Applying a Women’s Health Lens to the Study of the Aging Brain

Abstract

A major challenge in neuroscience is to understand what happens to a brain as it ages. Such insights could make it possible to distinguish between individuals who will undergo typical aging and those at risk for neurodegenerative disease. Over the last quarter century, thousands of human brain imaging studies have probed the neural basis of age-related cognitive decline. “Aging” studies generally enroll adults over the age of 65, a historical precedent rooted in the average age of retirement. A consequence of this research tradition is that it overlooks one of the most significant neuroendocrine changes in a woman’s life: the transition to menopause. The menopausal transition is marked by an overall decline in ovarian sex steroid production—up to 90% in the case of estradiol—a dramatic endocrine change that impacts multiple biological systems, including the brain. Despite sex differences in the risk for dementia, the influence that biological sex and sex hormones have on the aging brain is historically understudied, leaving a critical gap in our understanding of the aging process. In this Perspective article, we highlight the influence that endocrine factors have on the aging brain. We devote particular attention to the neural and cognitive changes that unfold in the middle decade of life, as a function of reproductive aging. We then consider emerging evidence from animal and human studies that other endocrine factors occurring earlier in life (e.g., pregnancy, hormonal birth control use) also shape the aging process. Applying a women’s health lens to the study of the aging brain will advance knowledge of the neuroendocrine basis of cognitive aging and ensure that men and women get the full benefit of our research efforts.

A history of previous childbirths is linked to women's white matter brain age in midlife and older age

“…Hence, the presented results may not apply to populations beyond those represented in this cohort. However, in context of the historical lack of research on women's brain health (Taylor, Pritschet, Yu, & Jacobs, 2019 ), the current results may prompt further study into how female‐specific factors such as pregnancy influences neural processes involved in normal ageing—as well as autoimmune conditions and Alzheimer's disease, of which the risks are higher for women relative to men (Natri, Garcia, Buetow, Trumble, & Wilson, 2019 ; Nichols et al, 2019 ).…”

A history of previous childbirths is linked to women’s white matter brain age in midlife and older age

“…Hence, the presented results may not apply to populations beyond those represented in this cohort. However, in context of the historical lack of research on women’s brain health [101], the current results represent a contribution that may prompt further study into how female biology influences neural processes involved in normal ageing - as well as autoimmune conditions and Alzheimer’s disease, of which the risks are higher for women relative to men [102, 103].…”

Towards an understanding of women's brain aging: the immunology of pregnancy and menopause

“…Despite the known sex differences in prevalence, as well as symptoms, severity, and treatment responses [25,26], there has been limited focus on how sex-specific immunology affects brain aging [27,25]. Recent studies have shown that pregnancy-related endocrinological fluctuations influence neural plasticity and brain structure in animals [28,29,30,31,32] and humans [33,34,35,36], and that biological processes related to menopause can have significant effects on brain health [37]. During pregnancy and menopause, the female immune system undergoes substantial changes [38,39], and evidence suggests that the immune regulations that occur during these major transitional phases may play an important part in women's brain aging trajectories [40,41,42].…”