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    Functional magnetic resonance imaging biomarkers predicting cognitive progression in Parkinson disease: protocol for a prospective longitudinal cohort study

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    Author
    Hanna-Pladdy, B.
    Gullapalli, R.
    Chen, H.
    Date
    2019
    Journal
    Journal of Medical Internet Research
    Publisher
    Journal of Medical Internet Research
    Type
    article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.2196/12870
    Abstract
    Background: Cardinal features of Parkinson disease (PD) are motor symptoms, but nonmotor features such as mild cognitive impairment (MCI) are common early in the disease process. MCI can progress and convert to dementia in advanced stages, creating significant disability and reduced quality of life. The primary pathological substrate for cognitive decline in PD is unclear, and there are no reliable biomarkers predicting the risk of conversion to dementia. A subgroup of PD patients with visual hallucinations may display more rapid conversion to dementia, suggesting that regional markers of visuoperceptual dysfunction may be sensitive to pathologic density in posterior cortical regions. Objective: The purpose of this project is to characterize PD-MCI and evaluate the utility of genetic and neuroimaging biomarkers in predicting cognitive outcomes with a prospective longitudinal study. We will evaluate whether accelerated cognitive progression may be reflected in biomarkers of early posterior cortical changes reflective of α-synuclein deposition. Methods: We will evaluate a cohort of early-stage PD patients with the following methods to predict cognitive progression: (1) serial neuropsychological evaluations including detailed visuoperceptual functioning across 4 years; (2) genetic analysis of SNCA (α-synuclein), MAPT (microtubule-associated tau), and APOE (apolipoprotein E); (3) an event-related functional magnetic resonance imaging paradigm of object recognition memory; and (4) anatomical and regional brain activation changes (resting-state functional magnetic resonance imaging) across 4 years. Results: The project received funding from the National Institutes of Health in August 2017, and data collection began in February 2018. Enrollment is ongoing, and subjects will be evaluated annually for 4 years extended across a 5-year project including data analysis and image processing. Conclusions: Cognitive, genetic, and structural and functional magnetic resonance imaging will characterize neural network changes predictive of cognitive progression in PD across 4 years. Identification of biomarkers with sensitivity for early prediction and estimation of risk for conversion to dementia in PD will pave the way for effective intervention with neuroprotective therapies during the critical stage when treatment can have the greatest impact.
    Sponsors
    This project is funded by the National Institutes of Health (BHP R01NS098249) under administrative institutional guidance from the National Institute of Neurological Disorders and Stroke and funding provided by the National Institute of Aging.
    Keyword
    Biomarkers
    Cognition
    Dementia
    Disease progression
    Functional neuroimaging
    Mild cognitive impairment
    Parkinson disease
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85067834812&doi=10.2196%2f12870&partnerID=40&md5=ac359bb232f27414cdfc074ae2f4b9dd; http://hdl.handle.net/10713/10221
    ae974a485f413a2113503eed53cd6c53
    10.2196/12870
    Scopus Count
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    UMB Open Access Articles 2019

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