In CRBLM Research Spotlight articles, we provide accessible summaries to highlight current and ongoing work being produced by our members on various themes. “Research-Policy Connections” posts each focus on a single published article, giving a very short summary and highlighting potential applications to real-world policy matters.

Blog post by Mehrgol Tiv

Reference article: Subramaniapillai, S., Rajagopal, S., Snytte, J., Otto, R., Einstein, G. and M. N. Rajah. (2021). Sex differences in brain aging among adults with APOE4 genetic risk and family history of Alzheimer’s Disease. Neuroimage: Clinical.

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According to the Alzheimer’s Association, one in nine people aged 65 years and older has Alzheimer’s dementia. What factors predict whether someone is likely to get Alzheimer’s in older age? Researchers at McGill University, the Douglas Institute Research Centre, University of Toronto, Rotman Research Institute, Linköping University, and the Center for Research on Brain, Language, and Music found that among people with a certain gene form and family history of Alzheimer’s, women may be more at risk than men with similar profiles.

Alzheimer’s is a brain disease of worsening memory and thinking that disrupts daily life. For many, this disease can also bring social and economic challenges. However, some people are more at risk for developing Alzheimer’s than others. For instance, women make up two thirds of individuals with Alzheimer’s. Similarly, some peoples’ brains naturally age faster than other peoples’ brains. This means that a 40-year-old person can have a brain that is more similar to an average 30-year-old’s brain (a younger brain) or more similar to an average 50-year-old’s brain (an older brain). Older brain individuals have a higher risk of developing Alzheimer’s disease, as do people with a specific form of a gene (APOE) and those with a history of Alzheimer’s in the family. While these risks (sex and/or gender, gene form, family history) are non-modifiable, there are also risk factors for Alzheimer’s disease that can be modified, including Body Mass Index (BMI), blood pressure, and physical activity. While importantly, none of these risks, non-modifiable nor modifiable, means the person will definitely develop Alzheimer’s disease, it is not clear how these factors interact to put some people at more risk than others.

This paper reveals that non-modifiable risk factors (gene form) and modifiable ones (BMI and physical activity) manifest differently in women and men who already have a family history of Alzheimer’s disease. Women with these biological risk factors have older appearing brains than men, which could mean that these women experience a higher chance of developing Alzheimer’s in the future. Moreover, among individuals with greater Alzheimer’s risk, factors that preserve body weight (high BMI, low exercise) could have different effects for women and men. For instance, high BMI may be somewhat protective for women at risk for Alzheimer’s, and this may be because of what happens with the hormone estrogen after women experience menopause in older age. Among post-menopausal people, the primary source of estrogen shifts from the ovaries to fatty tissues and losing this fat may decrease the total amount of estrogen in their bodies to fight against brain disease, like Alzheimer’s.

This research highlights several key policy implications related to Alzheimer’s disease. First, more research funding is needed to support studies that examine Alzheimer’s risk factors for different sexes and genders, which includes individuals who changed from their biological sex, as well as the different sex- and gender-based sociocultural practices, roles, and expectations. For instance, the authors point out that in families with a history of Alzheimer’s, women are often expected to provide familial care, and this added stress may put them at greater risk for developing Alzheimer’s themselves. This perspective can inform Canada’s 2019 National Dementia Strategy, which is currently developing its action plan, to centralize research on potential demographic differences. A second policy implication extends beyond research and involves detection, preventative care, and early treatment. As this study has shown, accounting for a variety of risk factors can lead to a more nuanced assessment of which individuals are more or less likely to develop Alzheimer’s disease. This type of information, if integrated in public health policies and programs, may relieve some financial and capacity burdens on medical specialists and the public health system, allowing more people to have access to care and treatment earlier on.

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