Olivares, Cristina Bonet; David, Michael CB; Obeso, Marta Estrada; Del Giovane, Martina; Reeves, Suzanne; Malhotra, Paresh A; (2025) Cognitive effects of dopaminergic treatment in Alzheimer's disease: Systematic review and meta-analysis. Alzheimer's & Dementia , 11 (3) , Article e70142. 10.1002/trc2.70142.

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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; I² = 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; I² = 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.

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