Jett Steven, Schelbaum Eva, Jang Grace, Boneu Yepez Camila, Dyke Jonathan P, Pahlajani Silky, Diaz Brinton Roberta, Mosconi Lisa
Department of Neurology, Weill Cornell Medical College, New York, NY, United States.
Department of Radiology, Weill Cornell Medical College, New York, NY, United States.
Front Aging Neurosci. 2022 Jul 19;14:948219. doi: 10.3389/fnagi.2022.948219. eCollection 2022.
Ovarian hormones, particularly 17β-estradiol, are involved in numerous neurophysiological and neurochemical processes, including those subserving cognitive function. Estradiol plays a key role in the neurobiology of aging, in part due to extensive interconnectivity of the neural and endocrine system. This aspect of aging is fundamental for women's brains as all women experience a drop in circulating estradiol levels in midlife, after menopause. Given the importance of estradiol for brain function, it is not surprising that up to 80% of peri-menopausal and post-menopausal women report neurological symptoms including changes in thermoregulation (vasomotor symptoms), mood, sleep, and cognitive performance. Preclinical evidence for neuroprotective effects of 17β-estradiol also indicate associations between menopause, cognitive aging, and Alzheimer's disease (AD), the most common cause of dementia affecting nearly twice more women than men. Brain imaging studies demonstrated that middle-aged women exhibit increased indicators of AD endophenotype as compared to men of the same age, with onset in perimenopause. Herein, we take a translational approach to illustrate the contribution of ovarian hormones in maintaining cognition in women, with evidence implicating menopause-related declines in 17β-estradiol in cognitive aging and AD risk. We will review research focused on the role of endogenous and exogenous estrogen exposure as a key underlying mechanism to neuropathological aging in women, with a focus on whether brain structure, function and neurochemistry respond to hormone treatment. While still in development, this research area offers a new sex-based perspective on brain aging and risk of AD, while also highlighting an urgent need for better integration between neurology, psychiatry, and women's health practices.
卵巢激素，尤其是17β-雌二醇，参与众多神经生理和神经化学过程，包括那些与认知功能相关的过程。雌二醇在衰老的神经生物学中起关键作用，部分原因是神经和内分泌系统之间广泛的相互联系。衰老的这一方面对女性大脑至关重要，因为所有女性在中年绝经后循环雌二醇水平都会下降。鉴于雌二醇对脑功能的重要性，高达80%的围绝经期和绝经后女性报告有神经症状，包括体温调节变化（血管舒缩症状）、情绪、睡眠和认知表现的改变，这并不奇怪。17β-雌二醇神经保护作用的临床前证据也表明绝经、认知衰老和阿尔茨海默病（AD）之间存在关联，AD是痴呆最常见的病因，影响女性的人数几乎是男性的两倍。脑成像研究表明，与同龄男性相比，中年女性在围绝经期开始出现AD内表型指标增加。在此，我们采用转化医学方法来说明卵巢激素在维持女性认知方面的作用，有证据表明绝经相关的17β-雌二醇下降与认知衰老和AD风险有关。我们将回顾聚焦于内源性和外源性雌激素暴露作为女性神经病理性衰老关键潜在机制作用的研究，重点关注脑结构、功能和神经化学是否对激素治疗有反应。虽然该研究领域仍在发展中，但它为脑衰老和AD风险提供了一个基于性别的新视角，同时也凸显了神经病学、精神病学和女性健康实践之间更好整合的迫切需求。
