勃起功能障碍药物与降低老年痴呆症风险有关

诸平

据英国伦敦大学学院(University College London简称UCL, Gower Street, London, UK) 2024年2月8日提供的消息，勃起功能障碍（Erectile Dysfunction简称ED）药物与降低老年痴呆症风险有关（Erectile dysfunction drugs linked to reduced Alzheimer’s risk）。

一项由伦敦大学学院(UCL)研究人员领导的新研究发现，通常用于治疗勃起功能障碍（ED）的药物可能会降低患阿尔茨海默病(Alzheimer’s disease)的风险。相关研究结果于2024年2月7日已经在美国神经病学学会（American Academy of Neurology）医学杂志《神经病学》（ Neurology）网站发表——Matthew Adesuyan, Yogini H. Jani, Dana Alsugeir, Robert Howard, Chengsheng Ju, Li Wei, Ruth Brauer. Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease. Neurology, 2024, 102 (4). DOI: 10.1212/WNL.0000000000209131. Published online: February 7, 2024. https://www.neurology.org/doi/10.1212/WNL.0000000000209131

根据此项研究，用于治疗ED的药物也可能与降低阿尔茨海默病的风险有关。但是该研究并没有证明治疗ED的药物能降低患阿尔茨海默病的风险，它只显示了一种关联。此论文的作者发现，服用ED药物的男性在几年后患阿尔茨海默病的可能性降低了18%。

这项研究包括近27万（实际上269725）名被诊断患有ED的男性，他们在研究开始时没有任何记忆或思维问题。超过一半(55%)的人服用磷酸二酯酶5型抑制剂药物（phosphodiesterase type 5 inhibitor drugs），包括西地那非(sildenafil)即商品名伟哥（Viagra）、他达拉非(tadalafil)商品名为西爱力(Cialis)、伐地那非（vardenafil）和阿瓦那非（avanafil），与那些没有服用这些药物的ED患者进行比较。ED药物通过扩张血管起作用，最初用于治疗高血压和心绞痛。它们作用于一种细胞信号信使，这种信使与记忆的联系也被研究过。这些药物也能穿过血脑屏障，并可能影响脑细胞的活动。动物研究发现磷酸二酯酶5型抑制剂具有一定的神经保护作用。 在上述研究中，基于处方记录，研究人员发现，在平均5.1年的随访时间里，研究人员根据潜在的混杂因素(如年龄、潜在的健康状况、联合处方药物和吸烟状况)调整了研究结果后发现，服用ED药物的男性后来患阿尔茨海默病的可能性降低了18%。这种关联在那些开过最多处方的男性中表现得最为明显，这表明更经常地使用这种药物可能对患阿尔茨海默病的风险有更大的影响。

在服用ED药物的男性中，749人患上了阿尔茨海默病，每万人-年（10000 person-years）中有8.1人患上了阿尔茨海默病。人-年代表参与研究的人数和每个人在研究中花费的时间。在没有服用药物的男性中，370人患上了阿尔茨海默病，相当于每万人-年9.7人患上了阿尔茨海默病。 该研究的主要作者、伦敦大学学院药学院（UCL School of Pharmacy）的露丝·布劳尔博士（Dr Ruth Brauer）说：“尽管我们在阿尔茨海默氏症的新疗法方面取得了进展，这些疗法可以清除大脑中的淀粉样斑块，帮助早期阿尔茨海默氏症患者，但我们迫切需要能够预防或延缓阿尔茨海默氏症发展的疗法。需要更多的研究来证实这些发现，更多地了解这些药物的潜在益处和作用机制，并研究最佳剂量。有必要对男性和女性参与者进行随机对照试验，以确定这些发现是否也适用于女性。”

第一作者、伦敦大学学院药学院的博士生马修·阿德苏扬(Matthew Adesuyan)说:“虽然我们不能根据我们的发现说药物本身是否降低了人们患阿尔茨海默病的风险，但结果是令人鼓舞的，可能指出了降低阿尔茨海默病风险的新方法。”

马修·阿德苏扬博士学位由伦敦大学学院医院(University College London Hospital简称UCLH) 英国国民健康保健制度（National Health Service简称NHS）基金会信托基金（NHS Foundation Trust）和伦敦大学学院药物优化研究与教育中心（Centre for Medicines Optimisation Research and Education）以及UCLH国家卫生研究所（UCLH National Institute for Health）和护理研究生物医学研究中心（Care Research Biomedical Research Centre）资助。

上述介绍，仅供参考。欲了解更多信息，敬请注意浏览原文或者相关报道。

Abstract

Background and Objectives

Repurposing phosphodiesterase type 5 inhibitors (PDE5Is) as drugs for Alzheimer disease (AD) risk reduction has shown promise based on animal studies. However, evidence in humans remains inconclusive. Therefore, we conducted a cohort study to evaluate the association between PDE5I initiation compared with nonuse and the risk of developing AD in men with erectile dysfunction (ED).

Methods

Using electronic health records from IQVIA Medical Research Data UK (formerly known as the THIN database), we identified men aged ≥40 years with a new diagnosis of ED between 2000 and 2017. Individuals with a previous diagnosis of dementia, cognitive impairment, confusion, or prescription for dementia symptoms were excluded. The occurrence of incident AD was identified using diagnostic read codes. To minimize immortal-time bias, PDE5I initiation was treated as a time-varying exposure variable. Potential confounders were adjusted using inverse probability of treatment weighting based on propensity scores. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) with 95% CIs. A secondary analysis explored the association between AD and the cumulative number of PDE5I prescriptions. Sensitivity analyses included lag (delay) periods of 1 and 3 years after cohort entry to address the prodromal stage of AD.

Results

The study included 269,725 men, with 1,119 newly diagnosed with AD during a median follow-up of 5.1 (interquartile range 2.9–8.9) years. The adjusted HR in PDE5I initiators compared with nonuse was 0.82 (95% CI 0.72–0.93). The associated risk of AD decreased in individuals issued >20 prescriptions: HR 0.56 (95% CI 0.43–0.73) for 21–50 prescriptions and HR 0.65 (95% CI 0.49–0.87) for >50 prescriptions. Sensitivity analysis with a 1-year lag period supported the primary findings (HR 0.82, 95% CI 0.72–0.94), but the results differed with the inclusion of a 3-year lag period (HR 0.93, 95% CI 0.80–1.08).

Discussion

PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions. The differences between primary and sensitivity analyses highlight the need to explore the optimal lag period. To enhance the generalizability of our findings, a randomized controlled trial including both sexes and exploring various PDE5I doses would be beneficial to confirm the association between PDE5I and AD.