Abstract
Alzheimers Dement (N Y). 2025 Aug 20;11(3):e70142. doi: 10.1002/trc2.70142. eCollection 2025 Jul-Sep.
ABSTRACT
INTRODUCTION: Despite advances in disease-modifying drugs, better treatments for symptomatic Alzheimer's disease (AD) are needed, with dopaminergic neurotransmission representing a potential target. The objective of this systematic review and meta-analysis was to evaluate the efficacy of drugs with predominantly dopaminergic action in improving cognitive symptoms in AD.
METHODS: The MEDLINE, Embase, and ClinicalTrials.gov databases were searched from 1980 to January 2023. We used random effect models to generate pooled effect estimates.
RESULTS: We included 19 prospective randomized controlled AD trials (1408 total participants), of which 7 were of "good" quality, 8 "fair," and 4 "poor." All were included in the analysis. The overall pooled effect was small but showed a significant positive effect of dopaminergic drugs compared to placebo (standardized mean difference [SMD]: 0.33, 95% confidence interval [CI]: 0.08 to 0.59, P = 0.01; I 2 = 79%). Significance remained after removing outliers to account for heterogeneity. When exploring subgroups (divided by mechanism of action), 5 trials of dopamine reuptake inhibitors did not show a significant effect on cognition, whereas 12 monoamine oxidase B (MAO-B) inhibitor trials showed a moderately significant positive effect (SMD: 0.52, 95% CI: 0.13 to 0.90, P = 0.01; I 2 = 84%).
DISCUSSION: We show evidence of the benefit of dopaminergic medications, specifically MAO-B inhibitors, on cognitive symptoms in AD. Several studies included here also used drugs with both noradrenergic and dopaminergic action, highlighting a potential dual stimulation that could lead to better clinical efficacy. Trials targeting well-defined patient populations, ideally supported by biomarker evidence of dopaminergic dysfunction, are needed to compare noradrenergic and dopaminergic agents-both separately and in combination-on cognitive function to maximize treatment effects. Particularly, further research should explore the impact of MAO-B drugs on specific aspects of cognitive function to better understand their mechanism given the upregulation of MAO-B expression in AD.
HIGHLIGHTS: We conducted a meta-analysis investigating the efficacy of dopaminergic drugs in improving cognitive symptoms in Alzheimer's disease (AD).Our findings highlight the potential cognitive benefits of dopaminergic medications, particularly monoamine oxidase B inhibitors, in AD.Future trials are warranted and could focus on biomarker-defined patient groups to enhance effectiveness.
PMID:40842491 | PMC:PMC12365664 | DOI:10.1002/trc2.70142