White matter changes in drug-naïve Parkinson's disease patients with impulse control & probable REM sleep behavior disorders.

Background: According to epidemiological studies, Parkinson's disease (PD) patients with probable REM sleep behavior disorder (pRBD) are more prone to develop impulse control disorders (ICDs), which is shown to be present in drug-naïve PD patients, and vice versa.

Objectives: To investigate white-matter integrity differences, with and without comorbid pRBD and ICDs.

Methods: 149 de-novo PD patients and 30 age- and gender-matched controls from the Parkinson's Progression Markers Initiative were studied. PD subjects were categorized into four groups with and without these comorbidities. We investigated the white matter integrity differences between these groups.

Results: PDs with only ICDs manifested greater fractional anisotropy (FA) and lower mean diffusivity (MD) in ipsilateral cerebellar connections when compared to controls and to Parkinson's with both comorbid disorders. In contrast, significantly lower FA and higher MD in the ipsilateral fornix-stria-terminalis was observed in PDs with only pRBD compared to controls and to PDs without either comorbid disorder. Also, PDs with only pRBD manifested greater FA in contralateral putamen when compared to controls.

Conclusions: Our results suggest the presence of an underlying neural network in PDs with ICDs, particularly involving cerebellar connections, which makes the subjects susceptible to pRBD. Lower white-matter integrity in the fornix of PDs with only pRBD suggests a neuropathological pathway specific to sleep behavior disorder, independent of impulse control disorders. Greater white-matter integrity observed in PDs without comorbid ICDs, regardless of their comorbid pRBD status, might reflect compensatory mechanisms. Targeted therapies for this particular neuropathology may help prevent these comorbidities.