White matter hyperintensities as a predictor of freezing of gait in Parkinson's disease

Introduction: To investigate the effect of white matter hyperintensities (WMH) on long-term motor outcomes in Parkinson's disease (PD). Methods: We retrospectively reviewed medical records of 268 patients with de novo PD (follow-up > 3 years). According to the Clinical Research Center for Dementia of South Korea (CREDOS) WMH visual rating scale scores, the patients were divided into two groups: a PD group with minimal WMH (PD-WMH-; n = 198) and a PD group with moderate to severe WMH (PD-WMH+; n = 70). We compared longitudinal increases in doses of dopaminergic medications between the two groups using a mixed model. We also assessed the effects of WMH on the development of freezing of gait (FOG). Results: Patients in the PD-WMH + group were older than those in the PD-WMH- group, and had more severe motor deficits and more severely decreased striatal dopamine transporter availability. The PD-WMH + group required higher doses of dopaminergic medications for symptom control, compared to the PD-WMH- group, over the follow-up period. After adjusting for age, sex, striatal dopamine transporter availability, and levodopa-equivalent dose, the PD-WMH + group showed a higher risk of developing FOG (HR, 3.29; 95% CI, 1.79–6.05; p < 0.001) than the PD-WMH- group. Conclusion: This study demonstrates that WMH burden negatively affects the longitudinal requirement of dopaminergic medication and the development of FOG. These findings suggest that baseline WMH severity or volume may be a useful prognostic marker of motor outcomes in PD.