Women and Alzheimer's: Brain Health News Update 2021 Part 2, A Closer Look at Women's Brains

Written by Annie Fenn, M.D.

It has been known for decades that women are more likely to develop Alzheimer's than men.  In fact, two thirds of Alzheimer's patients are women.  In this 3-part series, I discuss several scientific papers that shed light on the unique vulnerabilities of the female brain and the impact of hormones on the aging brain.  In this 2nd article, I'll explore how women's brains are vulnerable to Alzheimer's due to menopause, and also how they are resilient.

A Closer Look at Women's Brains

Hormonal changes due to menopause make women more vulnerable to Alzheimer’s

What does the Estrogen Hypothesis look like in the brain of a woman in real life? To find out, Dr. Lisa Mosconi and her colleagues employed advanced technology to compare the brains of women and men. Thanks to high tech positron emission tomography (PET) scans and functional magnetic resonance imaging (MRI), they were able to look at brain activity through the lens of blood flow.

In this prospective study published in the journal Neurology in 2020, Mosconi and her colleagues examined the brains of 121 cognitively normal women and men between the ages of 40 and 65.1 They measured brain changes—called Alzheimer's biomarkers—like amyloid protein build-up and low glucose metabolism. Each participant was fully evaluated for other factors known to impact Alzheimer’s risk, such as menopausal status, ApoE4 status, smoking, exercise, and how closely they followed a Mediterranean-style dietary pattern (a known predictor of reduced Alzheimer’s risk).

This paper gets at the heart of the issue of how women and men differ in their vulnerabilities to Alzheimer’s. When these middle-aged women and men were matched in all other risk factors, their brains portrayed a different story of how Alzheimer’s develops, decades before the first symptoms. The women who were going through menopause had the most dramatic biomarker abnormalities—impaired glucose metabolism, an overall smaller brain volume, and more plaques and tangles. The life stage of menopause, it appears, is a “window of opportunity” for these adverse brain changes to begin. Other studies support this finding, pointing to an earlier age of the onset of menopause as an important risk factor for Alzheimer’s later in life.

This study also looks at a woman's risk of Alzheimer’s if she has had a hysterectomy or takes hormone replacement therapy (HRT). The postmenopausal women who took HRT had 31% greater glucose metabolism than the postmenopausal women who did not take HRT. HRT users also had greater brain volumes when compared to nonusers. If a woman had a hysterectomy (without HRT after), the trend was to have a lower brain volume, less glucose activity, and more amyloid deposition, when compared to women who had not had a hysterectomy. The timing of HRT seems to be key: hormone replacement is most beneficial if taken as soon as a woman has become menopausal, either naturally or secondary to surgery.

Women's Brains and the Silver Lining of Menopause

Mosconi’s most recent paper, published in the journal Nature Scientific Reports in June 2021, illustrates that women’s brains aren’t just vulnerable at menopause, they are also resilient.2 By studying cognitively healthy women before and after menopause, she and her colleagues discovered changes in the brain’s energy consumption, structure, and connectivity. The good news is this: women’s brains have the ability to compensate for these changes. “Our study suggests that the brain has the ability to find a new normal after menopause in most women,” says Dr. Mosconi.

The Take-Away for Brain Health

The menopausal transition may be a window of opportunity for setting up the pathological changes that lead to Alzheimer’s later. When estrogen plummets at menopause, it not only triggers the classic symptoms, like hot flashes and memory loss, it leads to vulnerabilities in the actual structure of the brain. Identifying women at heightened Alzheimer’s risk, especially decades ahead of time, will help us address how to optimize healthy brain aging.

New research shows that women’s brains have the ability to adapt to these menopausal brain changes. That’s why it’s especially crucial for women approaching menopause to proactively care for their brains with a lifestyle that includes neuroprotective foods.


  1. Rahman, A., Schelbaum, E., Hoffman, K., et al., Sex-driven modifiers of Alzheimer risk. Neurology, 2020, 95, e166 LP-e178.
  2. Mosconi, L., Berti, V., Dyke, J., et al., Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition. Sci. Rep., 2021, 11, 1–16.
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