Alzheimer’s disease is the most common form of dementia. It is a condition that causes the brain to gradually shrink and its cells to die. It is typically caused by a dangerous buildup of amyloid proteins around the brain cells, and tau proteins inside them. According to 2023 Alzheimer’s Association Facts and Figures, an estimated 6.7 million Americans aged 65 and older are living with Alzheimer’s, and someone develops it every 68 seconds. According to the National Institute on Aging, it is the seventh leading cause of death in the United States.
While this disease can affect absolutely anyone, women are at a higher risk of developing it during their lifetime. Research shows that this degenerative disease is twice as common in women than it is in men.
A study that followed 16, 926 people in Sweden found that women around the age of 80 were more likely to be diagnosed with Alzheimer’s disease compared to men of the same age. Another study found that one’s chance of developing Alzheimer’s disease over seven years was greater in women compared to men.
On top of this, a European meta-analysis found that approximately 13 out of 1, 000 women developed Alzheimer’s each year, compared to only 7 men. Why do we see disproportionate numbers across gender?
Combination of Various Factors
There is no single reason as to why Alzheimer’s is more prevalent in women, however, there are a few reasons which may effectively explain the link.
According to Nikhil Palekar, M.D., director of the Stony Brook Center of Excellence for Alzheimer’s Disease, “the risk of Alzheimer’s increases with age, and women tend to live longer than men.” There are a lot older women living in our society, with Harvard Medical School averaging this at 5.7 million. With your risk of Alzheimer’s increasing as you get older, this could explain the disparities in numbers. While this may seem like a clear-cut explanation, it is extremely vague. As such, it cannot be the only answer as to why women are more likely than men to develop Alzheimer’s disease. This has led to the discovery of another possible cause: differences in brain structure.
2. Brain Region Structure
A recent Yale study managed to identify key structural differences to explain women being at a higher risk for Alzheimer’s. Led by Carolyn Fredericks, assistant professor of neurology and women’s health research at Yale, the study analyzed differences in a specific area highly linked to the disease: the Default Mode Network.
This is a set of brain regions that interact to not only bring about a wakeful rest (including daydreaming) but also act as a key for short-term memory functions. When researchers compared changes in these regions over time, they found distinctions between male and female brain connectivity. Surprisingly, a healthy woman showcased a connectivity pattern that was similar to preclinical Alzheimer’s patients. According to Fredericks, “that pattern of relative posterior connectivity has been seen before in people with preclinical Alzheimer’s disease.” This makes it a potential source of the predisposition of women affected by the disease.
Fredericks and her team analyzed large, cross-sectional data and relied on banks for neural scans from the Human Connectome Project Aging cohort. Including scans from over 595 healthy adults, these banks helped researchers examine intrinsic connectivity distribution. These scans act as an explanatory tool for detecting brain tissue and function.
3. Brain Protein Content
Alzheimer’s is believed to be caused by an abnormal build-up of protein in and around the brain cells. A study led by researchers at the Massachusetts General Hospital, Boston, found that levels of one defining protein seen in Alzheimer’s disease – tau (in the entorhinal cortex, an area of the brain involved in memory) – were higher in women than in men.
The researchers examined positron emission tomography (PET) brain scans from two studies, the Harvard Aging Brain Study, and the Alzheimer’s Disease Neuroimaging Initiative. These had a total of 296 older adults, comprising 173 women. All participants demonstrated normal cognitive function when they first received a brain scan to measure tau, and a PET scan to measure beta-amyloid, another Alzheimer’s-related protein.
This isn’t the only study to showcase this. A professor of pathology at Case Western Reserve University explained that the scientific community has long considered tau, the brain protein, as a hallmark signature of Alzheimer’s. This is because when too much of it accumulates in the brain, it becomes toxic. It has been found that it builds up faster in women when compared to men. This can occur even before the onset of symptoms of the disease.
David Kang, Ph.D., co-authored a study that looked at the link between the protein and Alzheimer’s in women. Kang shares that “what we found is that an enzyme called USP11 is expressed at naturally higher levels in females compared to males, and this… causes an increase in tau pathology and greater susceptibility to Alzheimer’s disease.”
USP11, also known as ubiquitin-specific peptidase 11, works to remove ubiquitin, a small protein tag. Ubiquitin typically works to degrade a protein, however, when it is removed, the proteins begin to accumulate. Since women naturally exhibit higher levels of USP11, this can trigger a toxic buildup of protein clumps, which is yet another hallmark of Alzheimer’s disease.
Shae Datta, M.D., who is the co-director of New York University Langone’s Concussion Center, simplifies this for us. She states that “in simpler terms, having two X chromosomes increases the levels of an enzyme that causes protein aggregation in the brain, which leads to Alzheimer’s.”
4. Beta-amyloid content
Women have stronger immune systems than men. As part of this stronger system, women may tend to have more amyloid plaques than men. One form of this, namely beta-amyloid 42, is believed to be extremely toxic. In the Alzheimer’s brain, abnormal levels of this naturally occurring protein clump together, leading to the formation of plaques that build up between neurons, disrupting cell function.
Experts believe that people with more beta-amyloid also have more tau and that these proteins interact early in Alzheimer’s disease progression – years before memory loss and other related symptoms appear. This theory gives us another possible explanation as to why women have a greater risk of developing Alzheimer’s disease.
Gender Gaps in Research and Healthcare
Women bear a disproportionate weight of the impact of this disease. To make matters worse, medical research on gender differences is often overlooked. No medical intervention will treat two people the same way, and this applies to gender differences too. While the above have been cited as possible reasons for the difference in numbers, more research needs to be conducted to confirm their validity.
The bottom line
With these continuously increasing numbers, women need to prioritize their overall health and well-being. From exercising regularly, to avoiding smoking and drinking, and improving their diet, there are interventions that can be implemented as preventative measures, and treatments too. It’s all about finding what works for you and ensuring that your individual health needs are met. Prioritize paying your doctor a visit to establish your risk level and what you can do to combat it.