Why Does Alzheimer’s Disease Affect More Women Than Men?

Erin Reed-Geaghan, PhD

Northeast Ohio Medical University

  • Expert Advice
Published on:

Scientifically reviewed by Sharyn Rossi, PhD, BrightFocus Foundation

Key Takeaways

  • Women are disproportionately affected by Alzheimer’s disease (AD), comprising approximately two-thirds of all Alzheimer’s patients as well as the majority of caregivers for Alzheimer’s patients.
  • Women are nearly twice as likely as men to develop Alzheimer’s and live longer than men following an AD diagnosis.
  • The increased prevalence of Alzheimer’s among women likely arises through a combination of factors, including sex chromosomes, hormones, brain structure, and gender and life experiences. These factors are being explored as part of a new direction in Alzheimer’s research.
  • Women can lower their risk by focusing on the lifestyle factors under their control: eating a healthy diet; exercising both the body and the mind; and preventing or controlling other health conditions that contribute to AD, such as diabetes, heart disease, and depression.

Alzheimer’s disease is the seventh leading cause of death in the United States, with one in three seniors dying from AD or another form of dementia. Women are disproportionately affected by the disease, comprising approximately two-thirds of Alzheimer’s patients themselves and also serving as the majority of caregivers for people living with the disease. 

There are also extensive sex-linked differences in the way that Alzheimer’s behaves clinically in women versus men, as well as in neuroimaging results and underlying pathology. The cause of these sex-linked differences in AD risk and disease patterns are not entirely clear and are still being studied. Some possible factors include: 

  • genetic differences due to the composition of sex chromosomes (two X chromosomes in women versus one X and one Y in men)
  • sex hormones (estrogen versus testosterone)
  • differences in brain composition 
  • gender and life experiences

Studies funded by BrightFocus’ Alzheimer’s Disease Research program and others are underway to identify and explain how each of these factors contributes to Alzheimer’s’ outsized impact on women compared with men.

Age

Age is the single biggest risk factor for developing Alzheimer’s. On average, women live longer than men; however, the relationship between age and Alzheimer's is complicated. The increased prevalence (total number of cases) of Alzheimer's among women is a combination of the number of newly diagnosed cases (known as the incidence) and the number of those individuals already living with a diagnosis. Whether the incidence differs between men and women in the United States is unclear, but women do appear to live longer following an Alzheimer's diagnosis. 

One clue as to why women live longer with AD comes from a 2020 study that identified the KDM6A gene on the X chromosome as a potential resilience factor. Expression of KDM6A is increased among women and is associated with slower cognitive decline in an aging population. While living longer may account for some of the increased disease prevalence among women, it does not account for all of it, leading investigators to search for additional explanations. 

Differences in the Brain 

The brains of Alzheimer’s patients are characterized by the presence of beta-amyloid (Aß) plaques deposited between the brain cells, tangles of tau proteins inside the neurons, and extensive neuronal death. The expression of genes that contribute to the development of amyloid and tau pathology show a female bias and higher expression of these genes generates higher amounts of proteins involved in amyloid and tau pathology. Other factors, such as having defective versions of neural survival factors, may contribute to women being more susceptible to developing Alzheimer’s. 

The brains of Alzheimer’s patients are also characterized by neuroinflammation triggered by the brain’s long-lived resident immune cells, the microglia, probably in response to toxic Aß,tau proteins, and signals coming from sick, dying, and dead neurons. In several genetic studies of AD, this neuroinflammatory response and a correspondingly large number of immune-related genes correlated with increased Alzheimer’s risk. Women generally have more robust immune responses than men, and various mouse models of Alzheimer’s also show increased neuroinflammation in females. 

In addition, sex-linked characteristics have been discovered in microglia and whether or not these intrinsic differences in the immune cells and their inflammatory response contribute to Alzheimer’s in women is under active investigation. 

Genetic and Hormonal Risk Factors That Appear to be Sex-Based

After chronological age, the biggest risk factor for Alzheimer’s is apolipoprotein E4 (APOE4), a gene that produces a protein with a central role in moving cholesterol through the body. Importantly, it is sex-linked, having a stronger effect on women than it does men. It is also differentially expressed across races and ethnicities – another line of exciting research that will require attention when designing clinical trials and developing therapies. 

