Sex and Gender Differences in Alzheimer's Disease - Chapter 9: Hormones and dementia

Elsevier, Sex and Gender Differences in Alzheimer's Disease, 2021, Pages 233-267
Cassandra Szoeke, Sue Downie, Susan Phillips, and Stephen Campbell

This chapter will focus on the sex hormone influence on cognition, cognitive decline, and the risk of dementia. We are only just beginning to look at the impact of reproductive aging on cognitive aging and a 2019 review showed how few aging studies have considered this (Taylor, Pritschet, Yu, & Jacobs, 2019), yet it is clearly an important question for at least two-thirds of those with dementia. There are strong indicators that the sex hormones have a role in cognition, neural activity, performance, brain structure, function, and inflammation. Given more than 100 years of dementia research has yielded no disease-modifying therapy or cure, it is clear our understanding of this complex neurodegenerative disease is incomplete. A snapshot of dementia research shows a predominance of research on older individuals (well after the onset of early changes in working memory circuitry (Jacobs et al., 2017)), often excluding those with vascular pathology (Ritchie, Terrera, & Quinn, 2015; Sperling et al., 2011) and there is an absence of reporting differences by sex, which then does not provide the opportunity to examine sex differences in results (Laws, Irvine, & Gale, 2016). Yet two-thirds of all dementia cases are women (Alzheimer Association, 2014), vascular risk and disease is a fundamental component of disease manifestation (de la Torre, 2010a; Harrison et al., 2014; Wiesmann, Kiliaan, & Claassen, 2013)—itself an area with well documented sex differences (Sobhani et al., 2018)—and it takes three decades for the neuropathological changes characteristic of Alzheimer’s dementia to reach levels clinically matched with a diagnosis (Villemagne et al., 2013). The menopausal transition occurs in the key window identified by dementia researchers as likely responsible for the chronic evolution of neurodegenerative processes from age 45 to manifestation of disease over 70 years.