Meghan C Campbell1, Joshua J Jackson2, Jonathan M Koller2, Abraham Z Snyder2, Paul T Kotzbauer2, Joel S Perlmutter2. 1. From the Departments of Neurology (M.C.C., A.Z.S., P.T.K., J.S.P.), Radiology (M.C.C., A.Z.S., J.S.P.), Psychiatry (J.M.K.), and Neuroscience (J.S.P.), Program in Occupational Therapy (J.S.P.), and Program in Physical Therapy (J.S.P.), Washington University School of Medicine; and Department of Psychological and Brain Sciences (J.J.J.), Washington University in St. Louis, MO. meghanc@wustl.edu. 2. From the Departments of Neurology (M.C.C., A.Z.S., P.T.K., J.S.P.), Radiology (M.C.C., A.Z.S., J.S.P.), Psychiatry (J.M.K.), and Neuroscience (J.S.P.), Program in Occupational Therapy (J.S.P.), and Program in Physical Therapy (J.S.P.), Washington University School of Medicine; and Department of Psychological and Brain Sciences (J.J.J.), Washington University in St. Louis, MO.
Abstract
OBJECTIVE: To 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. METHODS: Individuals 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. RESULTS: Functional 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. CONCLUSIONS: These 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.
OBJECTIVE: To 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. METHODS: Individuals 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. RESULTS: Functional 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. CONCLUSIONS: These 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.
Authors: Nico U F Dosenbach; Damien A Fair; Francis M Miezin; Alexander L Cohen; Kristin K Wenger; Ronny A T Dosenbach; Michael D Fox; Abraham Z Snyder; Justin L Vincent; Marcus E Raichle; Bradley L Schlaggar; Steven E Petersen Journal: Proc Natl Acad Sci U S A Date: 2007-06-18 Impact factor: 11.205
Authors: Liang Wang; Matthew R Brier; Abraham Z Snyder; Jewell B Thomas; Anne M Fagan; Chengjie Xiong; Tammie L Benzinger; David M Holtzman; John C Morris; Beau M Ances Journal: JAMA Neurol Date: 2013-10 Impact factor: 18.302
Authors: Matthew L Dixon; Alejandro De La Vega; Caitlin Mills; Jessica Andrews-Hanna; R Nathan Spreng; Michael W Cole; Kalina Christoff Journal: Proc Natl Acad Sci U S A Date: 2018-01-30 Impact factor: 11.205
Authors: Anne Hafkemeijer; Christiane Möller; Elise G P Dopper; Lize C Jiskoot; Annette A van den Berg-Huysmans; John C van Swieten; Wiesje M van der Flier; Hugo Vrenken; Yolande A L Pijnenburg; Frederik Barkhof; Philip Scheltens; Jeroen van der Grond; Serge A R B Rombouts Journal: J Alzheimers Dis Date: 2017 Impact factor: 4.472
Authors: R Nathan Spreng; Jorge Sepulcre; Gary R Turner; W Dale Stevens; Daniel L Schacter Journal: J Cogn Neurosci Date: 2012-08-20 Impact factor: 3.225
Authors: Mathew R Brier; Jewell B Thomas; Abraham Z Snyder; Tammie L Benzinger; Dongyang Zhang; Marcus E Raichle; David M Holtzman; John C Morris; Beau M Ances Journal: J Neurosci Date: 2012-06-27 Impact factor: 6.167
Authors: Carmen Gasca-Salas; Ainara Estanga; Pedro Clavero; Isabel Aguilar-Palacio; Rafael González-Redondo; Jose A Obeso; Maria C Rodríguez-Oroz Journal: J Parkinsons Dis Date: 2014 Impact factor: 5.568
Authors: Pardis Zarifkar; Jeehyun Kim; Christian La; Kai Zhang; Sophie YorkWilliams; Taylor F Levine; Lu Tian; Per Borghammer; Kathleen L Poston Journal: Parkinsonism Relat Disord Date: 2021-01-12 Impact factor: 4.402
Authors: Laura Ibanez; Jorge A Bahena; Chengran Yang; Umber Dube; Fabiana H G Farias; John P Budde; Kristy Bergmann; Carol Brenner-Webster; John C Morris; Richard J Perrin; Nigel J Cairns; John O'Donnell; Ignacio Álvarez; Monica Diez-Fairen; Miquel Aguilar; Rebecca Miller; Albert A Davis; Pau Pastor; Paul Kotzbauer; Meghan C Campbell; Joel S Perlmutter; Herve Rhinn; Oscar Harari; Carlos Cruchaga; Bruno A Benitez Journal: Acta Neuropathol Commun Date: 2020-11-19 Impact factor: 7.801