Structured lifestyle program improves cognition in at-risk older adults

The Alzheimer’s Association U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) found that certain lifestyle interventions improved cognition in older adults at risk of cognitive decline. U.S. POINTER is a two-year, multi-site clinical trial, one of which is the Baylor College of Medicine’s Alzheimer’s Disease and Movement Disorder Center, testing two different lifestyle interventions in a representative population of older adults at risk for cognitive decline and dementia.

Trial participants in the structured (STR) intervention showed greater improvement on global cognition compared to the self-guided (SG) intervention, protecting cognition from normal age-related decline for up to two years. The STR intervention differed from the SG intervention in intensity, structure, accountability and support provided.

The results were reported for the first time today at the Alzheimer’s Association International Conference (AAIC 2025) in Toronto and online. “Effects Of Structured vs. Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function: The U.S. POINTER Randomized Clinical Trial,” was published in JAMA simultaneously.

U.S. POINTER is the first large-scale, randomized controlled clinical trial to demonstrate that an accessible and sustainable healthy lifestyle intervention can protect cognitive function in diverse populations in communities across the United States.

“This study demonstrates that there are actions we can all take to improve our cognition as we age and provides a model for implementation of future, larger-scale interventions. I want to thank our POINTER participants as well as the Baylor, Kelsey and Alzheimer’s Association teams for their great work on this important study,” said Dr. Melissa Yu, professor of neurology and director of the Alzheimer’s disease and Memory Disorders Center at Baylor.

“As the burden of dementia grows worldwide, U.S. POINTER affirms a vital public health message: healthy behavior has a powerful impact on brain health,” said Dr. Joanne Pike, Alzheimer’s Association president and CEO.

“This is a critical public health opportunity. The intervention was effective across a broad, representative group—regardless of sex, ethnicity, APOE genetic risk, or heart health status—demonstrating its applicability and scalability for communities across the country,” said Pike. “The positive results of U.S. POINTER encourage us to look at the potential for a combination of a lifestyle program and drug treatment as the next frontier in our fight against cognitive decline and possibly dementia.”

U.S. POINTER leadership acknowledges participants, their family members and study site staff for their unique and essential contributions: “You helped change what we know about brain health. Thanks to your dedication, time and support, U.S. POINTER delivered groundbreaking results. Your children, grandchildren and generations to come will benefit from the commitment you made.”

Both interventions focused on physical exercise, nutrition, cognitive challenge and social engagement, and heart health monitoring, but differed in intensity, structure, accountability and support provided.

In the structured lifestyle intervention, participants attended 38 facilitated peer team meetings over two years, and were provided with a prescribed activity program with measurable goals for: aerobic, resistance and stretching exercise; adherence to the MIND diet; cognitive challenge through BrainHQ training and other intellectual and social activities; and regular review of health metrics and goal-setting with a study clinician.

In the self-guided lifestyle intervention, participants attended six peer team meetings to encourage self-selected lifestyle changes that best fit their needs and schedules. Study staff provided general encouragement without goal-directed coaching.

“This was a landmark study showing that changes in diet, physical activity and mental and social engagement can result in significant, measurable cognitive benefits in a very short period of time. We hope the results will encourage health care providers to recommend the lifestyle changes tested in the POINTER trial,” said Dr. Valory Pavlik, professor of neurology at Baylor.

“The potential to improve cognition with fewer resources and lower participant burden is compelling. It highlights that while not everyone has the same access or ability to adhere to more intensive behavior interventions, even modest changes may protect the brain,” said Dr. Laura D. Baker, professor of gerontology and geriatrics, and internal medicine, at Wake Forest University School of Medicine and Advocate Health, and U.S. POINTER principal investigator.

“These are the initial results. Over the coming weeks and months, study leadership will be exploring all of the data collected in the trial to paint an even more comprehensive picture of the U.S. POINTER intervention effects on brain health,” Baker said.

People with cognitive decline and dementia often have a variety of damaging changes in their brain. This means effective treatment will likely require a multi-pronged or combination strategy to address multiple disease mechanisms.

“Complex diseases like heart disease and cancer use combination treatment strategies tailored to individual characteristics. The next generation of treatments for diseases like Alzheimer’s will likely integrate drug and non-drug strategies. U.S. POINTER provides a strong foundation for such combination approaches,” said Dr. Heather M. Snyder, Alzheimer’s Association study primary investigator and senior vice president of medical and scientific relations.

“While these results are fascinating and extremely hopeful, how they are rolled out to the public—especially those at risk for Alzheimer’s and other diseases that cause dementia—needs to be handled with care and individual attention tailored to the local environment,” said Snyder.

The Alzheimer’s Association has invested nearly $50 million to lead this study to date, with additional support from the National Institute on Aging at the National Institutes of Health for add-on studies exploring imaging, vascular measures, sleep and gut microbiome-related health data. In addition to its investments to date, the Alzheimer’s Association will invest more than $40 million over the next four years to continue to follow U.S. POINTER participants, and to bring U.S. POINTER interventions to communities across America.

“It was an honor for the research team in the Alzheimer’s Disease and Memory Disorders Center in the Department of Neurology to have the opportunity to serve as one of the U.S. POINTER study sites. We want to thank our partners from the Kelsey Research Foundation for their essential contributions in implementing the U.S. POINTER intervention,” Pavlik said.

U.S. POINTER is a phase 3, five-site, two-year, single-blind randomized clinical trial of two lifestyle interventions in older adults at risk for dementia. U.S. POINTER was developed to assess whether the results of the FINGER study [Lancet, 6-6-15] generalize to a larger, more diverse U.S. population at risk for cognitive decline and dementia, using culturally adapted protocols.

The primary aim was to compare the effects of two multimodal lifestyle interventions on global cognitive function in 2,000+ at-risk older adults. Secondary aims assessed intervention effects on specific cognitive domains, and potential differences based on baseline cognition, sex, age, APOE-e4 genotype, and cardiovascular risk.

The study was conducted at five geographically dispersed U.S. academic centers and health care systems in partnership with the Alzheimer’s Association. Participant eligibility criteria were designed to enrich the risk of cognitive decline and included older age (60–79 years), sedentary lifestyle, suboptimal diet and cardiometabolic health, and family history of memory impairment.

A total of 2,111 participants were enrolled and randomized to STR (n=1,056) or SG (n=1,055). Mean age was 68.2 years, 68.9% were female, 30.8% were from ethnoracial minority groups; 78% (78%) reported a first-degree family history of memory loss, and 30% were APOE-e4 carriers. Retention was high, with 89% completing the final two-year assessment.

At two years, there was a statistically significant intervention group difference on the primary outcome. Global cognitive composite scores (primary outcome) increased over time in both groups but the improvement over time was statistically significant for a greater benefit for the STR versus SG: 0.029 SD per year (95% CI, 0.008–0.050, P=0.008).

For secondary outcomes, the increase in executive function z-score was greater in STR than SG by 0.037 SD per year (95% CI, 0.010–0.064). Processing speed showed a similar trend but was not statistically significant. There were no group differences in memory.

Looking ahead, the Association will build on the momentum of U.S. POINTER by launching several programs and initiatives, including:

• A personal brain health assessment tool
• A virtual brain health training program for health care providers
• A community recognition program for organizations championing brain health
• A brain health roundtable that will unite leaders across health care, public health, community and corporate sectors to accelerate impact