Women’s Aging Brains: Study finds adult female brain is on average a few years younger than the male brain. And new link found between menopause and far greater incidence of Alzheimer’s among women.

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The News:

Possibly to the chagrin of some men, a new study finds that women tend to have more youthful brains than their male counterparts–at least when it comes to metabolism.

While age reduces the metabolism of all brains, women retain a higher rate throughout the lifespan, researchers reported this week in the journal Proceedings of the National Academy of Sciences.

“Females had a younger brain age relative to males,” says Dr. Manu Goyal, an assistant professor of radiology and neurology at Washington University School of Medicine in St. Louis.

And that may mean women are better equipped to learn and be creative in later life, he says.

The finding is “great news for many women,” says Roberta Diaz Brinton, who wasn’t connected with the study and directs the Center for Innovation in Brain Science at the University of Arizona Health Sciences. But she cautions that even though women’s brain metabolism is higher overall, some women’s brains experience a dramatic metabolic decline around menopause, leaving them vulnerable to Alzheimer’s.

The study came after Goyal and a team of researchers studied the brain scans of 205 people whose ages ranged from 20 to 82. Positron emission tomography scans of these people assessed metabolism by measuring how much oxygen and glucose was being used at many different locations in the brain.

The team initially hoped to use the metabolic information to predict a person’s age. So they had a computer study how metabolism changed in both men and women. Then they reversed the process and had the computer estimate a person’s age based on brain metabolism data. The approach worked.

“It was highly predictive of age,” Goyal says.

Even so, for some people there was a big difference between their brain age and their chronological age. And Goyal says the team wondered whether this difference was more pronounced in men or women. So they verified.

“When we looked at males vs. females, we did find an effect,” Goyal says. “We found in fact that females had a younger brain age relative to males.”

Women’s brains appeared about four years younger, on average. But it’s still not clear why.

“It makes us wonder, are hormones involved in brain metabolism and how it ages?” Goyal says.

Or is it something else, like genetics? Whatever the cause, higher metabolism may give female brains an edge when it comes to learning and creativity in later life, Goyal says.

“But it might also set up the brain for certain vulnerabilities,” he says, including a higher risk of developing Alzheimer’s disease.

Brinton sees it differently. She thinks women’s higher brain metabolism protects them from Alzheimer’s when they are young.

But menopause, she says, causes an “energy transition in the brain,” one that affects the brain metabolism of some women far more than others. Brinton’s research suggests that the women most likely to experience a dramatic drop are those who carry a gene variant called APOE4, which increases a person’s risk of developing Alzheimer’s, or those who have risk factors for Type 2 diabetes.

“It’s those women who will begin to develop the pathology of Alzheimer’s disease earlier,” she says.

As brain metabolism decreases in these women, Brinton says, there’s an increase in the sticky proteins that are associated with Alzheimer’s.

“This is a process that starts very early in the aging process for some women,” Brinton says. “And we can intervene.”

How? The steps are a lot like those intended to prevent diabetes, Brinton says. They include diet, exercise and drugs that help the brain and body metabolize sugar.

Additional evidence of a link between menopause and Alzheimer’s

As pharma companies struggle with developing a treatment for Alzheimer’s disease, researchers continue to find evidence that links the dreaded form of dementia to other medical and health issues. The latest news suggests a potential link between Alzheimer’s and menopause.

The Wall Street Journal reported that researchers are beginning to examine whether or not hormonal changes related menopause contribute to the development of Alzheimer’s. About two-thirds of the people diagnosed with Alzheimer’s are women. Lisa Mosconi, director of the Weill Cornell Women’s Brain Initiative in New York City, a research program aimed at reducing Alzheimer’s risk, told the Journal that menopause does have some effect on the brain.

BioSpace says that according to the report, menopause affects the brain in various ways, including hot flashes, night sweats and memory changes. These symptoms are caused by declining levels of estrogen. It is estrogen that protects women’s brain from aging and stimulates neural activity, Mosconi told the Journal.

According to the article, “Studies show that when estrogen production declines during menopause, the brain’s metabolism appears to slow down and it becomes less efficient.”

Additionally, the Journal said that estrogen could help prevent the buildup of tau proteins and amyloid plaques that many researchers have linked to Alzheimer’s disease.

During menopause, Mosconi said that women’s brains tend to age faster than men’s, which is likely related to the loss of estrogen. Mosconi was careful to note that menopause does not cause Alzheimer’s, but could accelerate the process in women who may be predisposed to the disease. Now, there is a question if post-menopausal women who undergo hormone therapy will help prevent Alzheimer’s, or if it will put women at risk, the Journal said.

