Two out of three Americans who are diagnosed with Alzheimer’s disease are women. And outside of a specific diagnosis, women tend to experience faster cognitive decline compared to men. The umbrella term for these symptoms affecting the brain, memory, and thinking is dementia.
For years, researchers thought this phenomenon was because women live longer than men on average, so they have more chances to show these symptoms. However, one research group from the Women’s Health Neuroscience Program at Texas A&M University is trying to find specific biological reasons for the prevalence of dementia in women.
They’re looking at female-specific therapies that, when combined with hormones, could actually prevent and reduce cognitive decline. This article will explore several research studies from this group in an attempt to uncover some of the reasons behind female dementia and what we can do about it.
Is there a dementia gender gap?
The burden of Alzheimer’s disease (AD) falls hardest on women. They make up the majority of Alzheimer’s patients (almost two-thirds!), and women over age 60 are almost el doble de probabilidades to develop AD as breast cancer.
Yes, women tend to live longer than men and dementia is a consequence of aging, but even among men and women living to the same age, women are más probable to be diagnosed with AD compared to men [1] [2]. Interestingly, women were no more likely to be diagnosed with general dementia compared to men. According to one study, the chances of developing dementia from a cause other than AD were comparable between women and men [1].
Yes, women tend to live longer than men and dementia is a consequence of aging, but even among men and women living to the same age, women are more likely to be diagnosed with AD compared to men.
Remember, dementia is the umbrella term for any cognitive decline. AD is the most common disease that causes dementia, and specifically refers to nerve cell damage in the brain. Plaque deposits of a sticky protein called beta-amyloid and twisted fibers called tau build up among the nerve cells and prevent them from communicating with each other. This makes it harder to remember and process information and causes mood and behavior changes.
Stroke is a major risk for dementia
Another explanation for the prevalence of AD and dementia among women is the incidence of stroke. The result of a blocked blood vessel, a stroke cuts off blood and oxygen to the brain which causes brain cells to die. After age 50, women are más probable to experience stroke compared to men. Stroke can increase the risk for further cognitive impairment and eventually dementia. The Asociación Americana del Corazón recently shared the risk of dementia may be up to three times higher following a stroke.
Women and men share some of the risks for stroke, like high blood pressure, but there are also risk factors unique to women. For example, pregnancy complications are one of the most important risk factors for stroke. Pregnancy puts extra strain on the heart as the woman’s blood volume increases, and preeclampsia can cause high blood pressure.
Early menopause (or when ovulation and menstruation stop before age 45) also increases the risk for stroke. Unsurprisingly, anticoncepción hormonal also doubles the risk for heart attack and stroke, because it interferes with biological hormone production and increases the risk for blood clots. The hormone estrógeno is protective for cardiovascular health, and the drop-off in estrogen production with menopause increases a woman’s risk for heart disease.
In fact, even aside from stroke, estrogen also plays a pretty significant role in brain health.
Estrogen’s role in protecting brain health después de accidente cerebrovascular
Estrógeno is known to have fairly protective effects on many of your body’s systems, including salud ósea, skin, mucous membranes, and salud cerebral. In the brain, estrogen suppresses inflammation by reducing the activity of brain immune cells called microglia, which limits nerve cell damage [3]. It also improves mitochondrial function, which can protect neurons from degeneration [3]. Several research groups have also been studying the protective effect of estrogen after stroke, specifically how estrogen can help reduce brain damage.
One of the leading researchers investigating women’s brain health, stroke, and dementia risk is Farida Sohrabji, PhD, at Texas A&M University. For years, she’s been asking questions about how estrogen is protective, when it becomes damaging, and how researchers can use this knowledge to discover sex-specific treatment options to reduce female dementia risk. Her team’s research largely uses rat models of young and aging female brains (younger rats of reproductive age, or older rats that no longer have reproductive cycles are used to mimic pre- and postmenopausal women, respectively). They use these rats to study what estrogen does in the brain after a stroke.
Using estrogen after stroke in younger rats
First, they found that estrogen protects the brain after stroke. Sohrabji’s team used younger rats with their ovaries removed (which meant they couldn’t produce their own estrogen), and induced stroke in these animals. Then, they measured the rat’s brain damage. These rats had worse brain damage than the control group, but when the research team gave the rats estrogen replacement therapy, the stroke outcomes were better. They thought they’d found the magic bullet: Why not give estrogen therapy to any female patient after a stroke?
