— Midlife, early-life risk factors now more common, differ by sex, race/ethnicity

by Judy George, Senior Staff Writer, MedPage Today May 9, 2022

Eight modifiable risk factors were linked to more than one in three cases of Alzheimer’s disease and related dementia in the U.S., a cross-sectional analysis showed.

The eight risk factors — midlife obesity, midlife hypertension, physical inactivity, depression, smoking, low education, diabetes, and hearing loss — were associated with 36.9% (95% CI 36.5-37.3) of Alzheimer’s and dementia cases, reported Roch Nianogo, MD, PhD, of the University of California Los Angeles, and Deborah Barnes, PhD, MPH, of the University of California San Francisco, and co-authors.

Of note, risk factors differed based on sex, race, and ethnicity, they wrote in JAMA Neurology.

The factors most prominently associated with Alzheimer’s and dementia were midlife obesity, at 17.7% (95% CI 17.5-18.0); physical inactivity, at 11.8% (95% CI 11.7-11.9); and low educational attainment, at 11.7% (95% CI 11.5-12.0).

“We published a similar study a little more than 10 years ago, and the most important risk factors then were physical inactivity, depression, and smoking,” Barnes told MedPage Today.

“Today, the top three risk factors are midlife obesity, physical inactivity, and low education,” she observed. “This is important because it suggests that the growing number of people who are obese in the U.S. could have a major long-term impact on dementia rates.”

“Our results also highlight the importance of making sure everyone in our country gets adequate education,” Barnes added. “COVID-19 had a devastating impact on education and graduation rates and it will be important to help those students get caught up. This is especially true in Hispanic individuals, where low education is the biggest risk factor.”

Because there’s no effective cure for Alzheimer’s and dementia, prevention is very important, emphasized Nianogo. Risk reduction strategies may be more effective if they target higher-prevalence risk factors, he suggested.

“Understanding which risk factor plays a role in accelerating cognitive decline can help providers and individuals be proactive in addressing these risk factors early in their lifetime,” Nianogo told MedPage Today. “We also wanted to understand what that meant for different subpopulations defined by sex and race and ethnicity, as this can be important for designing tailored and targeted interventions.”

Almost two-thirds of people with Alzheimer’s and dementia in the U.S. are women. Compared with white older adults, Black older adults are twice as likely to develop Alzheimer’s and dementia, and Hispanic older adults are 1.5 times as likely.

Risk reduction could also provide an important public health and prevention opportunity to help address the projected increase in dementia prevalence, Nianogo and Barnes noted.

For this study, the researchers gathered risk factor prevalence information from 378,615 participants in the 2018 CDC Behavioral Risk Factor Surveillance System and extracted relative risks for each factor from recent meta-analyses.

In the study sample, 171,161 people (weighted 48.7%) were men and 134,693 people (weighted 21.1%) were 65 and older. Self-reported race and ethnicity data showed that 6,671 participants (weighted 0.9%) were American Indian and Alaska Native; 8,043 (weighted 5.1%) were Asian; 29,956 (weighted 11.7%) were Black; 28,042 (weighted 16.0%) were Hispanic; and 294,394 (weighted 64.3%) were white.

For each of the eight modifiable risk factors, the population-attributable risk was:

• Hearing loss: 2.3%
• Current smoking: 6.0%
• Diabetes: 7.3%
• Depression: 8.5%
• Midlife hypertension: 8.8%
• Low education: 11.7%
• Physical inactivity: 11.8%
• Midlife obesity: 17.7%

Midlife hypertension and midlife obesity were the most prevalent risk factors among all participants, but prevalence varied by race and ethnicity. Midlife obesity was more prevalent in American Indian and Alaska Native, Black, and Hispanic populations; low education was more prevalent among Hispanic individuals.

Associations with Alzheimer’s and dementia risk also differed by race and ethnicity. Among Black (21.7%), American Indian and Alaska Native (20.3%), and white (17.3%) populations, midlife obesity showed the strongest association with Alzheimer’s and dementia. Among Hispanic individuals, low educational attainment had the strongest tie (26.5%), while in Asian participants, physical inactivity topped the list (9.5%).

Combined population-attributable risks were higher in men (35.9%) than in women (30.1%). Risk associated with depression was higher in women (10.5%) than in men (6.4%).

The findings suggest the most prominently modifiable risk factors associated with Alzheimer’s and dementia have changed over the past decade and differ based on sex, race, and ethnicity, the researchers said.

“It’s important to note that these findings were mostly based on observational studies,” Nianogo pointed out.

“While they could reflect what is really happening, they could also reflect the effect of other factors not accounted for in our study,” he acknowledged. “More rigorous study designs are needed to shed more light on this important issue.”