Cognitive effects of dopaminergic treatment in Alzheimer's disease: Systematic review and meta-analysis

IF 6.8 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-08-20 DOI:10.1002/trc2.70142

Cristina Bonet Olivares, Michael C. B. David, Marta Estrada Obeso, Martina Del Giovane, Suzanne Reeves, Paresh A. Malhotra

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引用次数: 0

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.

Abstract Image

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多巴胺能治疗阿尔茨海默病的认知效应：系统回顾和荟萃分析

尽管疾病改善药物取得了进展，但症状性阿尔茨海默病（AD）仍需要更好的治疗方法，多巴胺能神经传递是一个潜在的靶点。本系统综述和荟萃分析的目的是评估以多巴胺能为主的药物在改善AD患者认知症状方面的疗效。方法检索1980年至2023年1月的MEDLINE、Embase和ClinicalTrials.gov数据库。我们纳入了19项前瞻性随机对照阿尔茨海默病试验（1408名参与者），其中7项质量“好”，8项质量“一般”，4项质量“差”。所有人都被纳入了分析。总体综合效应较小，但与安慰剂相比，多巴胺能药物具有显著的积极作用（标准化平均差[SMD]: 0.33, 95%可信区间[CI]: 0.08 ~ 0.59, P = 0.01; I2 = 79%）。在去除异常值以解释异质性后，显著性仍然存在。在探索亚组（按作用机制划分）时，5项多巴胺再摄取抑制剂试验对认知没有显着影响，而12项单胺氧化酶B （MAO-B）抑制剂试验显示中度显著的积极作用（SMD: 0.52, 95% CI: 0.13 ~ 0.90, P = 0.01; I2 = 84%）。我们展示了多巴胺能药物，特别是MAO-B抑制剂，对AD患者认知症状的益处的证据。本文中包括的几项研究也使用了具有去甲肾上腺素能和多巴胺能作用的药物，强调了潜在的双重刺激可能导致更好的临床疗效。需要针对明确的患者群体进行试验，最好有多巴胺能功能障碍的生物标志物证据支持，比较去甲肾上腺素能和多巴胺能药物（单独或联合使用）对认知功能的影响，以最大限度地提高治疗效果。特别是，进一步的研究应该探索MAO-B药物对认知功能特定方面的影响，以更好地了解其在AD中MAO-B表达上调的机制。我们进行了一项荟萃分析，调查多巴胺能药物改善阿尔茨海默病（AD）认知症状的疗效。我们的研究结果强调了多巴胺能药物，特别是单胺氧化酶B抑制剂对AD的潜在认知益处。未来的试验是有必要的，可以集中在生物标志物定义的患者群体上，以提高有效性。

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.