Abstract

ObjectiveTo 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).MethodsAccording 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.ResultsPatients 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.InterpretationThe 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.

Highlights

  • Levodopa-induced dyskinesia (LID) occurs within several years in most patients with Parkinson’s disease (PD) who have undergone chronic dopamine replacement therapy,[1] the timing of the development of LID varies among patients

  • This study investigated the effects of baseline white matter hyperintensities (WMHs) burden on the development of LID in patients with drugna€ıve early stage PD

  • (1) patients with PD with moderate-to-severe WMHs were older and had higher UPDRS-III scores than those with minimal WMHs. (2) Patients in the PD group with moderate-to-severe WMHs had a higher risk of developing LID than those in the PD group with minimal WMHs, after adjustment for confounding factors such as age at onset, sex, striatal dopamine transporter (DAT) availability, and doses of PD medications

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Summary

Introduction

Levodopa-induced dyskinesia (LID) occurs within several years in most patients with Parkinson’s disease (PD) who have undergone chronic dopamine replacement therapy,[1] the timing of the development of LID varies among patients. WMH burden is associated with severe motor impairments, especially axial motor symptoms, in PD.[10,11,12]. These previous studies were essentially cross-sectional, and the effects of WMHs on long-term motor outcomes, including the development of LID, have not yet been reported. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

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