Gray and white matter alterations in different predominant side and type of motor symptom in Parkinson's disease

BACKGROUND: Parkinson's disease (PD) is highly heterogeneous reflected by different affected side of body and type of motor symptom. We aim to explore clinical characteristics and underlying brain structure alterations in PD with different predominant sides and motor types. METHODS: We recruited 161 PD patients and 50 healthy controls (HC). Patients were classified into four subtypes according to their predominant side and motor type: left akinetic/rigid‐dominant (LAR), left tremor‐dominant (LTD), right akinetic/rigid‐dominant (RAR), and right tremor‐dominant (RTD). All participants assessed motor and cognitive performances, then underwent T1‐weighted and diffusion tensor imaging scanning. A general linear model was used to compare neuroimaging parameters among five groups. RESULTS: Among four PD subtypes, patients of LAR subtype experienced the worst motor impairment, and only this subtype showed worse cognitive performance compared with HC. Compared with HC and other subtypes, LAR subtype showed a significant reduction in cortical thickness of the right caudal‐anterior‐cingulate gyrus and fractional anisotropy of the right cingulum bundle. CONCLUSIONS: We demonstrated that LAR subtype had the worst clinical performance, which the severer damage in the right cingulate region might be the underlying mechanism. This study underscores the importance of classifying PD subtypes based on both the side and type of motor symptom for clinical intervention and research to optimize behavioral outcomes in the future.