Structured Lifestyle Program Yields Statistically Significant Cognitive Gains in US POINTER Trial

Laura Baker, PhD

Courtesy of Wake Forest University School of Medicine

A 2-year, phase 3 randomized clinical trial of more than 2111 sedentary adults aged 60 to 79 years at elevated risk for dementia found that both a structured, coach-supported lifestyle program and a lower-intensity self-guided approach improved global cognition, with the structured arm providing a modest but statistically significant additional benefit.¹

The US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (US POINTER) enrolled 2111 participants across 5 US academic centers; 68.9% were women and 30.8% identified with ethnoracial minority groups. Retention at 24 months was 89%.¹

Participants were randomized 1:1 to a structured (STR) or self-guided (SG) multidomain lifestyle intervention targeting physical activity, adherence to the MIND diet, cognitive and social stimulation, and cardiometabolic risk management. The STR arm met in facilitated peer teams 38 times over 24 months with prescriptive goals for aerobic, resistance, and flexibility exercise, BrainHQ cognitive training, and clinician-reviewed health metrics, whereas the SG arm met six times and relied on participant-selected behavior changes with general encouragement.¹

Primary and secondary outcomes. Global cognitive composite scores improved in both groups; the annualized gain favored STR over SG by 0.029 standard deviations (95 % CI, 0.008-0.050; P = .008). Executive function improved an additional 0.037 standard deviations per year in STR (95% CI, 0.010-0.064). Processing speed trended in the same direction, while memory scores did not differ between groups. Benefits were consistent regardless of age, sex, ethnicity, apolipoprotein E ε4 genotype, or baseline cardiovascular health.¹

“As the burden of dementia grows world-wide, U.S. POINTER affirms a vital public health message: healthy behavior has a powerful impact on brain health,” Joanne Pike, DrPH, president and chief executive officer of the Alzheimer’s Association, said in a press release.²

Lead investigator Laura D. Baker, PhD, noted that even the lower-intensity program was cognitively beneficial: “The potential to improve cognition with fewer resources and lower participant burden is compelling… even modest changes may protect the brain.”²

Researchers will continue to analyze vascular, imaging, sleep, and gut microbiome data collected during the study and explore combined pharmacologic and lifestyle strategies to further mitigate dementia risk.¹

References:

1. Kivipelto M, et al. Long-term adherence to lifestyle changes and association with cognitive change: Eleven-year results from the FINGER randomized, controlled trial. Presented at: Alzheimer’s Association International Conference; July 27-31, 2025; Toronto.
2. U.S. Pointer Study Shows Structured Lifestyle Program Targeting Multiple Risk Factors Improves Cognition in Older Adults at Risk of Cognitive Decline. News release. Alzheimer’s Association. July 28, 2025. Accessed August 4, 2025. https://aaic.alz.org/releases-2025/us-pointer-study-results-announced.asp