Side of motor onset is associated with hemisphere-specific memory decline and lateralized gray matter loss in Parkinson's disease

• PDL performed worse on visuospatial memory tasks that are known to be mediated by the right hemisphere.
• PDL experienced lateralized GM loss that was localized predominantly in the right hemisphere.
• There were positive associations between lateralized memory decline and GM loss in PDL.

BackgroundParkinson's disease (PD) is a neurodegenerative disorder that generally begins with asymmetric motor symptoms that persist over time. This suggests that the dysfunction in the nigrostriatal motor circuit may be lateralized. The present study examined whether the asymmetric motor presentation is associated with hemisphere-specific cognitive decline and lateralized gray matter volume loss.MethodsData from comprehensive cognitive tests that measured visuospatial and verbal functions and high-resolution T1-weighted magnetic resonance images of the brain were acquired in 23 PD subjects with left-side motor symptom onset (PDL), 23 PD subjects with right-side onset (PDR), and 23 matched Controls. GM volume differences were assessed using voxel-based morphometry (VBM). Cognitive results and VBM were compared among the three groups, and correlation analyses were performed between those cognitive domains and brain areas that showed significant differences.ResultsPDL subjects had lower performance on visuospatial memory tasks compared to PDR. Furthermore, PDL subjects experienced lateralized GM loss, which was localized predominantly in the right hemisphere contralateral to the side of motor symptom onset. Visuospatial memory performance in PDL was correlated with GM loss in the right middle frontal gyrus and precuneus.ConclusionThese data suggest that the onset of asymmetric motor symptoms in PD may be associated with hemisphere-specific memory decline and lateralized GM loss, particularly in PDL. This study underscores the importance of classifying PD subgroups based on the side of motor symptom onset for clinical care and research to optimize cognitive outcomes.