Abstract
Introduction: Primary outcome of this study is to elucidate the predictive role of subtle motor impairment evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III on mortality and functional outcome. Secondary outcome is to evaluate the association of motor impairment with small vessel disease (SVD) severity. Methods: We derived data from a Japanese cohort of patients with evidence of SVD who were enrolled from 2015 to 2019, and followed until 2023. The present study included 586 participants who agreed for UPDRS Part III evaluation. The severity of white matter hyperintensities (WMH) and the presence of lacunes were evaluated. Cox proportional hazard models and multiple logistic regression analysis were used to examine the association between UPDRS Part III score, and all-cause death and functional outcome defined by the modified Rankin Scale (mRS) score at last visit, respectively. Results: The median age was 71 years, and the median UPDRS Part III score was 2. The UPDRS Part III score was associated with the severity of WMH (r=0.225, P<0.001) and the number (0, 1, >2) of lacunes (P<0.001). During a mean follow-up period of 4.8 years, 29 patients died. The Cox proportional hazard analysis revealed that high UPDRS Part III scores (>5) were associated with higher risk of all-cause death compared to low (score 0) and middle (score 1-4) scores (adjusted hazard ratio 3.04; 95% confidence interval, 1.50-7.34, P=0.005). In multivariate logistic analysis, high UPDRS Part III scores were associated with poor functional outcome (mRS of 3 or more) compared with low and middle scores after adjusting for confounding factors (adjusted odds ratio 1.86; 95% confidence interval 1.02-3.41, P=0.043). Conclusions: Subtle motor impairment was associated with the severity of WMH and numbers of lacunes, and could predict mortality and poor functional outcome independently of vascular risk factors and severity of WMH and lacunes.