En español | Of the 5.5 million people with Alzheimer's in the United States, it's long been known that most of them — currently 3.4 million — are women. Research presented today at the Alzheimer's Association International Conference in Chicago offered some provocative insight into why this might be, connecting dementia risk for the first time to reproductive factors such as the number of pregnancies or miscarriages a woman has over her lifetime.
Maria Carrillo, chief science expert of the Alzheimer's Association, framed the discussion this way: "We’ve always talked about women's issues and the knowledge that two-thirds of Americans with Alzheimer's are women. Why is there that increased risk for them? This grouping of studies today really points to the fact that there’s more to it than just women living longer."
One of the most surprising pieces of news — released in the findings of two separate studies — was how pregnancy might offer some protection against developing dementia later in life, and that the reasons for this could possibly extend beyond the role of estrogen to things like how the immune system regulates itself long-term after changes kicked off by pregnancy.
But estrogen, long linked to cognitive function in women, was indeed the focus of other studies, with one underscoring what is becoming standard advice, derived from many avenues of research, for the timing of hormone replacement therapy for menopausal women (in a nutshell: sooner rather than later).
Finally, in a slightly different vein of gender-based work, researchers at the University of Illinois, Chicago found that women — through innate advantages in verbal ability — score better on standard tests given to diagnose the early stages of dementia, even when brain scans show they are at the same stage of the disease as lower-scoring men. Their results point to the need for harder-to-meet cutoff points for women only — in this particular case, for their own good.
Here a few of the takeaways in a bit more detail.
Pregnancies seem to offer some protection against Alzheimer's, and miscarriages may — or may not — increase your risk of dementia.
In the first large-scale epidemiological look at dementia risk and reproductive history, Paola Gilsanz, a scientist with Kaiser Permanente Northern California, and Rachel Whitmer, professor of epidemiology at the University of California, Davis, evaluated data on nearly 15,000 women between the ages of 40 to 55 collected over nearly a decade to find that women with three or more children had a 12 percent lower risk of dementia compared with women who had only one child. (There was a small, but not significant, benefit for having had two kids.)
As for why this might be the case, the scientists speculate that, among other possible reasons, successful pregnancies could reflect better overall health for the population of women studied, who gave birth in the 1960s and '70s. Or more births could — in theory — be related to increased exposure to a specific kind of estrogen that spikes with pregnancies.
Their work also uncovered a 9 percent greater risk for later dementia for each miscarriage a woman endured, and showed a 28 percent greater risk for women who entered natural menopause at age 45 or younger. While the researchers were clear to point out that their work is observational, they say it fits into a larger push for looking at dementia risk "across the lifespan," and for looking further into the reasons that men and women reflect different rates of Alzheimer's.
As Whitmer explains it, for a long time it was assumed that the men who made it to their 80s — who hadn't died of cardiovascular disease — were simply a more robust and somewhat "special" group, and that their relative hardiness explained why women had more dementia than they did. "But in the last few years," Whitmer says, "there’s been a body of evidence coming forward that there could be something specific about being female that is linked to these biological risk factors." As a result, "the field needs to step back, and really ask what is it beyond living longer that explains why more women have dementia."
In a separate study, Molly Fox, an assistant professor of psychiatry and biobehavioral sciences at UCLA, found a similar protective function with pregnancy, finding that each pregnancy in a survey of British women offered a 5.5 percent reduction in future dementia. Her work hypothesized that the positive effect stemmed from effects on the immune system during pregnancy, related to how it reorganizes itself "to tolerate an invader" — a baby — "that is 50 percent foreign DNA." It could be, Fox theorizes, that such immunosuppression during pregnancy could persist for the duration of a woman's life as a more finely tuned ability to regulate inflammation — and thereby avoid, say, the kind of harmful inflammation related to dementia-related plaque buildup in the brain.
Hormone therapy can be harmful for cognition — or not — depending on when you take it.
Carey E. Gleason, of the Wisconsin Alzheimer’s Disease Research Center at the University of Wisconsin School of Medicine and Public Health, mined two separate studies on estrogen and menopausal women to find no negative effect on cognition in women who initiated hormone therapy between the ages of 50 and 54. That is different from the conclusion of one highly influential 2002 study that stopped most doctors from giving hormones to women after finding a variety of harms, including reduced cognitive function. Those who started between 65 and 79, however, did show clear reductions in global cognition, working memory and executive function.
Within the context of other studies showing that cognition can indeed take a hit when women enter menopause, Gleason says the findings on positive earlier hormone therapy could be useful information. What she says is ultimately needed is a “personalized” approach toward hormone therapy, since other factors — like whether you have diabetes, or if you carry the APOE gene, which is related to dementia — can affect how your body might respond to such hormonal medications.
Women can "hide" symptoms of Alzheimer's through their superior verbal skills, at least in the early stages of the disease.
Using a verbal memory test commonly given to diagnose the early stages of dementia, Erin Sundermann, a project scientist at the University of California San Diego School of Medicine, found that healthy adult women score higher than healthy adult men overall, and that women appear to sustain that edge in the early stages of dementia, known as mild cognitive impairment (MCI).
On what Sundermann describes as "a list-learning test where participants are asked to learn and remember a list of words immediately and then after a delay period," women whose brain scans showed them to be at the MCI stage were able to recall 38 of 75 words, while men at the same stage recalled only 32.
However, at later stages of cognitive impairment, the advantage disappeared. That particular finding could help explain why women show a more rapid decline after being diagnosed with Alzheimer's; by the time the disease is diagnosed, they are much farther along than the earlier test would have indicated. As Sundermann says, "Our research suggests that women may be diagnosed later in the Alzheimer's trajectory compared to men because they are better equipped to compensate for brain insult and perform normally on verbal memory tests despite evidence of pathology in the brain."
She also says that her research highlights the need for sex-specific "cut scores" in diagnostic tests for men and women. Having those would help with early detection of the disease in women, ideally in the window during which "currently available treatments are likely to be the most beneficial." When her researchers applied such an intentional double standard in the lab, diagnostic accuracy improved in both sexes.