More women than men develop Alzheimer’s disease, a disparity that persists even when accounting for women’s longer lifespans. While factors like educational attainment and socioeconomic status likely play a role, experts believe the difference extends beyond these variables. “There’s a lot to suggest that the ratio wouldn’t be one-to-one even under completely equal conditions,” says Steffi Riedel-Heller of the University of Leipzig.
Approximately two-thirds of all individuals with Alzheimer’s are women. The disease is most often diagnosed after age 65, with incidence increasing significantly after age 80. A key contributor to this prevalence is the difference in lifespan between men and women. According to German mortality tables from 2022/2024, the average life expectancy at birth is 78.5 years for men and 83.2 years for women.
Johannes Levin from the German Center for Neurodegenerative Diseases (DZNE) explains that biological factors aren’t solely responsible for this difference. He suggests that overall risk behavior plays a significant role, noting that men generally live less healthy and more dangerous lives. Groups with healthier lifestyles, such as monks, exhibit a life expectancy comparable to that of women.
However, even when adjusting for lifespan, a difference remains: women are more likely to be diagnosed with Alzheimer’s within the same age groups. The ratio is approximately 60:40, according to neurologist Wenzel Glanz of the University Hospital Magdeburg. While definitive answers remain elusive, a growing body of evidence suggests the issue is complex.
The Role of Genes – An Often Underestimated Factor
The APOE gene is considered a crucial factor in Alzheimer’s disease, potentially influencing up to 70 to 90 percent of cases, according to an analysis published in npj Dementia. We find three common types of the gene – E2, E3, and E4 – and individuals typically inherit two APOE genes, resulting in various combinations.
Carrying one or two E4 variants significantly increases the risk of Alzheimer’s compared to having two copies of the E3 variant. Conversely, individuals with the E2 variant have a lower risk. “The E4 variant of APOE is recognized by dementia researchers as harmful,” explains Dylan Williams of University College London, the study’s lead author. “But many diseases would not occur without the additional influence of the common E3 allele, which is typically incorrectly assessed as neutral with respect to Alzheimer’s risk.”
Petra Stute of the University Hospital for Gynecology in Bern notes that approximately 60 percent of people have the E3/E3 combination, 20 to 30 percent have E3/E4, and 2 percent have E4/E4. The E2/E3 or E2/E2 combinations affect about 5 percent of the population. A recent study of “Super-Agers” – individuals over 80 with cognitive function comparable to those 20 or 30 years younger – found they were more likely to carry the E2 variant and less likely to carry the E4 variant.
“The extent to which APOE has been researched in relation to Alzheimer’s or as a drug target is clearly disproportionate to its actual importance,” Williams states. Previous studies have shown that the protein derived from the E4 gene promotes amyloid plaque formation in the brain. Accumulations of beta-amyloid and tau proteins are hallmarks of Alzheimer’s disease. The E4 protein also disrupts fat and energy processing in brain cells and promotes inflammation, potentially damaging neurons and increasing susceptibility to dementia.
The APOE4 variant increases the risk of Alzheimer’s more significantly in women than in men, Riedel-Heller adds, with researchers suggesting hormonal influences as a potential cause.
Is Hormone Therapy a Consideration?
Women in their 60s are approximately twice as likely to develop Alzheimer’s during their remaining lifetime as they are to develop breast cancer, according to the Alzheimer’s Association. Both diseases are influenced by hormones. The onset of menopause is accompanied by a decline in estradiol levels, an estrogen that regulates the expression of the APOE gene. Lower estradiol levels lead to increased protein production, potentially exacerbating the risk for APOE4 carriers.
A research team led by Stute suggests that hormone therapy could be a targeted strategy to mitigate Alzheimer’s risk, particularly when initiated soon after menopause, as detailed in Gynäkologische Endokrinologie. However, further studies are needed to confirm this hypothesis.
A review study published in The Lancet Healthy Longevity, analyzing data from over one million patients, found no evidence that hormone therapy during menopause generally increases or decreases the risk of dementia. The research team, led by Melissa Melville of University College London, noted the need for high-quality, long-term research to draw definitive conclusions.
Levin notes that early menopause – before age 45 – is associated with an increased Alzheimer’s risk, but the effect is not substantial. He cautions against initiating hormone therapy solely for Alzheimer’s prevention.
The Glymphatic System – When the Brain’s Drainage System Slows Down
During deep sleep, the brain is flushed with clear cerebrospinal fluid (CSF), removing waste products like beta-amyloid and tau proteins through a system called the glymphatic system. Sleep deficits can disrupt this process.
Riedel-Heller suggests that hormonal influences may also affect the glymphatic system, as sleep disturbances are a common symptom of menopause. Hormone therapy can significantly reduce these disturbances.
Cancer and Alzheimer’s – Could There Be a Connection?
Research suggests a potential protective effect of cancer against Alzheimer’s disease. Studies in mice have shown that a molecule produced by cancer cells protects the brain from developing plaques, as reported in Cell. However, confirmation in humans is still needed.
Data from 2020 indicated an 11 percent lower incidence of Alzheimer’s in individuals with a cancer diagnosis. However, this could be due to cancer patients dying earlier, before Alzheimer’s would be diagnosed. Women are generally less likely to develop cancer than men, potentially contributing to the observed disparity in Alzheimer’s rates.
What About Education, Income, Exercise, and Diet?
Numerous factors are associated with an increased risk of dementia, including lower education levels, hearing loss, high blood pressure, smoking, obesity, depression, lack of physical activity, diabetes, excessive alcohol consumption, traumatic brain injury, air pollution, and social isolation. Untreated vision loss and high LDL cholesterol levels are also risk factors, according to a report in The Lancet Commissions.
The potential for prevention is high, with studies suggesting that nearly half of all dementia cases could be prevented by eliminating these 14 risk factors. The authors attribute the higher Alzheimer’s rates in women, in part, to their historically lower levels of education.
Higher education is linked to higher income and better access to healthcare, healthier food, and cleaner living environments. Lower socioeconomic status is often associated with chronic stress, psychological burden, and reduced social participation, all of which can harm brain health.
Today’s 80-year-old women had fewer educational and career opportunities in their youth, Glanz points out. The impact of these changes on younger generations remains to be seen. It is reasonable to expect a positive effect, although the extent is difficult to quantify due to the many other influencing factors, Levin, a neurologist at Ludwig Maximilian University of Munich, suggests.
Both men and women are likely to benefit from healthier lifestyles – less smoking, less alcohol, and more exercise – as Glanz anticipates. However, the genetic component of the disease suggests that the effects may be modest. The improved educational background may influence the age of diagnosis: Alzheimer’s often becomes apparent when language skills decline, and women generally have a stronger linguistic foundation.
Late Diagnosis – Diminished Opportunities
Women generally have better verbal skills and memory than men, Glanz explains. Alzheimer’s may manifest later in women, and the initial screening tests used by general practitioners are language-based. This can lead to a delayed diagnosis.
This delay can create the impression that the disease progresses more rapidly in women, Levin notes. “Skills are lost more quickly, and affected individuals become more dependent on care sooner.” What we have is particularly concerning given the need for early intervention with new Alzheimer’s treatments like lecanemab and donanemab.
Glanz believes that the initial tests need to be adapted. Even with improvements, women are likely to seek medical attention at later stages of the disease. The increasing use of social media and its associated risks – sleep deprivation and lack of physical activity – could also play a role. On the medical front, more effective therapies are on the horizon, but a cure remains distant, Glanz concludes.
