US POINTER Study Results: A Structured Lifestyle Intervention Improved Cognition in Older Adults

Findings from the US POINTER clinical trial (NCT03688126) were presented at the 2025 meeting of the Alzheimer’s Association International Conference (AAIC), demonstrating significant benefits linked to lifestyle interventions for older adults at risk of cognitive decline and dementia. According to the study results, in terms of global cognition over 2 years, a lifestyle intervention that was more structured and higher in intensity conveyed greater benefits for this patient population compared with an unstructured, self-guided intervention.

US POINTER was a single-blind, randomized, multicenter study that included 2111 participants aged 60 to 79 years with a sedentary lifestyle and suboptimal diet plus at least 2 additional risk criteria related to family history of memory impairment, cardiometabolic risk, race and ethnicity, older age, and sex. Participants were randomized 1:1 to structured or self-guided interventions at 5 sites in the United States between May 2019 and March 2023 and were followed for 2 years. Both study groups emphasized increased physical and cognitive activity, dietary improvements, social engagement, and cardiovascular health monitoring, but the structured intervention program featured more oversight, accountability, and engagement. Eighty-nine percent of the participants completed the assessment at year 2.

Key Findings:

• Both groups improved on a composite measure of global cognition, but the structured intervention group demonstrated a significantly higher rate of annual improvement from baseline (increase of 0.243 standard deviations [SD] per year; 95% CI, 0.227 to 0.258) compared with the self-guided intervention group (increase of 0.213 SD per year; 95% CI, 0.198 to 0.229).
• The structured intervention group had a significantly greater mean rate of increase per year from baseline (0.029 SD per year; 95% CI, 0.008 to 0.050; P=.008) compared with the self-guided intervention group.
• Benefits of the structured intervention group were consistent among participants with and without the APOE ε4 allele (P=.95 for interaction), but these benefits were greater for adults with lower vs higher baseline cognition (P=.02 for interaction)
• Fewer adverse events were reported in the structured intervention group (151 serious, 1091 nonserious) compared with the self-guided intervention group (190 serious, 1225 nonserious); COVID-19 positivity was the most common event overall and occurred more frequently in the structured intervention group.