Cognitive Decline, Dementia Associated With Levodopa-Induced Dyskinesia in PD

The fiber tracts involved in aging. The splenium and genu of the corpus callosum, the fornix and the cingulum bundle. Human subject

The development of levodopa-induced dyskinesia (LID) appears to correlate with cognitive decline, as well as with the development of Parkinson disease (PD) dementia, researchers found. The findings from this study were published in Neurology.

A total of 119 patients with PD who were treated with levodopa for more than 5 years were included in this retrospective cohort study. All patients had undergone baseline and follow-up neuropsychological and brain MRI and N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography examinations. Patients were classified either as having LID (PD-LID+; n=38) or not having LID (PD-LID-; n=81). In an analysis adjusted for age, sex, years of education, body mass index, motor severity at baseline, and levodopa increment per year, the investigators compared the cognitive decline rates using a linear mixed model and dementia conversion between the PD-LID+ and PD-LID- groups.

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There was no difference between the 2 groups at baseline with regard to neuropsychological performance or the proportion of patients with mild cognitive impairment. Patients in the PD-LID+ group had significantly faster frontal executive function declines compared with the PD-LID- group (-0.149; P =.002). Additionally, the PD-LID+ group had significantly faster declines in global cognitive function (-0.090; P =.033) and total Mini-Mental State Examination score (-0.351; P =.012).

In addition, patients in the PD-LID+ group had a higher conversion rate to dementia compared with those in the PD-LID- group (adjusted hazard ratio [aHR], 3.94; 95% CI, 1.76–8.82; P =.010). The PD-LID+ group also demonstrated a higher PD dementia conversion risk if they had mild cognitive impairment, compared with those in the PD-LID- group with normal cognition (aHR, 6.08; 95% CI, 1.25–29.56) or mild cognitive impairment (aHR 4.05; 95% CI, 1.14–14.43).

Limitations of the study include the high exclusion rate as well as the retrospective nature of the analysis.

Findings from this study “provide us with a new perspective in the investigation of the pathophysiology of LID and cognitive decline in PD and the contributions of chronic dopaminergic stimulation to plasticity to cognition,” the researchers concluded.


Yoo HS, Chung SJ, Lee YH, et al. Levodopa-induced dyskinesia is closely linked to progression of frontal dysfunction in PD [published online February 22, 2019]. Neurology. doi:10.1212/WNL.0000000000007189.