With women making up two-thirds of Alzheimer’s cases, the mystery continues: Why are they more vulnerable to the disease than men?
Some researchers are now focusing on estrogen, and what happens when a woman’s body enters menopause. They say there are steps women can take in their 40s to help prevent dementia decades later.
Estrogen is a protective hormone that actually goes inside a woman’s brain, stimulating growth, health and plasticity, and keeping it expanding rather than shrinking as a woman ages, said Lisa Mosconi, associate director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical College/NewYork-Presbyterian Hospital.
But the natural drop in estrogen during menopause means women lose this extra “crucially important” layer of protection, she noted.
“Alzheimer’s doesn’t turn on in your brain when you’re 80 years old. Alzheimer’s begins when we’re 40 or 50 years old. It’s not bad enough that you get symptoms, but the process starts in mid-life, which is exactly when women go through menopause,” Mosconi told TODAY.
Women who had not entered menopause showed strong energy inside their brains, called brain glucose metabolism. These women also had no evidence of the amyloid plaques associated with Alzheimer’s.
But the brain metabolism of women in perimenopause declined by 20-30 percent and they started showing some plaques. Women who had already entered menopause had the biggest drop in brain metabolism — almost 50 percent in some cases, Mosconi said, and more plaques.
None of the men in the study showed any comparable changes.
The findings suggest perimenopause — the period when a woman starts to produce less estrogen, usually in her 40s — may be a critical point in whether she’ll go on to develop Alzheimer’s or not.
“For many women, this is a very important transition state when your brain is going through a time where it has to completely reset and adjust to a new low, in a way. Some women go through that really well and some women do not,” Mosconi noted.
Other experts were more cautious. The evidence on whether estrogen plays a protective role in women’s brains is mixed, said Heather Snyder, senior director of medical and scientific operations at the Alzheimer’s Association who oversees the group’s Women’s Alzheimer’s Research Initiative.
“This is complex biology… an incredibly important area to understand,” Snyder said.
“We do know there are hormonal changes that happen and there is a response that happens in the brain. Whether this is making the brain more vulnerable to changes that we then see in diseases like Alzheimer’s, that’s the big question.”
Besides hormones, there may be other possible factors in why more women have Alzheimer’s, including differences in how men’s and women’s brains are wired, their immune system responses and their brain metabolisms, Snyder added.
But for Mosconi, it’s clear perimenopause may be the time for medical or lifestyle intervention.
One potential option is hormone replacement therapy, a controversial choice. Once routinely prescribed for women as a way to relieve menopause symptoms and protect their health by boosting their low estrogen levels, HRT frightened many patients after a large study showed it raised the risk of cancer, especially breast cancer and didn’t lower the risk of heart disease.
But recent research found HRT did not affect women's death rates.
There’s also evidence that starting HRT before menopause is associated with a reduced risk of Alzheimer’s, Mosconi said.
The argument for embracing HRT to protect a woman’s brain is a compelling one, noted nutrition expert and TODAY contributor Kristin Kirkpatrick.
Women considering this option should talk to their doctors and get a thorough medical screening, all of the experts said. Women with a family history of certain breast cancer, heart disease, blood clots and strokes would likely not be good candidates.
Again, Snyder was cautious about turning to HRT during perimenopause for brain health.
“There’s really no data that can help support that idea,” Snyder said. “In terms of what this is going to do for your brain, we don’t know.”
Mosconi, who is also the author of "Brain Food: The Surprising Science of Eating for Cognitive Power," is a big believer diet can help. She advised lifestyle changes before considering medication.
“Not many women know that some HRT formulations actually derive from the urine of pregnant horses,” she said. “I’d much rather have a salad and some hummus than taking medicine from horses.”
Women seeking more estrogen can get it from phytoestrogens, or plant-based compounds. Soy beans are the best natural source of estrogen from plants, but you can also get it from chickpeas, flax seeds, vegetables and whole grains, Mosconi said. At 40, she is following an eating regimen naturally high in phyotestrogens.
Again, check with your doctor to see if eating estrogenic foods would be a safe practice for you.
"The connection between hormones and the brain is not really mainstream medicine. I think we're just starting to understand it," Mosconi said.
Recognized lifestyle changes to prevent Alzheimer’s include regular exercise and a heart-healthy diet that emphasizes whole grains, fruits and vegetables, fish, nuts, olive oil and other healthy fats, the Alzheimer’s Association advises. Getting enough sleep, social connections and intellectual stimulation is important, too.