniques that are readily available in clinical and research facilities to shed light on the pathophysiologic basis of cognitive impairment in PD. Our findings suggest that there is a functionally distinct role of the hippocampal subsystem within the DMN resting state network, and that intrinsic connectivity between the hippocampi is critically related to a broad range of cognitive functions in PD.

KW - Biomarkers

KW - CSF

KW - Default mode network

KW - Dementia

KW - Mild cognitive impairment

KW - Parkinson's disease/Parkinsonism

KW - rs-fMRI

UR - https://www.scopus.com/pages/publications/85099633527

U2 - 10.1016/j.parkreldis.2021.01.002

DO - 10.1016/j.parkreldis.2021.01.002

M3 - Journal article

C2 - 33484978

SN - 1353-8020

VL - 83

SP - 71

EP - 78

JO - Parkinsonism & Related Disorders

JF - Parkinsonism & Related Disorders

ER -