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  • Title: Cognitive impairment in Parkinson's disease is associated with Default Mode Network subsystem connectivity and cerebrospinal fluid Aβ.
    Author: Zarifkar P, Kim J, La C, Zhang K, YorkWilliams S, Levine TF, Tian L, Borghammer P, Poston KL.
    Journal: Parkinsonism Relat Disord; 2021 Feb; 83():71-78. PubMed ID: 33484978.
    Abstract:
    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.
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