Structured lifestyle intervention improved global cognition in at-risk older adults, trial finds

A structured lifestyle intervention that included regular physical exercise, adherence to the MIND diet, cognitive challenge and social engagement, and cardiovascular health monitoring had a significantly greater benefit on global cognition over two years compared with an unstructured, self-guided intervention, according to results of a randomized controlled trial.

Participants in the U.S. study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (POINTER) trial were randomized to structured (n=1,056) or self-guided (n=1,055) interventions between May 2019 and March 2023 and completed final follow-up in May 2025. Both interventions encouraged increased physical and cognitive activity, healthy diet, social engagement, and cardiovascular health monitoring but differed in structure, intensity, and accountability. The structured group attended 38 team meetings over the course of the study with navigators and interventionists and received activity plans with quantifiable adherence metrics. The self-directed group attended six meetings over two years and did not get goal-directed coaching. All participants were ages 60 to 79 years and had a sedentary lifestyle and suboptimal diet at baseline, plus met at least two additional risk criteria. The study was carried out across five clinical sites. Findings were published by JAMA on July 28.

Eighty-nine percent of the 2,111 enrolled participants (mean age, 68.2 years; 68.9% female) completed the two-year assessment. The average global cognitive composite z score, constructed from equally weighted composites of executive function, episodic memory, and processing speed domains, increased from baseline over time in both groups. The mean rate of increase per year was 0.243 SD (95% CI, 0.227 to 0.258) for the structured intervention and 0.213 SD (95% CI, 0.198 to 0.229) for the self-guided intervention and was 0.029 SD greater for the structured versus the self-guided group (95% CI, 0.008 to 0.050; P=0.008).

Subgroup comparisons showed that the benefit from the structured intervention was consistent in carriers of APOE gene mutations and in noncarriers (P=0.95 for interaction) but appeared greater for adults with lower baseline cognition (P=0.02 for interaction). The structured group had fewer reported serious and nonserious adverse events (151 and 1,091, respectively) versus the self-guided group (190 and 1,225, respectively). COVID-19, the most common adverse event, occurred more frequently in the structured group.

Limitations include that the study was only conducted at five sites, potentially limiting generalizability, and that the trial was not powered to assess cognitive impairment or dementia outcomes.

An accompanying editorial highlighted the finding that most of the benefit came from improvements in executive function and noted that the clinical relevance of the overall difference between groups is uncertain. “The absence of a true control group limits the ability to distinguish the effect of either intervention from regular contact with engaged professionals or from practice effects, ie, improvements that result from practice or repetition of task items or activities,” the editorialists cautioned.

Overall, the results suggest 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,” the editorialists concluded.