A new meta-analysis corrects previous knowledge on sex-specific risk of developing Alzheimer's disease. After analyzing data from almost 58,000 individuals of both sexes, the researchers suggest that women are more at risk than men during a crucial 10-year span: between ages 65 and 75.

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New meta-analysis finds that women have the same risk of Alzheimer's as men throughout their total lifespan. However, they are significantly more at risk from their mid-60s to their mid-70s.

According to an influential study published in JAMA 20 years ago, one gene variation of the apolipoprotein E (APOE) gene, E4, placed women at a great risk of developing Alzheimer's disease (AD) than men. This belief has influenced the way in which specialists understood AD risk factors until now.

A new meta-analysis that re-evaluates data and evidence suggests that things may not be as clear-cut as it has been thought so far.

The study - conducted by Dr. Scott C. Neu from the Keck School of Medicine at the University of Southern California in Los Angeles, CA, alongside a team of specialists from many institutions - suggests that women and men carrying the E4 variation of the APOE gene are at a similar risk of developing AD.

However, there is one important exception to that rule: women are significantly more susceptible to AD between the ages of 65 and 75, which had not been known until now.

The researchers' findings were recently published in JAMA Neurology.

65 to 75: a critical decade for women

The team of researchers analyzed 27 independent research studies, collecting data from 57,979 individuals from North America and Europe. The complex data were provided by the Global Alzheimer's Association Interactive Network (GAAIN).

GAAIN is an important resource that allows researchers to access and analyze data from people diagnosed with AD all over the world. The wealth of information now placed within the reach of specialists has allowed the team conducting the current study to update crucial information about AD.

"We were surprised that so much work over the last 20 years has been dependent upon one 1997 study [...] Using a new big data platform, the [GAAIN], we saw that we had nine times the data of the 1997 study and decided to take a second look," study co-author Dr. Arthur W. Toga, from the Keck School of Medicine, told Medical News Today.

After analyzing the data available to them, the researchers concluded that there was no "difference in risk of Alzheimer's disease across the lifespan of 55 to 85 years" between men and women carrying a copy of the E4 variant of the APOE gene. Yet "women were at increased risk [compared to] men between ages 65 and 75."

Some existing studies linked risk of AD and cognitive decline with menopause, as well as genetic factors, but current findings show that the critical period when women are most at risk is 10 years after the normal start of menopause.

Dr. Toga explained for MNT that these conclusions indicate that specialists may want to assess women for AD risk factors at the age when they are most susceptible to the disease.

"[P]hysiologic changes associated with menopause and estrogen loss, which on average begin at 51 years of age, may play a role with the APOE [gene variation] in increasing women's risks for [AD], which suggests that researchers could study women around this time period for any detectable signals that suggest increased risk for Alzheimer's."

Dr. Arthur Toga

Still, Dr. Judy Pa, co-author of the study, also from the Keck School of Medicine, says that women should not rely on genetic testing to learn whether or not they will develop AD. Exhibiting one or more risk factors, she explains, does not necessarily mean that an individual will develop the disease.

"There is controversy in terms of whether people should know their APOE status because it is just a risk factor," she says. "It doesn't mean you're going to get Alzheimer's disease. Even if you carry two copies of [the gene variant], your chances are greatly increased, but you could still live a long life and never have symptoms."

According to Dr. Pa, women who are at an increased risk of AD may be able to keep its development in check by leading an active life and exercising their cognition.

"Get more exercise. Work out your mind, especially in old age. Pick up hobbies that are cognitively or physically challenging. Reduce processed sugar intake because it's linked to obesity, which is associated with many chronic diseases," she encourages.

More focus on women and minorities

The specialist also emphasizes the importance of focusing more studies on women, specifically, in the light of her and her colleagues' recent findings. Potential differences in susceptibility to diseases that are owed to biological distinctions between women and men must be studied further and understood better.

"The bottom line is women are not little men. A lot more research needs to target women because gender-specific variations can be so subtle that scientists often miss them when they control for gender or use models to rule out gender differences. Most research today is ignoring a big part of the equation," claims Dr. Pa.

Some significant obstacles and limitations were also acknowledged by the researchers. The data they obtained came mostly from white individuals, and very few people belonging to minority groups were involved in the initial studies.

This led the researchers to focus their attention on the white population only, although they admit that this situation is far from ideal. The scientists would like to see their results replicated in more racially and ethnically diverse groups, which are currently underrepresented in research of this kind.

"Most of the archives around the world have insufficient numbers of underrepresented groups. One of the take-home messages from our study is [that] people of all races and ethnicities need to be involved in Alzheimer's clinical trials because this disease is a problem that affects all of us," says Dr. Toga.