Personalized Approach to Alzheimer’s Risk Factors Boosts Cognition

SAN FRANCISCO — A multidomain intervention that includes counseling by health coaches is associated with “modest” improvements in cognition in older adults who have at least two Alzheimer’s disease (AD) risk factors, results of a new pilot study suggest.

However, the control group in the National Institute on Aging (NIH)–funded SMAART study, which only received educational materials by mail, also showed improvements.

The findings suggest that “maybe this personalized approach was helpful. The effect size wasn’t huge, but it was larger than most multidomain trials,” study investigator Kristine Yaffe, MD, University of California, San Francisco, said in a presentation here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) Conference.

Personalized Approach

The investigators launched the SMAART trial in light of research suggesting that 30% to 40% of AD risk may be preventable. Modifiable risk factors for vascular-related conditions include hypertension, low physical activity, depression, and others, Yaffe said. However, some multidomain trials “have not been positive,” she added.

The new trial assessed a more personalized approach, she noted. “If you could get people to buy in, make the approach more pragmatic and personal to them, maybe you could actually move the window a little bit,” Yaffe said.

Researchers recruited 172 participants aged 70–89 years (average age, 75.7 years; 63% women; 81% non-Hispanic White) via the Kaiser Permanente health plan in Washington state.

All had at least two AD risk factors, such as poorly controlled hypertension or diabetes, social isolation, or current smoking status. Inactivity was the most common risk factor. Patients with dementia were excluded.

The 90 participants in the control group received educational materials from the Alzheimer’s Association every 3 months. The materials included information about reducing the risk for dementia. The other 82 participants chose one to three risk factors to focus on and worked with a trained health coach on goals. “Then we check in with them every 6 to 8 weeks or so” to determine whether the goals are being met, Yaffe noted.

The program worked with primary care physicians and focused on digital health resources, such as health apps and activity trackers.

A total of 149 participants finished the 2-year trial; 19 withdrew or were lost to follow-up, and four died.

The primary outcome was composite cognitive score. At 2 years, both groups improved in an adjusted intention-to-treat analysis: the intervention group by about 5 points, and the placebo group by nearly 3 points (average treatment effect, 0.15; sd, 0.04 – 0.26; P = .008).

“Compared to the control group and how much they changed, the intervention group got about 80% better,” Yaffe said.

Asked why the control group improved so much on its own, she told Medscape Medical News that an improvement in cognitively normal adults is common. In the current study, this could be due to a placebo effect or more familiarity with the cognitive tests, she noted.

Yaffe reported that no participants experienced study-related severe adverse effects and that participants in both arms reported that they enjoyed the study.

The presentation did not address the cost of the intervention.

Risk-Reduction Strategies

Commenting for Medscape Medical News, Heather M. Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said, “It is good to see this pilot study show a benefit by addressing known dementia risk factors. Approaches that use risk-reduction strategies are exciting.”

However, “we need larger studies with more diverse populations so that we can be confident that risk-reduction strategies are available to and benefit all individuals and communities,” Snyder said.

She added that the trial “adds to past work” that has shown that addressing risk factors such as diabetes, inadequate sleep, and lack of physical activity may benefit overall health, including cognition.

The study also “demonstrated the feasibility of conducting a lifestyle-based intervention like this through a large health system, suggesting a possible future where we identify individuals with increased risk and provide personalized risk reduction interventions, very much like we do now for heart disease,” Snyder said.

The Alzheimer’s Association has launched its own 2-year clinical trial, called the US Pointer Study, to evaluate the effect of lifestyle interventions in older adults at risk of cognitive decline. Results are expected to be published in 2025.

The study was funded by the National Institute on Aging. Yaffe serves on data and safety monitoring boards for the NIH, Eli Lilly, and the Dominantly Inherited Alzheimer Network trials and is on the board of directors for Alector. Snyder has reported no relevant financial relationships.

15th Clinical Trials on Alzheimer’s Disease (CTAD) Conference: Presented November 30, 2022.

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