More research into this idea is needed and Mosconi has funding to look at hormonal and brain changes in both men and women at risk of developing Alzheimer’s disease, the Journal reported.

Estrogen and menopause are just two of the latest ideas surrounding the onset of Alzheimer’s in some patients. In January, BioSpace reported a potential link between Alzheimer’s and gum disease. Studies have described a link between Porphyromonas gingivalis (Pg), a bacteria that causes gingivitis, or chronic gum disease, and Alzheimer’s disease.

Researchers with the biopharma company Cortexyme Inc. (San Francisco) published a study that showed evidence of Pg in the brain of Alzheimer’s patients. Additionally, in mouse models, the company noted that oral Pg infection led to brain colonization. That led to an increase in the production of amyloid beta, which is the protein closely associated with Alzheimer’s.

Also, the Cortexyme researchers identified gingipains, the Pg’s toxic proteases, in the neurons of Alzheimer’s patients. As a result, the company designed a series of small molecule drugs that targeted Pg gingipains in hopes of showing efficacy in Alzheimer’s patients.

Sleep issues could also be associated with Alzheimer’s disease.

Last fall, a study suggested an association between sleep problems and Alzheimer’s disease.

As BioSpace reported at the time, the study found that, “People who reported shorter sleep duration and poorer sleep quality had greater beta-amyloid deposits.” Older adults who felt tired during the day, beyond the simple desire to take a nap, “were three times more likely to have beta-amyloid accumulation in their brains.”

Steve’s Take:

What’s the sixty-four-dollar question all these years later? It’s “Why is Alzheimer’s far more likely in women?”

Sure, as pointed out earlier in this piece, women’s brains age several years more slowly than men’s. Most of us men realize this but don’t speak about it, nor worry much about it. (I said, “most.”) But now it’s no secret that women are far more likely to develop Alzheimer’s disease. Researchers previously attributed this to the longevity of women, but scientists are finding that there may be other contributing factors to the disease.

While Alzheimer’s is indiscriminate, says Alzheimer’s.net, recent studies have found that women are bearing a disproportionate amount of the Alzheimer’s burden:

1) Aside from the fact that 60% of all Alzheimer’s caregivers are women, at the age of 65, women have a 1 in 6 chance of developing Alzheimer’s, compared to a 1 in 11 chance for men;

2) Additionally, out of the 5 million people living with Alzheimer’s in the US, 3.2 million are women; and

3) Research has found that women in their 60s are twice as likely to develop Alzheimer’s than to develop breast cancer.

Maria Carrillo, chief science officer for the Alzheimer’s Association, said of these risks:

“There are enough biological questions pointing to increased risk in women that we need to delve into that and find out why. There is a lot that is not understood and not known. It’s time we did something about it.”

Risk factors beyond longevity

Until now, the gap between women and men with AD had been largely attributed to the longevity of women, since age is the number one risk factor for Alzheimer’s. On average, women live four or five years longer than men and we know that Alzheimer’s is a disease that starts 20 years before the diagnosis.

Thus far, genetic studies have offered a startling account for the difference. Researchers from Stanford University studied over 8,000 people looking for a form of the gene ApoE-4, a gene that increases the risk of Alzheimer’s. They found that women who carry a copy of that particular gene variant were twice as likely to eventually develop Alzheimer’s as women without the gene. Men who had the gene were only at a slightly increased risk than men who did not have the gene. While it is not clear why the gene poses such a drastic increase in risk, KOLs believe it may be how the gene interacts with estrogen.

Another study suggests that it may be related to heart health. A study from Framingham, Massachusetts suggests that because men are more likely to die from heart disease in middle age, those men who live past 65 may have healthier hearts which may protect the brain from Alzheimer’s. These two diseases share many risk factors including high cholesterol, diabetes and obesity.

Bottom Line:

Exactly why women are bearing the Alzheimer’s burden still remains yet to be determined definitely. Carrillo pointed out that 40 years ago, no one really understood how heart disease affected women and says: “How do we make sure we’re not making that mistake when it comes to Alzheimer’s?”

That’s my sixty-four-dollar question. And thankfully, these latest studies examining the metabolism of the aging female brain are discovering the how’s and why’s of that very process. That should point to the most fruitful paths science might pursue to foster the beneficial characteristics of the process and prevent or slow the progress of mild cognitive impairment- to dementia- to AD. It’s time to accelerate the evolution of the science, now that we have some excellent, concrete data with which to work.

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