It takes decades for Alzheimer’s to progress from early disease to clinical symptoms such as memory loss, confusion, language/speech impairments, and shortened attention span. At about the same time that preclinical AD may be developing, many women go through menopause, and scientists think the loss of estrogen may expose women to a critical period of vulnerability for the development of Alzheimer’s. However, replacing estrogen has produced conflicting results with regard to cognition, and the impact of post-menopausal estrogen reduction is still being studied. In contrast, androgens (i.e., male sex hormones, including testosterone) are neuroprotective in late life and may help preserve brain health and function in men, leading to lower levels of disease. 

2022 study implicated a different hormone, the pituitary gonadotrophin follicle-stimulating hormone (FSH), whose levels rapidly increase in the perimenopausal phase and are strongly associated with the onset of Alzheimer’s. FSH acts on neurons to impair cognition; studies in a mouse model of AD have shown that blocking its action may reduce Alzheimer’s-like memory loss. This reveals yet another potential explanation for why women may be disproportionally affected and provides a potentially novel opportunity to treat Alzheimer’s in women. 

The Bottom Line

The interpretation of research findings is further complicated by the context in which these biological variables occur. Typically, research results cannot account for social and lifestyle factors including education, occupation, social activities, diet, and exercise–variables that may act in concert with biological factors to increase or minimize Alzheimer’s risk.  

Furthermore, not only do these factors contribute to disease prevalence, but they likely impact the response to treatment. Men and women differ in how they process and distribute drugs throughout their bodies and in their response to drugs. This requires improved sex-specific analyses during clinical trials and considerations of sex in patient responses to treatment. Ultimately, by having an improved awareness of potential sex-based risk factors, and how they potentially contribute to the disease, physicians can better assess their patients’ Alzheimer’s risk, detect disease, and provide personalized prevention and treatment plans.

In addition to seeking personalized care of the sort described above, women can lower their risk of Alzheimer's by focusing on the lifestyle factors under their control. Some healthy lifestyle actions you can do now include:

  • Eat a varied, nutritious, and low-glycemic diet. Include foods that contain vitamins C, D, and E, omega-3 fats, and the antioxidants lutein and zeaxanthin.
  • Get regular exercise and maintain a healthy weight. This will improve not only your immune system and blood pressure, but your brain and eye health. 
  • Get enough good quality sleep, as recommended for your age group. Research has pointed to the importance of regular deep sleep to flush the brain of waste material and toxins and to break down and dispose of Aß plaques that are seen in early Alzheimer’s.
  • Keep your mind active. While the debate continues over whether cognitive exercises will help lower the risk of Alzheimer's disease, keeping your mind nimble will enhance your overall well-being. You can also check out these memory games.
  • Optimize your overall health throughout adulthood, and especially by middle age, by working to prevent or manage diseases and conditions that increase the risk of Alzheimer’s, including diabetes, heart disease, traumatic brain injury (concussions), depression, and more.

Resources


About BrightFocus Foundation

BrightFocus Foundation is a premier nonprofit funder of research to defeat Alzheimer’s, macular degeneration, and glaucoma worldwide. Through its flagship research programs—Alzheimer’s Disease Research, National Glaucoma Research, and Macular Degeneration Research—the Foundation is currently supporting a $75 million portfolio of 287 scientific projects worldwide. BrightFocus has awarded nearly $275 million in groundbreaking medical research funding since inception and shares the latest research findings, expert information, and bilingual disease resources to empower the millions impacted by these devasting diseases worldwide. Join our community at brightfocus.org.
 


 

About the Author

Erin Reed-Geaghan, PhD, is an Assistant Professor of Pharmaceutical Sciences at Northeast Ohio Medical University. She is the recipient of a BrightFocus Alzheimer’s Disease Research grant to identify the developmental factors that program immune cell responses leading to sex differences in Alzheimer’s disease onset and progression.

 

 

The information provided here is a public service of BrightFocus Foundation and should not in any way substitute for personalized advice of a qualified healthcare professional; it is not intended to constitute medical advice. Please consult your physician for personalized medical advice. BrightFocus Foundation does not endorse any medical product, therapy, or resources mentioned or listed in this article. All medications and supplements should only be taken under medical supervision. Also, although we make every effort to keep the medical information on our website updated, we cannot guarantee that the posted information reflects the most up-to-date research. 

These articles do not imply an endorsement of BrightFocus by the author or their institution, nor do they imply an endorsement of the institution or author by BrightFocus.

Some of the content may be adapted from other sources, which will be clearly identified within the article.

 

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