White matter microstructure in Parkinson’s disease with and without elevated REM sleep muscle tone

The mechanisms contributing to increased expression of motor and cognitive impairment in people with Parkinson9s disease who lack muscle atonia during rapid eye movement (REM) sleep compared to those with muscle atonia are poorly understood. This study used tract-based spatial statistics to compare diffusion measures of white matter microstructure between people with Parkinson9s disease with and without REM sleep without atonia as well as the relationships of these measures to motor and cognitive function. Thirty-eight individuals with mild-to-moderate Parkinson9s disease and twenty-one matched control subjects underwent ultra-high-field MRI (7Tesla), quantitative motor assessments of gait and bradykinesia, and neuropsychological testing. The Parkinson9s disease cohort was separated post-hoc into those with and without elevated chin or leg muscle activity during REM sleep based on polysomnography findings. Fractional anisotropy was significantly higher, and radial and mean diffusivity significantly lower, in diffuse regions of the corpus callosum, projection, and association white matter pathways in the Parkinson9s group with normal REM sleep compared to controls. In contrast, there was no significant difference in fractional anisotropy between the Parkinson9s group with elevated muscle tone and controls. Fractional anisotropy was also significantly higher in a subset of pathways in the Parkinson9s disease group with normal REM sleep muscle tone compared to those with elevated REM sleep muscle tone. The group with elevated REM sleep muscle tone had significant impairments in gait and upper arm speed compared to controls and significantly worse scores in specific cognitive domains (executive function, visuospatial memory) compared to the Parkinson9s disease group with normal REM sleep muscle tone. Regression analyses showed that gait speed and step length in the Parkinson9s disease cohort were predicted by measures of mean fractional anisotropy of the anterior corona radiata, whereas elbow flexion velocity was predicted by fractional anisotropy of the superior corona radiata. Visuospatial memory task performance was predicted by the radial diffusivity of the posterior corona radiata. These findings demonstrate that people with mild-to-moderate severity of Parkinson9s disease who have normal muscle tone during REM sleep show alterations in white matter microstructure that are associated with preserved motor and cognitive function, but these adaptations are reduced or absent in those with increased REM sleep motor tone.