Levodopa-induced dyskinesia is closely linked to progression of frontal dysfunction in PD

To assess the relationship between the development of levodopa-induced dyskinesia (LID) and longitudinal changes in cognition.

In this retrospective cohort study, we recruited 119 patients with Parkinson disease (PD) who underwent baseline and follow-up neuropsychological evaluations and were treated with levodopa for >5 years. On the basis of LID development, the patients were classified as patients with LID (PD-LID+, n = 38) or without LID (PD-LID-, n = 81) within 5 years of levodopa administration. After adjusting for age, sex, years of education, body mass index, motor severity at baseline, and levodopa increment per year, we compared the rates of cognitive decline using linear mixed model and dementia conversion using survival analysis between the groups.

Neuropsychological performances and the percentage of patients with mild cognitive impairment (MCI) at baseline did not differ between the groups. The PD-LID+ group showed faster declines in frontal executive function (p = 0.002) and global cognitive function. The conversion rate to dementia was significantly higher in the PD-LID+ group than in the PD-LID- group (adjusted hazard ratio [HR] 3.94, 95% confidence interval [CI] 1.76-8.82). Patients with MCI in the PD-LID+ group had a higher risk of PD dementia conversion than those with normal cognition (adjusted HR 6.08, 95% CI 1.25-29.56) or MCI (adjusted HR 4.05, 95% CI 1.14-14.43) in the PD-LID- group.

These results demonstrated that LID was closely associated with the progression of cognitive decline, especially frontal executive dysfunction, and the development of PD dementia.