MIND Matters: Diet, Exercise, and Engagement in Cognitive Health
September 15, 2025 5 minutes read
By Ellen Feldman, MD
Synopsis: This multicenter, randomized clinical trial showed that a highly structured, multidomain lifestyle intervention modestly but significantly was associated with improved global cognitive function throughout two years in at-risk older adults, compared to a lower-intensity, self-guided program.
Source: Baker LD, Espeland MA, Whitmer RA, et al. Structured vs. self-guided multidomain lifestyle interventions for global cognitive function: The US POINTER randomized clinical trial. JAMA. 2025;334(8):681-691.
The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER trial), a large multicenter, randomized clinical trial, investigated whether structured lifestyle interventions could improve cognitive function in older adults at risk for cognitive decline and dementia.1 Conducted from 2019 to 2025, the trial enrolled 2,111 sedentary adults aged 60-79 years with suboptimal diets and at least two additional risk factors (such as family history, cardiometabolic risks, minority status, older age, or male sex). Participants were randomized to either a high-intensity, structured intervention or a lower-intensity, self-guided program. Both groups received education and encouragement to improve physical activity, cognitive engagement, cardiovascular health, and diet, but the structured group participated in 38 peer group sessions throughout two years, with individualized plans and adherence tracking, while the self-guided group had only six meetings and general guidance.
The MIND (Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurogenerative Delay) diet formed the dietary foundation of both interventions.2 This eating pattern emphasizes daily consumption of leafy greens and other vegetables, regular intake of berries (particularly blueberries and strawberries), whole grains, nuts, olive oil, and moderate consumption of fish and poultry, while limiting butter, cheese, red meats, fried foods, and sweets. Adherence was assessed at baseline and throughout the study with a validated screening tool.
The physical activity component was a key pillar of the structured intervention. Participants received individualized plans to engage in moderate- to high-intensity aerobic activity (four times weekly for 30 minutes), resistance training (twice weekly), and flexibility/balance exercises (twice weekly). While activities often were completed at local community facilities, adherence in the structured group was supported through scheduled group meetings, self-monitoring tools, and coaching. In contrast, the self-guided group received general encouragement without structured exercise prescriptions or monitoring.
The primary outcome was change in global cognitive composite z-score (based on executive function, episodic memory, and processing speed) over two years. Notably, both groups showed cognitive improvement, but the structured group improved more rapidly (+0.243 standard deviations/year vs. +0.213 standard deviations/year) with a statistically significant between-group difference of +0.029 standard deviations/year (95% confidence interval [CI], 0.008-0,050; P = 0.008). The largest domain-specific improvement was seen in executive function — a set of higher-order cognitive processes that enable goal-directed behavior including planning, working memory, problem-solving, and attention control. Interestingly, there were no significant differences observed in episodic memory or processing speed. This domain-specific finding is consistent with prior research.
Notably, adherence was high in both groups. The structured group maintained more than 91% attendance, aided by goal setting, coaching, individualized plans, and dietary monitoring, accompanied with small incentives to encourage healthy food choices. The self-guided group demonstrated strong participation (more than 90% attendance) despite fewer meetings and less support.
Subgroup analysis suggested the structured program had greater benefits for participants with lower baseline cognition, while benefits were consistent across apolipoprotein E ε4 status, age, sex, and cardiovascular risk.
Adverse events were relatively low and similar between groups, although COVID-19 diagnoses were higher in the structured group. There was no increase in musculoskeletal injuries or falls in the structured group.
Commentary
The U.S. POINTER trial provides new, high-quality evidence that a structured, multidomain lifestyle intervention can modestly enhance global cognition over two years in older adults at elevated risk of cognitive decline. Modeled after the well-known Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study, the trial affirms the feasibility and safety of implementing lifestyle-based prevention strategies in diverse U.S. settings.3
The FINGER trial was the first large randomized controlled trial to show that a combination of physical activity, cognitive training, nutritional guidance, and vascular risk factor monitoring could slow cognitive decline in older adults at risk of dementia. The global WW-FINGERS initiative has since aimed to replicate and adapt this multidomain model internationally.3
U.S. POINTER, funded by the Alzheimer’s Association, was designed to test whether a similar intervention could yield cognitive benefits in a more diverse U.S. population. Its use of the MIND diet is a particularly notable component. The MIND diet has been associated with slower cognitive decline and reduced Alzheimer’s disease incidence in observational studies, although randomized trials isolating its effect remain limited.2,4
Both intervention groups in this study (self-guided and structured) showed improvement in cognitive scores over two years, likely reflecting a combination of intervention effects and practice effects (improved performance because of repeated testing). However, as noted, the structured group showed a slightly greater improvement in global cognition (+0.029 standard deviations/year; 95% CI, 0.008-0.050.) This difference, although modest, was statistically significant, could be clinically significant, and aligns with the effect size observed in FINGER.
Interestingly, the benefit was largely driven by improvement in executive function, with no specific differences observed in episodic memory or processing speed. This domain-specific pattern is consistent with prior research suggesting that executive function may be particularly sensitive to interventions that improve vascular health and neuroplasticity (note that this remains a hypothesis and is not a confirmed mechanism).5
A prespecified subgroup analysis showed a more pronounced benefit in participants with lower baseline cognition, suggesting that those with early signs of decline — but without clinical impairment — may be particularly responsive to structured interventions. While promising, this finding should be interpreted cautiously and requires replication in other cohorts. It is worth noting that even the self-guided intervention, which required less resource intensity and had fewer structured touchpoints, was associated with cognitive improvement. This raises the possibility that motivated individuals may benefit from lower-cost or community-based programs. However, without a no-treatment control group, one cannot rule out nonspecific benefits related to study participation alone.
From a clinical standpoint, U.S. POINTER supports the recommendation of multidomain lifestyle interventions as a proactive measure for patients at risk of cognitive decline. Although no clinical outcomes, such as dementia incidence or daily functioning, were assessed, these results can be used to encourage patients to engage in regular physical activity, adopt a brain-healthy diet (such as the MIND diet), maintain social and cognitive engagement, and regularly monitor cardiovascular risk factors.
Ellen Feldman, MD, works for Altru Health System, Grand Forks, ND.
References
- Alzheimer’s Association. U.S. POINTER. https://www.alz.org/us-pointer/home.asp
- Dai L, Lin X, Wang S, et al. The Mediterranean-Dietary Approaches to Stop Hypertension diet intervention for neurodegenerative delay (MIND) diet: A bibliometric analysis. Front Nutr. 2024;11:1348808.
- FINGERS Brain Health Institute. The FINGER study. https://fbhi.se/the-finger-study/
- Barnes LL, Dhana K, Liu X, et al. Trial of the MIND diet for prevention of cognitive decline in older persons. N Engl J Med. 2023;389(7):602-611.
- Zhang Z, Yu Q, Chen Y, et al. A dual-process framework for understanding how physical activity enhances academic performance through domain-general and domain-specific executive functions. Educ Psychol Rev. 2025;37:68.
This multicenter, randomized clinical trial showed that a highly structured, multidomain lifestyle intervention modestly but significantly was associated with improved global cognitive function throughout two years in at-risk older adults, compared to a lower-intensity, self-guided program.
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