One in three people globally live with a brain disease and the total number of people who have died as a result has increased significantly over the past 30 years, costing US$1.7trn in the US and Europe [1].

Women are at the epicentre of this emerging crisis.They are twice as likely to have major depressive disorder as men—representing more than two-thirds of patients with Alzheimer's disease [2]—and are nearly twice as likely as men to suffer from mental illness [3]. However, there is not enough understanding about sex and gender-specific differences between the prevalence and incidence of neurological conditions. For example, although stroke incidence is decreasing over time, this is driven by decreases in ischemic stroke in men. The reasons behind this difference in incidence between men and women remains unknown [4].

Health outcomes for neurological diseases also vary in alignment with the socio-cultural determinants of health

There is increasing evidence demonstrating a widening sex- and gender-based gap in outcomes for brain health disorders, with strikingly negative outcomes for women [5]. Differences in prevalence, diagnosis and treatment are especially common when it comes to brain health in women. For example, of the nearly 7m people in the US with Alzheimer’s, 66% are women [6]. On a global scale, Multiple Sclerosis, an autoimmune disease, is twice as common in women [3].

Social determinants like sex and gender have an impact not only on disease burden but across all stages of brain disease and disease trajectory. Sex (denoted by characteristics that are biologically defined) and gender (denoted by socially constructed features) influence the level of access to neurological care, the speed of diagnosis and treatment and the patient’s response to treatment. These factors also modulate the biology of disease, both directly and indirectly, through their influences on lifestyle risk factors and comorbidities.

The growing burden of brain disorders will economically impact individuals, families and society

The economic costs of brain diseases are extensive. Beyond the clinical costs of care, symptoms can make maintaining a job difficult and lead to patients leaving the workforce, and can cause poorer educational outcomes for younger patients . Similar trends are also seen amongst caregivers. High caregiving demands occur during early midlife, when women are often most professionally and economically successful. In 2018, women accounted for two-thirds of dementia caregivers, providing 18.5bn unpaid hours of care—equivalent to approximately $234bn [2]. Tackling brain diseases equitably is therefore not just a health problem, but also an economic one.

Women are underrepresented in research, a key component of any efforts to shrink these inequality in outcomes

Despite the clear disproportionate physical, social and economic burden of many brain diseases in women, research remains dominated by male representation. For example only 12% of 2019  Alzheimer’s funding from the National Institutes of Health was allocated to projects focused on women [7]. Although evidence suggests that the adult human brain is not uniformly male-typical or female-typical, there are regions of the brain that have clear sex-based differences [8][9]. Therefore, representative research is required to better understand the role of sex and gender in brain disease. The Women’s Health Access Matters report found that doubling the funds for women’s Alzheimer’s research would pay for itself three times over. The report also found that this 224% return on investment would add 15% more to the global economy than general Alzheimer’s research. Investing US$300m into research focused on Alzheimer’s in women would generate $930m in economic gains, add 4,000 years of life, eliminate 6,500 cases of the disease and related dementias, and save 3,500 years of nursing home care and costs [10].

For this reason, over the past eight months Economist Impact, has been exploring the role of sex and gender in brain disease outcomes. We have been building the economic case for greater investment in sex- and gender-inclusive brain research through a programme commissioned by the Women's Brain Project. In March, our findings will be released in a whitepaper. This will focus on the economic manifestation across five brain diseases: Multiple sclerosis, stroke, Parkinson’s disease, Alzheimer’s disease and migraine.

We developed five conceptual frameworks, which convey how greater investments in sex- and gender-specific research would affect national GDP for each of the brain diseases examined. The frameworks define how research-driven improvements in clinical guidelines, drug development and efficacy would change the course of the diseases through better clinical management—reducing disease severity and mortality and ultimately increasing productivity.

The main conclusions of our work identify levers that can shift the needle in neurological disease outcomes for women. These include:

• Designing clinical trial recruitment methodologies that encourage broader participation and prioritise representation of those most affected.

• Establishing closer relationships between funding and sex- and gender-informed research design and participation.

• Raising awareness and sensitising healthcare professionals around sex- and gender-driven differences and presentations in disease, from symptoms through to progression and management. 

• Recognising the ways in which implicit biases may influence clinical decision making and outcomes. 

• Increased funding to drive momentum in explorative research to broaden current understandings of sex- and gender-based differences in brain disease research.

Addressing inequalities in clinical research and creating representative solutions will support equitable and more effective service provision, and a better prognosis for brain diseases for all.

[1] Feigin V. The Evolution of neuroepidemiology: Marking the 40-Year anniversary of publishing studies on epidemiology of neurological disorders. Neuroepidemiology. 2022;56(1):2-3.
[2] Goldstein JM, Langer A and Lesser JA. Sex differences in disorders of the brain and heart - A global crisis of multimorbidity and novel opportunity. JAMA Psychiatry. 2021;78(1):7-8. doi:10.1001/jamapsychiatry.2020.1944
[3] Yu S. Uncovering the hidden impacts of inequality on mental health: A global study. Transl Psychiatry. 2018;8(1):98. doi:10.1038/s41398-018-0148-0
[4] Madsen TE, Khoury J, Alwell K et al. Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study. Neurology. 2017; 89(10):990-996. doi: 10.1212/WNL.0000000000004325
[5] Smith E, Kawaguchi N, Chapman SB et al. August 2021. Closing the brain health gap: Addressing women’s inequalities. OUPblog. [https://blog.oup.com/2021/08/closing-the-brain-health-gap-addressing-womens-inequalities/]. Accessed March 2023.
[6] Alzheimer's Association. Alzheimer's disease facts and figures. [https://www.alz.org/alzheimers-dementia/facts-figures]. Accessed March 2023.
[7] WHAM. April 2021. Investing in women’s Alzheimer’s research yields greater economic returns, study finds. Women’s Health Access Matters; Greenwich, CT. [https://thewhamreport.org/investing-in-womens-alzheimers-research-yields-greater-economic-returns-study-finds/]. Accessed March 2023.
[8] Goldman B. May 2017. Two minds: The cognitive differences between men and women. Stanford Medicine Magazine: Stanford, CA. [https://stanmed.stanford.edu/how-mens-and-womens-brains-are-different/]. Accessed March 2023
[9] Hines M. Neuroscience and sex/gender: Looking back and forward. J Neurosci. 2020;40(1):37-43. doi:10.1523/JNEUROSCI.0750-19.2019
[10] WHAM. The WHAM report. Women’s Health Access Matters; Greenwich, CT. [https://thewhamreport.org/]. Accessed March 2023.