Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2013 Dec 2;47:167-71. doi: 10.1016/j.pnpbp.2012.06.007. Epub 2012 Jun 13.
Research has improved the diagnosis of Alzheimer's disease, and at earlier stages, but effective therapy continues to be elusive. Current effort is focused on delay. Environmental factors are thought to interact with genetics to modulate the progression of the disease, and one such environmental factor is exposure to general anesthetics. The possibility that some anesthetic effects have long-term consequences is of general interest and concern. The difficulty of studying a chronic, age-related disease in humans combined with the fact that anesthetics are rarely given without surgery, has led to a focus on animal models. Transgenic mouse models have been developed to mimic the hallmarks of Alzheimer's disease, including amyloid beta accumulation (plaque), neurofibrillary tangles, and cognitive dysfunction. While none of the models recapitulate the human disease with high fidelity, they allow a first look at anesthetic-Alzheimer interactions in a reasonable time frame. In studies found to date, none have concluded that anesthetics alone cause a significant change in cognitive decline, but rather an acceleration in Alzheimer neuropathology. Further studies are required to define the best anesthetic paradigm for our elderly population to mitigate changes in neuropathology and potentially cognition.
研究已经改善了阿尔茨海默病的诊断，并在更早的阶段，但有效的治疗方法仍然难以捉摸。目前的努力集中在延迟上。环境因素被认为与遗传因素相互作用，调节疾病的进展，而环境因素之一是暴露于全身麻醉剂。一些麻醉效果具有长期后果的可能性是人们普遍关注和关心的问题。由于难以在人类中研究慢性、与年龄相关的疾病，而且麻醉剂通常不是在没有手术的情况下使用，因此人们将注意力集中在动物模型上。已经开发出转基因小鼠模型来模拟阿尔茨海默病的特征，包括淀粉样β积累（斑块）、神经原纤维缠结和认知功能障碍。虽然没有一种模型能够高度逼真地再现人类疾病，但它们允许在合理的时间框架内首次观察麻醉与阿尔茨海默病的相互作用。迄今为止的研究发现，没有一项研究表明麻醉剂本身会导致认知能力下降的显著变化，而是加速了阿尔茨海默病的神经病理学变化。需要进一步的研究来确定最适合我们老年人群体的麻醉方案，以减轻神经病理学变化，并可能改善认知能力。
