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JAMA Intern Med:请注意!抗胆碱能药物可能导致阿尔兹海默症的到来

2019-06-28 佚名 生物探索

让人惊喜地是,最近发表在《JAMA Internal Medicine》的一篇论文报告了另一个可能的因素:抗胆碱能药物可能会导致阿尔兹海默症的患病风险明显增加。

众所周知,阿尔兹海默症(AD)在目前对我们来说是一个像迷一般的神经性退化疾病。随着病情的不断恶化,患者逐渐丧失身体机能,慢慢走向遗忘,走向死亡。

尽管我们不知道真正的病因,但却了解有些事情可能会成为阿尔兹海默症患病的诱因,比如说遗传、年纪、吸烟和饮酒等行为、或者与心脏病患病风险相一致的高胆固醇水平及血管中斑块的积聚等等。

让人惊喜地是,最近发表在《JAMA Internal Medicine》的一篇论文报告了另一个可能的因素:抗胆碱能药物可能会导致阿尔兹海默症的患病风险明显增加。

它所涉及的具体药物类型包括用于治疗抑郁症,肺部疾病和帕金森症的处方药,以及针对过敏症的非处方药,让人担心的是,这些药物在中老年人群体中备受欢迎。

乙酰胆碱假说再论证

这项研究由英国诺丁汉大学初级保健医学统计学教授Carol Coupland及其研究团队共同进行,他们选取来自英国1500多个医疗记录数据库中约285,000名55岁及以上志愿者信息,并对此进行了长达20年的随访。

他们意外地发现,其中近58000名被确诊患有阿尔兹海默症,并且服用抗胆碱能药物最多的人与从未服用这些药物的人相比,患阿尔兹海默症的可能性竟然高出约50%。



说到这里,大家肯定会疑问抗胆碱能药为什么会与阿尔兹海默症相关呢?

回顾阿尔兹海默症目前存在的假说,我们可以看到乙酰胆碱假说是最早提出的致病诱因假说。

乙酰胆碱作为一种参与众多神经系统功能的重要神经递质,对调节肌肉和控制信息传送到神经系统发挥至关重要的作用。若神经系统减少乙酰胆碱这一神经递质的产生,便会造成阿尔兹海默症的患病风险增加。

尽管之前许多研究也曾证实过长期服用抗胆碱能药物会存在记忆丧失或混乱的副作用。在这次研究中研究人员们进一步在抗胆碱能药物中发现了阻断乙酰胆碱的作用成分,同时研究结果也恰好为乙酰胆碱假说做出了大规模观察性试验的再论证。

为了进一步论证乙酰胆碱假说,研究人员们查看了此次研究中被诊断出患有阿尔兹海默症的患者的医疗记录,并检查了他们在被确诊前10年所服用的处方药情况,还将此情况与没有诊断出阿尔兹海默症的人进行对比。

对比之后发现,在随访的10年中,长达约3年每天服用强效抗胆碱能药物的人患阿尔兹海默症的风险比未曾服用过此类药物的人增加了约50%。同时,还发现抗胆碱能药物与80岁之前被诊断患有阿尔兹海默症的患者联系更为密切。

所有的抗胆碱能的药物都有此副作用吗?

该研究一共研究了56种抗胆碱能药物。但并不是每一种药物都与阿尔兹海默症的患病风险增加相关。仅仅一些抗抑郁药物,癫痫药和用于控制膀胱的药物与阿尔兹海默症风险增加联系较为密切。



相关性药物:

抗抑郁药:阿米替林,帕罗西汀,去甲替林和多虑平

抗癫痫药:卡马西平和奥卡西平

抗精神病药:喹硫平,奥氮平,氯丙嗪和奋乃静

帕金森病的药物:苯那嗪,奥芬那林和苯海索

用于膀胱控制的药物:达利那新,非索罗定,奥昔布宁和托特罗定

无相关性药物:

抗组胺药:苯海拉明和羟嗪

肠动物解痉药:双环胺和hyoscinepropantheline

异丙肾上腺素支气管扩张剂:异丙托溴铵

抗心律失常药:丙吡胺

骨骼肌松弛剂:替扎尼定和methocarbamol

未来还需更完整的解释

虽然这样的研究结果很有趣,但许多科学家并不认为药物治疗是患病的明确危险因素。

首先,该研究旨在检测药物与阿尔兹海默症之间的联系,而不是因果关系。

其次,正如阿尔兹海默症协会科学计划和外展主任Keith Fargo所评价道的那样,“这是一项非常大的研究,似乎设计得很好,但这种研究的问题是无论你如何设计它,它都是不可能完全控制所有可能的混淆变量。

无法完全忽视的是患者在服用这类药物时,其实在很大程度上已经出现了与阿尔兹海默症相关的高度潜在风险,而不是药的原因。

Keith Fargo对于这一研究成果能否改变目前的临床守则,同样不太看好。他认为这一结果目前不太可能改变医生开出处方药的方式,至少需要更多研究以澄清这类药物究竟是如何影响阿尔兹海默症患病的风险。

原始出处:
Carol A. C. Coupland, et al. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. Jun 2019.

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    2023-08-09 ms9000001657969304 来自山西省

    谢谢分享

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    2019-06-30 grace5704
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    2019-06-29 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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    2019-06-28 orangesking

    0

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