With disease-modifying treatments for Alzheimer's disease (AD) still elusive, the search for alternative intervention strategies has intensified. Growing evidence suggests that dysfunction in hypothalamic-pituitary-adrenal-axis (HPAA) activity may contribute to the development of AD pathology. The HPAA, may therefore offer a novel target for therapeutic action. This review summarises and critically evaluates animal and human studies investigating the effects of pharmacological and non-pharmacological intervention on HPAA modulation alongside cognitive performance. The interventions discussed include glucocorticoid receptor antagonists and 11β-hydroxysteroid dehydrogenase inhibitors as well as lifestyle treatments such as physical activity, diet, sleep and contemplative practices. Pharmacological HPAA modulators improve pathology and cognitive deficit in animal AD models, but human pharmacological trials are yet to provide definitive support for such benefits. Lifestyle interventions may offer promising strategies for HPAA modification and cognitive health, but several methodological caveats across these studies were identified. Directions for future research in AD studies are proposed.

中文翻译：

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下丘脑-垂体-肾上腺轴调节对阿尔茨海默病的治疗意义：药理学和生活方式干预的叙述性回顾

由于阿尔茨海默病 (AD) 的疾病缓解治疗仍然难以捉摸，因此寻找替代干预策略的工作已经加紧。越来越多的证据表明，下丘脑-垂体-肾上腺轴 (HPAA) 活动的功能障碍可能有助于 AD 病理的发展。因此，HPAA 可能为治疗作用提供新的靶点。本综述总结并批判性地评估了动物和人类研究，这些研究调查了药物和非药物干预对 HPAA 调节以及认知表现的影响。讨论的干预措施包括糖皮质激素受体拮抗剂和 11β-羟基类固醇脱氢酶抑制剂以及生活方式治疗，如体育活动、饮食、睡眠和冥想练习。药理学 HPAA 调节剂可改善 AD 动物模型的病理和认知缺陷，但人体药理学试验尚未为此类益处提供明确支持。生活方式干预可能为 HPAA 修改和认知健康提供有希望的策略，但在这些研究中发现了几个方法上的警告。提出了未来 AD 研究的方向。