How Gender Roles Influence Alzheimer's Disease and Why Research is Needed

Women and men may develop Alzheimer's disease through different mechanisms. Understanding these differences is essential if the disease is to be treated effectively.

[This article has been originally published by Science Media Centre España.]

Alzheimer's disease is a disease of gender inequality. Women make up the majority of people with the disease and are also the majority of caregivers. Since age is the main risk factor, one might think that the greater longevity of women would explain the higher number of cases. However, the reality is much more complex: men and women are exposed to different risks, brain pathologies and levels of resistance to Alzheimer's disease.

In the vast majority of cases, this neurodegenerative disease is caused by a combination of genetic and environmental factors. This means that there is no single determining factor that explains its development. At a biological level, the disease is characterised by the deposition of amyloid and tau proteins inside and around neurons. Neurons are brain cells that act as 'messengers', receiving, processing and transmitting information to other neurons. In this way, they form a network that supports mental abilities such as memory. Amyloid and tau pathologies disrupt the functioning of these networks, leading to a progressive decline in mental abilities and eventually dementia.

Alzheimer's disease is a disease of gender inequality. Women make up the majority of people with the disease and are also the majority of caregivers

We now know that up to two decades can elapse between the onset of biological changes in the brain and the manifestation of mental dysfunction symptoms. This long period offers opportunities to influence the course of the disease. Previous studies have investigated how to slow the accumulation of amyloid and tau proteins to increase resistance to the pathology. Other studies have focused on understanding how to strengthen the ability of neurons to adapt to the accumulation of pathological proteins and maintain their function - a phenomenon known as disease resilience.

Resilience to the development of dementia

What can help increase resistance and resilience to diseases such as dementia? There are 12 recognised risk factors that increase the likelihood of developing dementia and may account for up to 40% of cases. These factors include education level, physical activity and depression. Improving these aspects can have a significant impact by providing the brain with greater protection and adaptability. But what is the role of sex and gender in disease resistance? The prevalence of protective and risk factors - and the burden of Alzheimer's disease - differs by sex and gender, reflecting biological and socially constructed factors.

Sex refers to a person's complement of sex chromosomes (XX vs. XY, female vs. male), which is reflected in the reproductive organs. In contrast, gender is a social construct that refers to socially constructed roles, identities and behaviours. Gender is complex and fluid, influenced by past and present social and cultural contexts. This binary approach (feminine/masculine, male/female) has limitations, but remains the most commonly used framework in research. 

What does research reveal about the role of sex and gender in resilience? A sex and gender perspective on Alzheimer's disease includes understanding that female sex may be associated with greater protein accumulation, while historical patterns of gender inequality may help explain the higher risk of Alzheimer's disease in women. 

A sex and gender perspective on Alzheimer's disease includes understanding that female sex may be associated with greater protein accumulation, while historical patterns of gender inequality may help explain the higher risk of Alzheimer's disease in women

Women initially cope better with the pathology and loss of neurons or neural connections, allowing them to maintain their mental abilities longer. Women are therefore more resilient to the early stages of the disease. For example, this greater initial resilience in women could be partly due to biological sex, since animal studies (where sex chromosomes can be manipulated in the laboratory) show a protective role for the X chromosome in Alzheimer's disease. However, as the disease progresses, women's mental abilities decline faster than men's. 

Thus, the initial resilience of women tends to fade as their mental abilities begin to deteriorate, leading to a diagnosis of Alzheimer's disease. Biological sex also seems to play an important role. During menopause (associated with female sex) there is greater accumulation of tau protein in the brain, and a greater presence of other brain pathologies (such as vascular pathologies) which contribute to greater neuronal damage. 

Assessing how sex and gender interact is crucial

It is important not to lose sight of how gender roles can influence disease risk. Some conditions that increase risk are more common in women, including low levels of education, physical inactivity and affective disorders inevitably related to caring. 

In an article published in Alzheimer's and Dementia: The Journal of the Alzheimer's Association, a group of researchers have highlighted the urgency of incorporating a sex and gender approach into studies of the pathology

Indeed, research suggests that, in countries with less gender inequality, the gap in mental ability between men and women is narrowing. Historically, women have been less encouraged to exercise and study, resulting in a higher prevalence of physical inactivity and lower educational attainment compared to men. Studies have shown that physical activity is associated with a lower accumulation of amyloid proteins in the brain. In addition, people with a higher level of education and those who engage in mental activities tend to have a larger volume of neurons in old age. Conversely, depression and stress can have a negative effect, reducing the number of neurons and possibly accelerating the accumulation of harmful proteins.

Assessing how sex and gender interact is crucial to understanding the mechanisms that preserve mental abilities, reduce the accumulation of pathology during ageing, and prevent Alzheimer's disease. Sex and gender are intertwined with other socially constructed concepts, such as race and ethnicity, which are essential for understanding and addressing inequalities in the development of disease. 

In the article published in Alzheimer's and Dementia: The Journal of the Alzheimer's Association, an international group of experts has highlighted the urgency of incorporating a sex and gender approach into Alzheimer's disease research. If women and men develop Alzheimer's disease through different mechanisms, understanding these mechanisms is essential to developing targeted interventions and effective treatments.