Almutairi Jawza A, Kidd Emma J
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
Department of Pharmaceutical Science, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
Curr Top Behav Neurosci. 2025;69:79-104. doi: 10.1007/7854_2024_545.
Alzheimer's disease is a highly complex and multifactorial neurodegenerative disorder, with age being the most significant risk factor. The incidence of Alzheimer's disease doubles every 5 years after the age of 65. Consequently, one of the major challenges in Alzheimer's disease research is understanding how the brain changes with age. Gaining insights into these changes could help identify individuals who are more prone to developing Alzheimer's disease as they age. Over the past 25 years, studies on brain aging have examined thousands of human brains to explore the neuronal basis of age-related cognitive decline. However, most of these studies have focused on adults over 60, often neglecting the critical menopause transition period. During menopause, women experience a substantial decline in ovarian sex hormone production, with a decrease of about 90% in estrogen levels. Estrogen is known for its neuroprotective effects, and its significant loss during menopause affects various biological systems, including the brain. Importantly, despite known differences in dementia risk between sexes, the impact of biological sex and sex hormones on brain aging and the development of Alzheimer's disease remains underexplored.
阿尔茨海默病是一种高度复杂且多因素的神经退行性疾病，年龄是最重要的风险因素。65岁之后，阿尔茨海默病的发病率每5年就会翻一番。因此，阿尔茨海默病研究中的一大主要挑战是了解大脑如何随年龄变化。深入了解这些变化有助于识别出随着年龄增长更易患阿尔茨海默病的个体。在过去25年里，关于大脑衰老的研究已经检查了数千个人脑，以探索与年龄相关的认知衰退的神经元基础。然而，这些研究大多集中在60岁以上的成年人，常常忽略了关键的绝经过渡期。在绝经期间，女性的卵巢性激素分泌大幅下降，雌激素水平降低约90%。雌激素以其神经保护作用而闻名，绝经期间雌激素的显著减少会影响包括大脑在内的各种生物系统。重要的是，尽管已知男女在痴呆风险方面存在差异，但生物性别和性激素对大脑衰老及阿尔茨海默病发展的影响仍未得到充分研究。
