title: Longitudinal changes in free-water within the substantia nigra of Parkinson's disease.
abstract: There is a clear need to develop non-invasive markers of substantia nigra progression in Parkinson's disease. We previously found elevated free-water levels in the substantia nigra for patients with Parkinson's disease compared with controls in single-site and multi-site cohorts. Here, we test the hypotheses that free-water levels in the substantia nigra of Parkinson's disease increase following 1 year of progression, and that baseline free-water levels in the substantia nigra predict the change in bradykinesia following 1 year. We conducted a longitudinal study in controls (n = 19) and patients with Parkinson's disease (n = 25). Diffusion imaging and clinical data were collected at baseline and after 1 year. Free-water analyses were performed on diffusion imaging data using blinded, hand-drawn regions of interest in the posterior substantia nigra. A group effect indicated free-water values were increased in the posterior substantia nigra of patients with Parkinson's disease compared with controls (P = 0.003) and we observed a significant group × time interaction (P < 0.05). Free-water values increased for the Parkinson's disease group after 1 year (P = 0.006), whereas control free-water values did not change. Baseline free-water values predicted the 1 year change in bradykinesia scores (r = 0.74, P < 0.001) and 1 year change in Montreal Cognitive Assessment scores (r = -0.44, P = 0.03). Free-water in the posterior substantia nigra is elevated in Parkinson's disease, increases with progression of Parkinson's disease, and predicts subsequent changes in bradykinesia and cognitive status over 1 year. These findings demonstrate that free-water provides a potential non-invasive progression marker of the substantia nigra.
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Ofori
authors.affiliation: 2 Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, USA.
authors.forename: Ofer
authors.initials: O
authors.lastname: Pasternak
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA.
authors.forename: Peggy J
authors.initials: PJ
authors.lastname: Planetta
authors.affiliation: 3 Department of Preventative Medicine, Rush University Medical Centre, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA.
authors.forename: Roxana G
authors.initials: RG
authors.lastname: Burciu
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA.
authors.forename: Amy F
authors.initials: AF
authors.lastname: Snyder
authors.affiliation: 4 Department of Radiation Oncology, University of Florida, USA 5 Human Imaging Core, Clinical and Translational Science Institute, University of Florida, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Lai
authors.affiliation: 6 Department of Neurology and Centre for Movement Disorders and Neurorestoration, University of Florida, USA 7 Departments of Neurosurgery, Psychiatry, and History, University of Florida, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.affiliation: 1 Department of Applied Physiology and Kinesiology, University of Florida, USA 6 Department of Neurology and Centre for Movement Disorders and Neurorestoration, University of Florida, USA 8 Department of Biomedical Engineering, University of Florida, USA vcourt@ufl.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Vaillancourt
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology*; D014867:Water / Q000378:metabolism*
chemical_list: D014867:Water
keywords: Parkinson’s disease; diffusion MRI; extracellular space; longitudinal; substantia nigra