Watermeyer Tamlyn, Robb Catherine, Gregory Sarah, Udeh-Momoh Chinedu
Department of Psychology, Faculty of Health and Life Sciences, Northumbria University, Newcastle, UK; Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Ageing Epidemiology Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London, UK.
Front Neuroendocrinol. 2021 Jan;60:100877. doi: 10.1016/j.yfrne.2020.100877. Epub 2020 Oct 9.
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-pituitaryadrenal-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.
由于治疗阿尔茨海默病（AD）的疾病修饰疗法仍未找到，寻找替代干预策略的工作已日益加强。越来越多的证据表明，下丘脑-垂体-肾上腺轴（HPAA）活动功能失调可能促使AD病理发展。因此，HPAA可能提供一个新的治疗作用靶点。本综述总结并批判性评估了研究药物和非药物干预对HPAA调节以及认知表现影响的动物和人体研究。所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，以及诸如体育活动、饮食、睡眠和冥想练习等生活方式治疗。药物性HPAA调节剂可改善动物AD模型中的病理状况和认知缺陷，但人体药物试验尚未为此类益处提供确凿支持。生活方式干预可能为HPAA调节和认知健康提供有前景的策略，但这些研究中存在若干方法学上的问题。本文还提出了AD研究未来的研究方向。
