Understanding the Gender Gap in Alzheimer's Disease
Women are twice as likely as men to be diagnosed with Alzheimer's disease.
Posted November 17, 2025 | Reviewed by Jessica Schrader
Over 7 million people in the United States are living with Alzheimer’s disease. Unfortunately, this number is expected to double by 2050. Women outnumber their male counterparts by almost a two-to-one margin. Although in general, women tend to live longer than men, aging alone cannot account for the differences in the number of women who are disproportionately represented. What factors account for the sex difference?
Women have two X chromosomes, whereas men have one X and one Y chromosome. Just because women have two X chromosomes does not mean they have twice as much genetic material, because one of the female X chromosomes is silent. In addition, the APOE gene, which is the strongest genetic risk factor for late-onset Alzheimer’s, is more pronounced in females.
Genes on the X chromosome are related to immune function, brain function, and Alzheimer’s disease. Inflammation has been linked to many chronic diseases, including neurodegenerative ones like Parkinson’s and multiple sclerosis. Research published by UCLA Health describes a sex-linked gene that promotes inflammation in the brain. In their animal studies, the researchers identified a gene on the X chromosome linked to the production of inflammatory proteins in the brains of experimental animals. When the researchers deactivated the responsible gene, the neurodegenerative pathology in the animals was ameliorated. They propose that, since women carry two X chromosomes, this may help explain sex-related differences in diagnosis.
Estrogen may act as a protective agent against neurodegeneration. As women age, levels of estrogen decline, and exposure to cellular toxicity and the accumulation of amyloid proteins increases. Both phenomena may play a role in the increased incidence of AD in females. A report in The International Journal of Geriatric Psychiatry cited a study that looked at brain imaging in postmenopausal women and found that they have lower levels of gray matter than those who are premenstrual or perimenstrual. In addition, women who take hormone replacement therapy (HRT) have a lower incidence of AD than those who do not. The key is when the hormone replacement is prescribed. Dr. Rachel Buckley, a neurologist at Harvard, studied the impact of HRT and the later development of a protein(tau) related to Alzheimer’s disease. She found that the timing approach to prescribing HRT is essential. She and her colleagues found that HRT can be safely used to ease the symptoms of menopause, but should not be continued into older age. In her study, women who continued to receive HRT after age 70 had significantly higher levels of tau protein and suffered greater cognitive decline .
Sex Differences in Inflammatory Responses
Post-mortem brains of individuals with AD are characterized by neuroinflammation. In general, women have a more robust immune response than their male counterparts, a phenomenon observed in humans and in mouse studies.
One source of inflammation is an individual’s response to stress. Research from the University of California, Davis, identified changes in the adolescent brain during puberty that may reflect the differences in how men and women respond to stress. In an animal study, researchers found that female mice respond to stress by avoiding new situations. When the female mice were altered by implanting a testosterone probe, they behaved the same as their male counterparts when exposed to the same stressor.
Stress-Related Disorders
Epidemiological studies repeatedly support the fact that stress exposure, including everyday life stress, work stress, life events, and trauma , is associated with dementia risk. For example, studies of male veterans have demonstrated that PTSD is associated with increased dementia risk. A study in JAMA looked at the association of stress-related disorders and the eventual development of neurodegenerative diseases. They found that participants who experienced the most cumulative stress were more likely to develop a neurodegenerative disorder.
The types of stress were not uniform, but in general included chronic stress, such as that experienced by caring for a chronically ill spouse or family member. Acute, severe anxiety , such as military combat, and even a high number of stressful events over a lifetime, like job loss or the death of a parent in childhood , could contribute. Even childhood poverty, a source of chronic stress, has been linked to a higher risk of dementia in later life.
In a 2019 research article that reviewed the differences in how men and women experience emotional stress, the authors document that men and women differ in their risks for stress-related illness. Using MRI imaging, the researchers investigated sex-specific responses in participants' brains during exposure to an acute, sustained stressor. They found that men and women show different patterns of activity across brain regions when exposed to a stressor. This may be why women who endure stress over a period of time have an increased risk of neurodegenerative diseases like Alzheimer’s.
Preventative Measures
Even though women are diagnosed with Alzheimer’s more frequently than men, the risk is not solely based on the fact that we, as women, live longer. We cannot control our genetics ; they are fixed at birth. However, some factors have been shown to offset our genetic and hormonal risks.
Belloy, Michael E., et al. “Role of the X Chromosome in Alzheimer Disease Genetics.” JAMA Neurology , no. 10, American Medical Association (AMA), Oct. 2024, p. 1032.
Goldfarb, Elizabeth V., et al. “Sex Differences in Neural Stress Responses and Correlation with Subjective Stress and Stress Regulation.” Neurobiology of Stress , Elsevier BV, Nov. 2019, p. 100177.
Hodes, Georgia E., et al. “Sex Differences in Stress Response: Classical Mechanisms and Beyond.” Current Neuropharmacology , no. 3, Bentham Science Publishers Ltd., Mar. 2024, pp. 475–94.
Houston, Will. UCLA Health , 14 Oct. 2025.
Peeters, Geeske, et al. “Sex Differences in the Incidence and Prevalence of Young‐onset Alzheimer’s Disease: A Meta‐analysis.” International Journal of Geriatric Psychiatry , no. 1, Wiley, Aug. 2021.
Qi, Qing, et al. “Associations between Sex and Lifestyle Activities with Cognitive Reserve in Mid-Life Adults with Genetic Risk for Alzheimer’s Disease.” Alzheimer’s Research & Therapy, no. 1, Springer Science and Business Media LLC, Nov. 2024.
Song, Huan, et al. “Association of Stress-Related Disorders With Subsequent Neurodegenerative Diseases.” JAMA Neurology , no. 6, American Medical Association (AMA), June 2020, p. 700.
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Susan Trachman, M.D., is an associate professor at George Washington University and assistant professor at Virginia Commonwealth. She is a board-certified psychiatrist in adult and forensic psychiatry.
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