National Centre for Sports and Exercise Medicine (NCSEM), School of Sports Exercise and Health Sciences (SSEHS), Loughborough University, Loughborough, UK.
Curr Top Behav Neurosci. 2023;62:309-331. doi: 10.1007/7854_2022_408.
BackgroundWomen in many cohorts have a higher risk for Alzheimer's disease (AD), the most common form of dementia. Sex is a biological construct whereby differences in disease manifestation and prevalence are rooted in genetic differences between XX and XY combinations of chromosomes. This chapter focuses specifically on sex-driven differences in dementia, as opposed to differences driven by gender - a social construct referring to the societal norms that influence people's roles, relationships, and positional power throughout their lifetime.MethodsUsing a narrative review, this chapter explored the characteristics and risk factors for the dementias, alongside a discussion of sex differences including loss of sex steroid hormones in middle-aged women, differences in the prevalence of cardiovascular diseases and engagement in lifestyle protective factors for dementia.ResultsThe sex difference in AD prevalence may exist because of systematic and historic differences in risk and protective factors for dementia, including level of education obtained and socioeconomic status differences, which can impact on health and dementia risk.Levels of sex steroids decline significantly after menopause in women, whereas this is more gradual in men with age. Animal and cell culture studies show strong biological plausibility for sex steroids to protect the ageing brain against dementia. Sex steroid hormone replacement therapy has in some observational studies shown to protect against AD, but treatment studies in humans have mainly shown disappointing results. Cardiovascular disease (CVD) shares midlife medical risk (e.g. hypertension, hyperlipidaemia, obesity etc.) factors with AD and other forms of dementia, but also with related lifestyle risk - and protective factors (e.g. exercise, not smoking etc.). Men tend to die earlier of CVD, so fewer survive to develop AD at an older age. Those who do survive may have healthier lifestyles and fewer risk factors for both CVD and AD. An earlier age at menopause also confers great risk for both without hormone treatment.DiscussionIt could be the case that the decline in sex steroids around the menopause make women more susceptible to lifestyle-related risk factors associated with dementia and CVD, but this remains to be further investigated. Combining hormone treatment with lifestyle changes in midlife (e.g. exercise) could be an important preventative treatment for dementia and CVD in later life, but this also requires further research.
在许多队列中，女性患阿尔茨海默病（AD）的风险更高，AD 是最常见的痴呆症形式。性别是一种生物学结构，疾病表现和患病率的差异源于 XX 和 XY 染色体组合的遗传差异。本章专门关注痴呆症中的性别驱动差异，而不是由性别驱动的差异 - 性别是一种社会结构，指的是影响人们在一生中角色、关系和地位权力的社会规范。
使用叙述性综述，本章探讨了痴呆症的特征和风险因素，以及性别差异，包括中年女性失去性激素、心血管疾病患病率差异以及参与保护痴呆症的生活方式因素。
AD 患病率的性别差异可能是由于痴呆症的风险和保护因素存在系统性和历史性差异，包括所获得的教育水平和社会经济地位差异，这些差异会影响健康和痴呆症风险。女性绝经后性激素水平显著下降，而男性随年龄增长逐渐下降。动物和细胞培养研究表明，性激素具有保护衰老大脑免受痴呆症侵害的强大生物学可能性。一些观察性研究表明，性激素激素替代疗法可以预防 AD，但人类治疗研究的结果主要令人失望。心血管疾病（CVD）与 AD 和其他形式的痴呆症具有中年医疗风险（如高血压、高脂血症、肥胖等）因素，但也与相关的生活方式风险和保护因素（如运动、不吸烟等）有关。男性往往因 CVD 更早死亡，因此，在老年时，没有 AD 发展的人更少。那些幸存下来的人可能有更健康的生活方式，CVD 和 AD 的风险因素也更少。绝经年龄较早也会极大地增加两者的风险，而没有激素治疗。
可能是绝经前后性激素水平下降使女性更容易受到与痴呆症和 CVD 相关的生活方式相关风险因素的影响，但这仍有待进一步研究。在中年时期将激素治疗与生活方式改变（例如运动）相结合，可能是预防晚年痴呆症和 CVD 的重要治疗方法，但这也需要进一步研究。
