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

Abstract

A BS TRACT: 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 (HTNÀ; n = 50) and patients with hypertension treated without DHP (HTN+/DHPÀ; 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 HTNÀ, HTN +/DHPÀ, and HTN+/DHP+ groups. The risks of levodopainduced 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+/DHPÀ (Bonferroni-corrected P log-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 longterm cognitive outcomes in hypertensive patients with PD.

Calcium channel blockers and Parkinson’s disease: a systematic review and meta-analysis

“…As shown in Table 2 , one study detected a protective role of CCB use on long-term cognitive outcomes of PD. 14 One study found an effect of CCB use on reducing the death risk of PD. 7 However, the other three studies failed to detect any impact of CCB use on the progression of PD.…”

“…We identified two studies reporting a positive effect of CCB use on the progression of PD. 7 , 14 Calcium interacts with α-synuclein and was a potential target for treating PD. 29 , 30 A study indicated that CCB could potentially prevent spine enlargement by inhibiting the hypersensitivity of the synapse to excitatory inputs in PD and, therefore, could be a candidate for treating levodopa-induced complications in PD.…”

“… 7 Another study found that using CCB was associated with better long-term cognitive performance in patients with PD. 14 However, a randomized trial failed to identify a significant treatment effect for the clinical progression of isradipine in patients with PD. 15 …”

The Role of Calcium and Iron Homeostasis in Parkinson’s Disease

“…The increased expression of Cav1.3 in the cerebral cortex of patients with early Parkinson's disease occurs before pathological changes, suggesting that calcium homeostasis disorders are not only a compensatory consequence of neurodegenerative processes [30], but also an early feature of Parkinson's disease. DHP antihypertensive drugs appear to be attractive agents for neuroprotective and preventive treatment of PD [31,32]. Epidemiological studies have shown that administration of DHP-type Ca 2+ channel blockers reduces the risk of PD in late life by 20 to 30% [33,34].…”