Butler Tracy, Tey Sin-Ruow, Galvin James E, Perry George, Bowen Richard L, Atwood Craig S
Department of Radiology, Brain Health Imaging Institute, Weill Cornell Medicine, New York, NY, USA.
JangoBio, LLC, Division of Cell Biology, Fitchburg, WI, USA.
J Alzheimers Dis. 2024;101(3):705-713. doi: 10.3233/JAD-240334.
The increase in the incidence of dementia over the last century correlates strongly with the increases in post-reproductive lifespan during this time. As post-reproductive lifespan continues to increase it is likely that the incidence of dementia will also increase unless therapies are developed to prevent, slow or cure dementia. A growing body of evidence implicates age-related endocrine dyscrasia and the length of time that the brain is subjected to this endocrine dyscrasia, as a key causal event leading to the cognitive decline associated with aging and Alzheimer's disease (AD), the major form of dementia in our society. In particular, the elevations in circulating gonadotropins, resulting from the loss of gonadal sex hormone production with menopause and andropause, appear central to the development of AD neuropathology and cognitive decline. This is supported by numerous cell biology, preclinical animal, and epidemiological studies, as well as human clinical studies where suppression of circulating luteinizing hormone and/or follicle-stimulating hormone with either gonadotropin-releasing hormone analogues, or via physiological hormone replacement therapy, has been demonstrated to halt or significantly slow cognitive decline in those with AD. This review provides an overview of past and present studies demonstrating the importance of hypothalamic-pituitary-gonadal hormone balance for normal cognitive functioning, and how targeting age-related endocrine dyscrasia with hormone rebalancing strategies provides an alternative treatment route for those with AD.
在上个世纪，痴呆症发病率的增加与这段时期生殖后期寿命的延长密切相关。随着生殖后期寿命持续增加，痴呆症的发病率很可能也会上升，除非能开发出预防、延缓或治愈痴呆症的疗法。越来越多的证据表明，与年龄相关的内分泌失调以及大脑遭受这种内分泌失调的时间长度，是导致与衰老和阿尔茨海默病（AD，我们社会中痴呆症的主要形式）相关的认知衰退的关键因果事件。特别是，绝经和男性更年期导致性腺性激素分泌减少，从而使循环促性腺激素升高，这似乎是AD神经病理学发展和认知衰退的核心。这得到了众多细胞生物学、临床前动物和流行病学研究以及人体临床研究的支持，在这些研究中，使用促性腺激素释放激素类似物或通过生理性激素替代疗法抑制循环中的促黄体生成素和/或促卵泡生成素，已被证明可以阻止或显著减缓AD患者的认知衰退。本综述概述了过去和现在的研究，这些研究证明了下丘脑 - 垂体 - 性腺激素平衡对正常认知功能的重要性，以及如何通过激素再平衡策略针对与年龄相关的内分泌失调为AD患者提供一种替代治疗途径。