Using estrogen after stroke in older rats
But Sohrabji’s team tested this theory in their older rats (postmenopausal ones) and saw the opposite. Estrogen was no longer protective! The research team’s big discovery was that estrogen’s effect on the brain changes from protective to harmful después de menopause [4]. Brain tissue damage, cognitive impairment, and neurodegeneration was more severe in older rats treated with estrogen.
Because both the younger rats without ovaries and the older postmenopausal rats both lacked the ability to produce their own estrogen, Sohrabji’s team hypothesized there must be some otros factor in the older rats that was missing that was required to help estrogen do its helpful work. And (spoiler alert!) they found one.
Because both the younger rats without ovaries and the older postmenopausal rats both lacked the ability to produce their own estrogen, Sohrabji’s team hypothesized there must be some otros factor in the older rats that was missing that was required to help estrogen do its helpful work.
Discovering a key brain-protective growth factor
The researchers found a protective growth factor called insulin-like growth factor (IGF-1) that is reduced in aging brains. It’s a hormone that has many functions, but in the brain, it turns on cell survival pathways to help neurons resist damage, helps the body create new neurons, and reduces inflammation [5].
Interestingly, estrogen también performs some of these roles. And, like estrogen, IGF-1 levels also naturally decline with age, so it would make sense that estrogen would “lose” its benefits in older females lacking IGF-1. When IGF-1 levels are high (as they are in younger animals) estrogen can trigger these protective pathways and reduce stroke damage. But when IGF-1 levels are low (as they are in older animals), estrogen may no longer be able to activate the same repair signals in the brain. In the latter environment, estrogen can shift from activating survival pathways to promoting inflammatory or damaging responses instead.
Consider IGF-1 “estrogen’s little helper”
So, Sohrabji’s team wondered, could it be that estrogen just needs a helper (i.e., IGF-1) to improve stroke outcomes in middle-aged brains? They did the experiment and they were right!
Older rats that received estrogen y IGF-1 no longer suffered the toxic effects of the estrogen-only treatment [4]. Sohrabji’s team’s research showed that the decline of estrogen’s effectiveness in the aging brain was correlated to the decline of IGF-1 levels. This introduced an important nuance to estrogen therapy: rather than being simply “good” or “bad,” estrogen’s effects on the brain appear to depend on timing and the hormonal environment in which it operates.
This introduced an important nuance to estrogen therapy: rather than being simply “good” or “bad,” estrogen’s effects on the brain appear to depend on timing and the hormonal environment in which it operates.
Further work from Sohrabji’s research group showed that IGF-1 actually protects the older brain in several ways after stroke. In middle-aged female rats, treatment with IGF-1 reduced inflammation and helped stabilize the blood-brain barrier (the protective layer that prevents harmful molecules from entering the brain). When this barrier breaks down after a stroke, inflammatory molecules can flood the brain and worsen injury. By strengthening this barrier and suppressing inflammatory cytokines, IGF-1 helped limit the spread of damage after stroke [6].
Dr. Sohrabji’s work supports the idea that the timing of exposure to exogenous estrogen matters. In other words, estrogen all the time isn’t what we want. Instead there’s a concept known as the “critical window” or timing hypothesis [7]. According to this idea, estrogen’s effects on the brain depend on when hormone exposure occurs relative to menopause. When estrogen is present during the reproductive years, it works alongside other protective signals like IGF-1 to support neuronal survival and recovery after injury. But once the hormonal environment of the brain changes with aging, the same hormone may produce very different effects.
What these findings mean for future medical research
For decades, much of what scientists understood about the brain (and about diseases like stroke and dementia) came from studies conducted primarily in males or in young animals. Historically, female animals were often excluded from biomedical research because their reproductive cycles were thought to introduce too much variability. As a result, male-only studies became common across many fields, especially neuroscience [8]. This imbalance has limited scientists’ ability to understand how biological sex and hormonal changes influence disease risk, brain injury, and recovery.
Dr. Sohrabji’s group is trying to change that. She’s actively working to promote inclusion of sex as a biological variable in scientific research, and raising awareness of sex differences in medical treatment. Her groundbreaking findings in Alzheimer’s research might lead to a future where the burden of disease no longer falls hardest on women.
Lo esencial
Understanding how these hormonal changes shape brain health is one of the reasons scientists are increasingly focusing on women (especially aging women!) in neuroscience research. The more we learn about how hormones influence the brain across a woman’s lifespan, the better we may be able to protect cognitive health and reduce dementia risk later in life.
