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

Mov Disord. 2023 May;38(5):843-853. doi: 10.1002/mds.29367. Epub 2023 Feb 24.

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.

Keywords: Parkinson's disease; calcium channel blocker; dementia; dihydropyridine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiparkinson Agents / adverse effects
  • Cognition
  • Dihydropyridines* / therapeutic use
  • Dopamine Plasma Membrane Transport Proteins
  • Dyskinesias* / drug therapy
  • Humans
  • Hypertension* / drug therapy
  • Levodopa / adverse effects
  • Parkinson Disease* / complications
  • Parkinson Disease* / drug therapy

Substances

  • Levodopa
  • Antiparkinson Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Dihydropyridines