@article{9ab398a836424f929d53d50a08154bfc,
title = "Proteinopathy and longitudinal changes in functional connectivity networks in Parkinson disease",
abstract = "ObjectiveTo evaluate resting-state functional connectivity as a potential prognostic biomarker of Parkinson disease (PD) progression. The study examined longitudinal changes in cortical resting-state functional connectivity networks in participants with PD compared to controls as well as in relation to baseline protein measures and longitudinal clinical progression.MethodsIndividuals with PD without dementia (n = 64) and control participants (n = 27) completed longitudinal resting-state MRI scans and clinical assessments including full neuropsychological testing after overnight withdrawal of PD medications ({"}off{"}). A total of 55 participants with PD and 20 control participants also completed baseline β-amyloid PET scans and lumbar punctures for CSF protein levels of α-synuclein, β-amyloid, and tau. Longitudinal analyses were conducted with multilevel growth curve modeling, a type of mixed-effects model.ResultsFunctional connectivity within the sensorimotor network and the interaction between the dorsal attention network with the frontoparietal control network decreased significantly over time in participants with PD compared to controls. Baseline CSF α-synuclein protein levels predicted decline in the sensorimotor network. The longitudinal decline in the dorsal attention-frontoparietal internetwork strength correlated with the decline in cognitive function.ConclusionsThese results indicate that α-synuclein levels may influence longitudinal declines in motor-related functional connectivity networks. Further, the interaction between cortical association networks declines over time in PD prior to dementia onset and may serve as a prognostic marker for the development of dementia.",
author = "Campbell, {Meghan C.} and Jackson, {Joshua J.} and Koller, {Jonathan M.} and Snyder, {Abraham Z.} and Kotzbauer, {Paul T.} and Perlmutter, {Joel S.}",
note = "Funding Information: NINDS (NS097437, NS075321, NS097799, NS41509, NS058714, NS48924, P30 NS048056) and NIH NCRR (UL1RR024992); American Parkinson Disease Association (APDA) Advanced Research Center for PD at WUSTL; Greater St. Louis Chapter of the APDA; McDonnell Center for Systems Neuroscience; Barnes Jewish Hospital Foundation (Clinical Translational Research Award; Elliot Stein Family Fund; PD Research Fund). Funding Information: M.C. Campbell receives salary and research support from NIH, American Parkinson Disease Association (APDA) Advanced Research Center for PD at WUSTL, and Greater St. Louis Chapter of the APDA. J.J. Jackson receives salary and research support from NIH and Washington University. J.M. Koller receives salary and research support from NIH. A.Z. Snyder receives salary and research support from NIH. P.T. Kotzbauer receives salary and research support from NIH, Michael J. Fox Foundation, ALS Association, ALS Finding a Cure, INADcure Foundation, Jasper Valentijn Foundation, and Biogen. He also receives research and speaking fees from AbbVie and consulting fees from Merck. J.S. Perlmutter receives salary and research support from NIH, Washington University, APDA, Greater St. Louis Chapter of the APDA, McDonnell Center for Higher Brain Function, Barnes-Jewish Hospital Foundation, Huntington's Disease Society of America, CHDI, Michael J. Fox Foundation, Fixel Foundation, Oertli Foundation, and Riney Foundation. He also received honoraria from the American Academy of Neurology, Rochester, Emory, Parkinson Disease Foundation, Columbia, St Louis University, University of Pennsylvania, Harvard University, and University of Michigan. Go to https://n.neurology.org/lookup/doi/10.1212/WNL.0000000000008677 for full disclosures. Acknowledgment Publisher Copyright: {\textcopyright} American Academy of Neurology.",
year = "2020",
month = feb,
day = "18",
doi = "10.1212/WNL.0000000000008677",
language = "English",
volume = "94",
pages = "E718--E728",
journal = "Neurology",
issn = "0028-3878",
number = "7",
}