Effects of Dihydropyridines on the Motor and Cognitive Outcomes of Patients with Parkinson's Disease

ABSTRACT Background Dihydropyridines (DHPs) may have neuroprotective effects against Parkinson's disease (PD). Objective This study investigated the effects of DHPs on nigrostriatal dopaminergic denervation and longitudinal motor and cognitive outcomes in PD. Methods We classified 476 patients with drug‐naive PD who had undergone dopamine transporter imaging into three groups. They were selected according to a prior diagnosis of hypertension and use of DHPs and were matched using propensity scores: patients without hypertension (HTN−; n = 50) and patients with hypertension treated without DHP (HTN+/DHP−; n = 50) or with DHP (HTN+/DHP+; n = 50). Multiple linear regression and linear mixed model analyses were performed to determine intergroup differences in baseline dopamine transporter availability and longitudinal changes in the levodopa‐equivalent dose, respectively. Using Kaplan–Meier analyses, we compared the risks of levodopa‐induced dyskinesia, wearing off, and dementia‐free survival during the 5.06 years of the mean follow‐up period. The Cox regression model determined the independent effects of DHPs on dementia conversion. Results Dopamine transporter availability in all striatal subregions was comparable between the HTN−, HTN+/DHP−, and HTN+/DHP+ groups. The risks of levodopa‐induced dyskinesia and wearing off, as well as longitudinal changes in the levodopa‐equivalent dose, did not differ between the groups. The HTN+/DHP+ group had a lower risk of developing dementia than the HTN+/DHP− (Bonferroni‐corrected Plog‐rank = 0.036) group. The use of DHP was independently associated with a lower risk of dementia conversion after controlling for other antihypertensive drugs and confounding factors (hazard ratio, 0.242; 95% confidence interval, 0.087–0.668; P = 0.006). Conclusions DHPs may be associated with better long‐term cognitive outcomes in hypertensive patients with PD. © 2023 International Parkinson and Movement Disorder Society.