After age and genetics, being a woman is the single most important risk factor for developing Alzheimer's disease, experts say.

"Two out of every three brains affected by Alzheimer's disease are women's brains," said Dr. Richard Isaacson, director of the Alzheimer's Prevention Clinic in the Center for Brain Health at Florida Atlantic University's Schmidt College of Medicine.

Now, a new study has good news when it comes to giving women a chance to reduce their increased risk. Personalized lifestyle interventions -- such as diet, exercise, stress reduction and sleep hygiene -- were able to reduce Alzheimer's risk factors in both sexes, but they worked even better in women.

"Our individually tailored interventions led to greater improvements in women compared to men across risk scales for Alzheimer's and cardiovascular disease," said Isaacson, who coauthored the paper.

Women also showed greater improvements than men in biomarkers such as lower blood sugar and lower LDL, or low-density lipoprotein, which is the "bad" cholesterol.

"This study clearly reinforces the need for additional larger studies to be able to better predict the baseline cognitive trajectory in aging females versus males," said Rudy Tanzi, a professor of neurology at Harvard Medical School. He is director of the genetics and aging research unit at Massachusetts General Hospital in Boston.

"As we aim to find ways to nip this disease in the bud stage, we will need to know if prevention and treatment strategies will work equivalently on both men and women. This new study clearly brings us a big step closer to that goal," said Tanzi, who was not involved in the study.

The new study followed a subset of people participating in a 10-year study designed to test the impact of personalized recommendations on cognitive function and risk factors for dementia. The Comparative Effectiveness Dementia and Alzheimer's Registry trial, which began in 2018, is being conducted at NewYork-Presbyterian/Weill Cornell Medical Center in New York City.

After full blood, physical, cognitive and genetic workups, patients were provided with individualized genetic counseling and education. Medications, vitamins and supplements were tailored to each person's unique results as well. In addition, all participants received personalized lifestyle interventions, such as counseling on exercise, diet, blood pressure control, sleep hygiene and stress reduction.

Everyone in the CEDAR trial has a family history of Alzheimer's, but the majority had no signs of cognitive decline when the study began, Isaacson said. Of the 154 men and women participating in the research, 35 were diagnosed with mild cognitive impairment, or MCI, due to Alzheimer's, but it was not severe enough to "impact their daily lives," he said.

The original study's main findings were published in 2019. People with MCI saw their performance on cognitive tests for memory and thinking skills improve by nearly 5 points when they followed at least 60% of their lifestyle recommendations (on average, at least 12 of the 21 different recommendations) for 18 months.

However, the 2019 study found that people with mild cognitive impairment who followed less than 60% of the suggestions showed no cognitive improvement -- in fact, they continued to decline by 6 points on average.

The cognitively normal patients with a family history of Alzheimer's disease, called the prevention group, were able to get an "equally impressive" cognitive boost of an average of 4.5 points by following at least some of the lifestyle recommendations. It didn't seem to matter if they followed less than 60% of them, Isaacson said.

"The good news from our study is that there were actually cognitive improvements at 18 months in both women and men when compared to the control populations," Isaacson said. "A lot of the drugs that have been studied aim to delay cognitive decline, but it is harder to show improved cognition over time."

Approximately half of the participants in CEDAR carry at least one APOE gene, which may increase the risk of developing Alzheimer's disease. However, the study found no difference in the intervention's cognitive benefits for those with one or two copies of APOE compared with those without the gene, "so that was also reassuring," Isaacson said.

The new study, published Tuesday in the journal of the Prevention of Alzheimer's Disease, took the original 2019 study a step further by analyzing a subset of participants to see whether there was any difference between men and women when it came to how well the lifestyle interventions work.

"Women have very different and unique risk factors than men for dementia," Isaacson said. "Women have a 39% higher risk of dementia if they have fat accumulating around their midsection.

"And the rapid decline in estrogen during the perimenopause transition can actually be one of the most impactful risk factors for developing Alzheimer's pathology in the brain," he said.

In the new analysis, women in the prevention group, who started the trial with no cognitive issues, demonstrated greater improvements than men in two areas: one of two cardiovascular risk scales and in levels of the good cholesterol, HDL, or high-density lipoprotein, which is protective against heart disease.

Women with mild cognitive decline, called the early treatment group, showed greater improvements than men when it came to average blood sugar levels and two cardiovascular risk scales. This female cohort also had more significant improvements in several important cholesterol (or lipid) biomarkers than men in the early treatment group.

For all participants, complying with an additional 10% of the personalized recommendations resulted in an additional 0.9 point improvement for women and 0.41 points of improvement for men on tests of cognition.

How does reducing cardiovascular risk impact future cognition? Because what's good for the heart is good for the brain, experts say.

"Vascular risk factors such as high blood pressure, high cholesterol, high blood sugar or diabetes may not be the cause of Alzheimer's disease, but it can fast-forward Alzheimer's pathology," Isaacson said. "I would prefer to slam on the brakes rather than rev the engine on the path to cognitive decline."

Finding that women were able to reduce their risk even more than men is welcome news, Isaacson said, as it provides a promising area for future study and gives hope that women can tip the battle against Alzheimer's in their favor.

"By treating people in an evidence-based yet safe way, using multiple lifestyle and medical interventions, we've shown that you can really make an impact on brain health," he said.

The-CNN-Wire

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