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The greatest known risk factor for Alzheimer’s disease is, unsurprisingly, age. The second is gender. At age 65, healthy women have a one in six chance of developing the memory loss disease during their lifetime, compared with a one in 11 chance for men — a statistic that cannot be solely explained by the fact that women generally live longer than men. Other biological factors appear to be at play.

In a study published this month in the journal Menopause, researchers at Brigham and Women’s Hospital and Harvard Medical School explore what may be a related phenomenon: how menopause affects memory. According to the study, between the ages of 45 and 55, women outperform men in memory function, but some types of memory appear to fade as estrogen declines. Postmenopausal women were worse at learning new information and retrieving new memories than premenopausal women.

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The findings suggest that hormonal changes play an important role in maintaining memory in women, and could help identify which women are at highest risk for developing Alzheimer’s or other forms of memory loss, the authors say.

“Understanding healthy aging will provide clues to how the brain goes awry in men and women, and who might be at highest risk for the disease earlier in life,” says senior author Jill Goldstein, director of research at the Connors Center for Women’s Health and Gender Biology at the Brigham, and a professor of psychiatry and medicine at HMS.

Many studies have found that women perform better on verbal memory tasks than men — from post-puberty through old age — but little is known about how that memory is affected by hormonal changes. Goldstein and colleagues invited 212 healthy men and women, ages 45 to 55, from the New England Family Study to participate in a battery of verbal memory and learning tests, such as associating names with faces, learning new information, and recall of that information.

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As expected, women outperformed men of the same age on all the cognitive measures. But women who had not yet experienced menopause performed better than postmenopausal women in two key areas of memory: the ability to learn new associative memories — relationships between unrelated items, like a face and a name — and to retrieve them. That performance decline was associated with lower levels of estradiol, the main form of estrogen in the brain, in the blood of the participants.

The finding supports the idea that “brain fog,” a type of forgetfulness that springs up during midlife, may be associated with hormonal changes rather than job stress or other midlife factors. The researchers are now studying the postmenopausal women who performed best on the memory tests to see if they can discover biological factors, such as genetics or the immune system, that may help maintain a strong memory.

The impact of gender will be a key part of understanding risk for dementia and finding treatments for it, Goldstein emphasizes. “We’re in this day and age of precision medicine. What could be more central than one’s sex in developing more efficacious treatments?”


Megan Scudellari is a science reporter based in Needham. You can follow her on Twitter @Scudellari.