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.
Highlights
Idiopathic Parkinson’s disease (PD) is an age-related neurodegenerative disease that is characterized by motor symptoms of tremor, rigidity, and bradykinesia, as well as non-motor symptoms affecting sleep, cognition, and autonomic function [1]
We and others have described alterations of white matter microstructural integrity across various brain regions, including in frontal white matter and brainstem, in PD using diffusion tensor imaging (DTI) [9,10,11,12]—while DTI is sensitive to alterations of myelin, it is sensitive to other white matter microstructural changes [13,14]
PD and control subjects were recruited through local movement disorders clinics and the Wisconsin Alzheimer’s Disease Research Center (ADRC) as part of a longitudinal MRI study of PD sponsored by the Department of Veterans Affairs, CS R&D
Summary
Idiopathic Parkinson’s disease (PD) is an age-related neurodegenerative disease that is characterized by motor symptoms of tremor, rigidity, and bradykinesia, as well as non-motor symptoms affecting sleep, cognition, and autonomic function [1]. We and others have described alterations of white matter microstructural integrity across various brain regions, including in frontal white matter and brainstem, in PD using diffusion tensor imaging (DTI) [9,10,11,12]—while DTI is sensitive to alterations of myelin, it is sensitive to other white matter microstructural changes [13,14].
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