Intensive, Structured Lifestyle Program Boosts Cognition

Two different lifestyle interventions improved cognition over 2 years in older adults at risk for cognitive decline, topline results from the Alzheimer’s Association’s US POINTER study showed. 

However, the high-intensity, structured intervention with more support and accountability led to significantly greater improvement on global cognition compared to a less intense, self-guided intervention.

“Compared to the self-guided group, participants in the structured group performed at a level comparable to adults 1 to 2 years younger in age” — an effect that is “predicted to increase resilience against cognitive decline in the future,” principal investigator Laura Baker, PhD, professor of gerontology, geriatrics, and internal medicine at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said during a press briefing. 

At the same time, the potential to improve cognition with fewer resources and lower participant burden is “compelling [and] 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,” Baker added in a news release from the Alzheimer’s Association.

The results were presented July 28 at the Alzheimer’s Association International Conference (AAIC) 2025 and simultaneously published in JAMA. 

First Large-Scale Clinical Trial 

US POINTER is the first large-scale randomized controlled clinical trial in the US to explore the impact of comprehensive lifestyle changes on cognitive health in older adults at risk for cognitive decline and dementia.

Participants included 2111 adults aged 60-79 years who were sedentary and had a suboptimal diet and at least two other risk factors associated with late-life cognitive decline, including family history of memory impairment, elevated cardiometabolic risk, minority race, and male sex. 

They were randomly allocated in a 1:1 ratio to receive a structured or self-guided intervention. Both interventions encouraged increased physical and cognitive activity, healthy diet, social engagement, and cardiovascular health monitoring, but they differed in structure, intensity, and accountability. 

The structured intervention included 38 facilitated peer team meetings over 2 years; a prescribed activity program with measurable goals for aerobic, resistance, and stretching exercise; adherence to the MIND diet; computerized brain training and other intellectual and social activities; and regular review of health metrics and goal setting with a study clinician.

The self-guided intervention also received support, but not on the scale of the structured intervention. They attended six peer team meetings over 2 years and chose lifestyle changes that would best suit their needs and schedules. Study staff provided general encouragement without goal-directed coaching. 

The high adherence to both interventions was notable, the researchers said, with less than 4% discontinuing the intervention in either group; 89% of individuals completed all assessments over the 2 years. 

The primary comparison was the difference between intervention groups in annual rate of change in global cognitive function, assessed by a composite measure of executive function, episodic memory, and processing speed, over 2 years. 

After 2 years, both groups showed cognitive improvements compared to baseline on this primary outcome measure. The structured and self-guided groups improved on average by 0.243 SD and 0.213 SD, respectively. However, the average rate of increase per year was statistically significantly greater for the structured group than the self-guided group by 0.029 SD (P = .008). 

The additional benefit of 0.029 SD per year for the structured intervention closely aligns with the protocol target of 0.030 SD per year. This was based on the effect size reported in the FINGER trial, which also demonstrated cognitive benefits with a similar multidomain lifestyle intervention. 

The benefits of the lifestyle interventions in US POINTER were consistent across age, sex, ethnicity, heart health, and APOE4 gene status.

“Cognitive benefits did not differ between APOE ε4 carriers and noncarriers, “suggesting that lifestyle interventions may be effective even among individuals at elevated cardiovascular or genetic risk of dementia,” the researchers wrote. 

“Future analyses of POINTER data, including additional cognitive measures, functional outcomes, fluid and imaging biomarkers, and longer-term cognitive trajectories, may help clarify the clinical significance and durability of these findings,” they noted. 

In addition to its nearly $50 million investments to date in US POINTER, the Alzheimer’s Association said it will invest more than $40 million over the next 4 years to continue to follow study participants and start to bring these interventions to communities across the US.

“The science of implementation is going to be very important,” Maria Carrillo, PhD, chief science officer and medical affairs lead, Alzheimer’s Association, told the briefing. To start, the association plans to partner with 10 communities across the country in order to test the ability to implement the US POINTER interventions, she explained. 

In a statement on the US POINTER topline results, Howard Fillit, MD, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said that “the future lies in precision prevention. We have seen this model succeed in cancer and heart disease, and with a growing body of evidence showing neither lifestyle nor drugs can stop Alzheimer’s alone, now is the time to double down on studying the two in combination, which will lay the path for precision medicine.”

Caveats, Cautionary Notes 

The author of an accompanying editorial also published in JAMA on the US POINTER study said that interpreting the US POINTER study results requires “nuance.”

Although the structured intervention yielded a statistically significant edge, the clinical relevance of this difference — roughly a 14% relative benefit — is “uncertain” and “the more striking finding is perhaps the similarity of the cognitive benefits across both groups, despite the self-guided group requiring only a fraction of the engagement and interventions,” wrote Jonathan Schott, MD, with the Dementia Research Center, University College London, London, United Kingdom.

“From a pragmatic clinical and public health perspective, the key message of US POINTER may be that even relatively modest lifestyle changes can support cognitive health in aging populations. The challenge ahead will be to determine how best to implement such programs widely, equitably, and effectively — and whether their benefits are maintained over time and translate into clinically meaningful end points,” Schott added. 

Schott also noted that existing public health measures to combat cognitive decline may already be having an impact. 

“[A]ge-specific declines in the incidence of dementia in the US and other high-income countries have been observed in recent years and may relate in part to improved education and management of cardiovascular risk within these populations in the preceding decades,” he pointed out. 

This study was supported by the Alzheimer’s Association. Baker, Schott, and Fillit report no disclosures.