Sex Differences in Dementia.

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.