White matter hyperintensities and risk of levodopa-induced dyskinesia in Parkinson’s disease

Objective: To investigate whether the burden of white matter hyperintensities (WMHs) is associated with the risk of developing levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). Methods: According to the Clinical Research Center for Dementia of South Korea WMH visual rating scale, 336 patients with drug-naïve early stage PD (follow-up >3 years) were divided into two groups of PD with minimal WMHs (PD-WMH–; n = 227) and moderate-to-severe WMHs (PD-WMH+; n = 109). The Cox regression model was used to estimate the hazard ratio for the development of LID in the PD-WMH + group compared with the PD-WMH– group, while adjusting for age at PD onset, sex, striatal dopamine depletion, and PD medication dose. Additionally, we assessed the effects of WMH burden rated by the Scheltens scale and regional WMH distribution on the development of LID. Results: Patients in the PD-WMH + group were older and had more severe parkinsonian motor signs despite comparable striatal dopamine transporter availability than those in the PD-WMH– group. Patients in the PD-WMH + group had a higher risk of developing LID (hazard ratio, 2.66; P < 0.001) than those in the PD-WMH– group after adjustment for other confounding factors. A greater WMH burden was associated with earlier occurrence of LID (hazard ratio, 1.04; P = 0.001), although the effects of WMHs on LID development did not exhibit region-specific patterns. Interpretation: The present study demonstrates that the burden of WMHs is associated with occurrence of LID in patients with PD, suggesting comorbid WMHs as a risk factor for LID.