title: Alterations of Myelin Content in Parkinson's Disease: A Cross-Sectional Neuroimaging Study.
abstract: Alterations to myelin may be a core pathological feature of neurodegenerative diseases. Although white matter microstructural differences have been described in Parkinson's disease (PD), it is unknown whether such differences include alterations of the brain's myelin content. Thus, the objective of the current study is to measure and compare brain myelin content between PD patients and age-matched controls. In this cross-sectional study, 63 participants from the Longitudinal MRI in Parkinson's Disease study underwent brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) scoring, and cognitive asessments. Subjects were imaged with the mcDEPSOT (multi-component driven equilibrium single pulse observation of T1 and T2), a multicomponent relaxometry technique that quantifies longitudinal and transverse relaxation rates (R1 and R2, respectively) and the myelin water fraction (VFM), a surrogate for myelin content. A voxel-wise approach was used to compare R1, R2, and VFM measures between PD and control groups, and to evaluate relationships with age as well as disease duration, UPDRS scores, and daily levodopa equivalent dose. PD subjects had higher VFM than controls in frontal and temporal white matter and bilateral thalamus. Greater age was strongly associated with lower VFM in both groups, while an age-by-group interaction suggested a slower rate of VFM decline in the left putamen with aging in PD. Within the PD group, measures of disease severity, including UPDRS, daily levodopa equivalent dose, and disease duration, were observed to be related with myelin content in diffuse brain regions. The age-by-group interaction suggests that either PD or dopaminergic therapies allay observed age-related myelin changes. The relationships between VFM and disease severity measures suggests that VFM may provide a surrogate marker for microstructural changes related to Parkinson's disease.
authors.affiliation: Waisman Center, University of Wisconsin Madison, Madison, Wisconsin, United States of America.
authors.forename: Douglas C
authors.identifier: http://orcid.org/0000-0002-7057-1285
authors.initials: DC
authors.lastname: Dean
authors.affiliation: William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, United States of America.|Department of Neurology, University of Wisconsin Madison, Madison, Wisconsin, United States of America.
authors.forename: Jitka
authors.initials: J
authors.lastname: Sojkova
authors.affiliation: Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, Oxfordshire, United Kingdom.
authors.forename: Samuel
authors.initials: S
authors.lastname: Hurley
authors.affiliation: Waisman Center, University of Wisconsin Madison, Madison, Wisconsin, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Kecskemeti
authors.affiliation: Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Ozioma
authors.initials: O
authors.lastname: Okonkwo
authors.affiliation: Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Bendlin
authors.affiliation: William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, United States of America.|Department of Neurology, University of Wisconsin Madison, Madison, Wisconsin, United States of America.
authors.forename: Frances
authors.initials: F
authors.lastname: Theisen
authors.affiliation: William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, United States of America.|Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
authors.affiliation: Waisman Center, University of Wisconsin Madison, Madison, Wisconsin, United States of America.|Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.|Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Alexander
authors.affiliation: William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, United States of America.|Department of Neurology, University of Wisconsin Madison, Madison, Wisconsin, United States of America.|Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Gallagher
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009186:Myelin Sheath / Q000473:pathology*; D059906:Neuroimaging / Q000379:methods*; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa