Vakili Kimia, Fathi Mobina, Ebrahimi Rasoul, Ahmadian Sarina, Moafi Maral, Ebrahimi Mohammad Javad, Tafazolimoghadam Armin, Davoodi Ali, Eghbaldoost Amirreza, Eyvani Kimia, Ghayyem Hani, Jashni Pour Mehraeen, Kosari Mohammadreza, Niknejad Sepideh, Sanaye Abbasi Ali, Zarebidoki Ameneh, Andrew Melissa, Trenaman Shanna, Batool Zehra, Sayehmiri Fatemeh, Ebrahimzadeh Kaveh
Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mol Neurobiol. 2025 Mar 20. doi: 10.1007/s12035-025-04821-9.
The gamma-aminobutyric acid (GABA) system is known for its role in cognitive functions and memory processes. However, the activity of GABA receptors and their associated pathways influence the accumulation of β-amyloid peptide (Aβ), a key hallmark in the development and prognosis of research examining the relationship between the use of drugs affecting GABA receptors and the risk of developing Alzheimer's disease (AD) and dementia. This study aimed to examine the association between GABAA receptor-affecting drugs and the risk of AD and dementia, focusing on benzodiazepines, zolpidem, and anesthetics. This meta-analysis included all English articles on AD, dementia, and GABA receptor agonist medications published before May 2024. The articles were identified through searches conducted on PubMed and Scopus databases. The extracted data were analyzed using STATA software (version 14.2). Q statistics and the I index were used to evaluate heterogeneity, while Egger's test and funnel plot were utilized to detect publication bias. A total of 19 articles (10 case-control and 9 cohort articles) were eligible for the analysis, involving 2,953,980 patients. The use of GABA agonists was found to have a statistically significant relationship with the development of dementia (RR = 1.15, 95% CI: 1.02-1.29, I = 87.6%) and AD (RR = 1.21, 95% CI: 1.04-1.40, I = 97.6%). In the drug-based subgroup, we observed that zolpidem consumption was associated with an increased incidence of AD and dementia (RR = 1.28, 95% CI: 1.08-1.52, I = 24.3%), similar to the effects of benzodiazepines (BZDs; RR = 1.11, 95% CI: 1.04-1.18, I = 87.2%). Meta-regression analysis showed that the duration of follow-up, which ranged from 5 to 11 years across the studies, was significantly associated with heterogeneity (P = 0.036). Our findings indicate that the use of zolpidem and BZD is associated with an increased risk of dementia and AD.
γ-氨基丁酸（GABA）系统因其在认知功能和记忆过程中的作用而闻名。然而，GABA受体的活性及其相关通路会影响β-淀粉样肽（Aβ）的积累，Aβ是研究影响GABA受体药物的使用与阿尔茨海默病（AD）和痴呆症发生风险之间关系的发展和预后的关键标志。本研究旨在探讨影响GABAA受体的药物与AD和痴呆症风险之间的关联，重点关注苯二氮䓬类药物、唑吡坦和麻醉剂。这项荟萃分析纳入了2024年5月之前发表的所有关于AD、痴呆症和GABA受体激动剂药物的英文文章。这些文章是通过在PubMed和Scopus数据库上进行检索而确定的。提取的数据使用STATA软件（版本14.2）进行分析。Q统计量和I指数用于评估异质性，而Egger检验和漏斗图用于检测发表偏倚。共有19篇文章（10篇病例对照研究和9篇队列研究文章）符合分析条件，涉及2953980名患者。发现使用GABA激动剂与痴呆症的发生有统计学显著关系（RR = 1.15，95%CI：1.02 - 1.29，I = 87.6%）和AD（RR = 1.21，95%CI：1.04 - 1.40，I = 97.6%）。在基于药物的亚组中，我们观察到服用唑吡坦与AD和痴呆症发病率增加有关（RR = 1.28，95%CI：1.08 - 1.52，I = 24.3%），类似于苯二氮䓬类药物（BZDs）的效果（RR = 1.11，95%CI：1.
