| Key Takeaways: |
|
Intro:
The scientific world has placed great emphasis in recent years on the prevention of cognitive decline for the elderly. Cognitive decline leads to conditions such as Alzheimer’s disease and other forms of dementia, which place a significant burden on patients and their families. To lose memories of loved ones and lose touch with reality is one of the most feared conditions among most older adults.
Unfortunately, once symptoms of cognitive decline start to become apparent, it is increasingly difficult to treat them effectively. Although we do currently have various medications to help slow down cognitive decline in those with established dementia, these treatments are only mildly effective and can have their own set of side effects¹. Exploring various methods of prevention can more fully address the various causes of cognitive decline before they become irreversible. Additionally, pharmaceutical solutions may lead to side effects and complications, especially given that patients are primarily older adults.
As a result, there is a growing focus on finding effective nonpharmacological interventions to help prevent the onset of cognitive decline by targeting risk factors. These nonpharmacological treatments can be safer and cheaper, and may help improve general health aside from just helping prevent cognitive decline¹. Additionally, it is more efficient to prevent cognitive decline from occurring in the first place, rather than struggling to treat dementia after it occurs.
The Lancet Commission’s most recent report on the prevention of dementia identified 14 risk factors that could contribute to dementia development1. These were: lack of education, head injury, vision loss, high cholesterol, physical inactivity, smoking, excessive alcohol consumption, hypertension, obesity, diabetes, hearing loss, depression, infrequent social contact, and air pollution. All of these risk factors present potential areas to target, which, if targeted successfully, may lower dementia risk by up to 45%.
Numerous studies have aimed to address risk factors via lifestyle intervention, and although some have shown benefits, results have been quite mixed. Many of these studies’ protocols may be lacking structure, differing in sample type and size, intensity of intervention, monitoring of patient health and support provided for patients1 . There is a lack of harmonization and standardization across these studies, which can lead to inconsistent findings.
In 2015, a study known as the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was conducted, showing that a 2-year lifestyle intervention for the elderly with increased dementia risk had benefits1 . Then from 2023-2025, the US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (US POINTER) aimed to see how the results observed in a Finnish population compared to a larger, more diverse sample of elderly Americans participants.
How Participants Were Recruited:
Participants for US POINTER were screened in three stages. Firstly, study staff screened through electronic health records and site registries to find potential participants, and used community partners to connect with these individuals1. Then, these individuals were mailed information about US POINTER and sent either hard-copy or online questionnaires to assess if they were eligible to participate. Thirdly, potential participants were reached out to via telephone to confirm that they lived a sedentary lifestyle, and so they could be screened for cognitive capabilities over the phone.
After the three stages of screening, the study staff also conducted three stages of enrolment1. Firstly, a baseline assessment was conducted to verify that patients were eligible. Then, patients were randomly assigned into the two study groups. Finally, participants were informed of their peer teams (Explained in the Study Structure section).
Eligibility Criteria:
In order to be eligible for US POINTER, participants had to be between 60-79 years of age1. They had to have sedentary lifestyles with less than 1 hour a week of moderate to intense physical activity. Their diet had to be suboptimal, with a MIND diet score of under 9. For reference, a MIND diet score measures how closely a person’s diet adheres to the MIND diet recommendations. The MIND diet is a diet designed to improve brain health, to prevent cognitive decline and the development of Alzheimer’s2. It focuses on dark, leafy greens, berries, nuts, whole grains, fish and olive oils, and advises to reduce consumption of sugar and bad fats1.
Additionally, patients had to have a minimum of two out of the following five criteria2:
- Male sex
- Age 70-79
- History of memory loss in immediate family
- High risk ethnicity (American Indian/Alaska Native/Black/African American/African/Middle Eastern/North African/Hispanic/Latino/Spanish)
- Higher cardiovascular risk based on blood pressure/LDL cholesterol/hemoglobin levels.
All five of these criteria placed participants at a higher risk for cognitive decline1. Currently in the United States, 35% of elderly citizens are not meeting exercise guidelines, 81% have a suboptimal diet, and 55% have metabolic syndrome (have three or more of the following risk factors: high blood pressure, high blood sugar, high triglycerides, low HDL cholesterol, large waistline). This shows that the eligibility criteria of US POINTER represents a significant number of elderly Americans, improving the generalizability of the study’s results.
Study Overview:
US POINTER was a 2-year study conducted in order to investigate the impacts of multiple simultaneous lifestyle interventions targeting risk factors in older adults (60-79) at high risk for cognitive decline3. The goal was to see if these lifestyle interventions could successfully protect and preserve cognitive function, via targeting these risk factors. The study included a variety of lifestyle interventions regarding quality of diet, exercise levels, cardiovascular health, and amount of social interaction and cognitive activities, and challenges1. The reason for targeting exercise levels of participants is because exercise is correlated with improved executive function and increased pre-frontal gray matter volume. In addition, a healthier, Mediterranean-style diet can improve cardiovascular health, also improving executive function.
US POINTER was notable because it was among the first of studies to investigate this issue across such a large number of American participants1. It was conducted on 2111 elderly participants at higher-than-average risk for dementia and cognitive decline, 89% of whom completed both years of the study. Moreover, 30% of all participants were among demographic groups that are underrepresented in most modern dementia research3.
Study Structure:
US POINTER consisted of two distinct groups, each undergoing a separate style of intervention1. Participants were randomly assigned into two groups3. The first group underwent the Self-Guided intervention, and the second underwent the Structured intervention. Both interventions focused on the participants exercise, diet, social interaction & cognitive activity levels, and included regular health monitoring. However, both intervention styles differed in structure, with different levels of support and accountability. In both groups, patients were assigned peer teams, groups of 10-15 participants that would have meetings and support one another throughout the course of the study1.
Each participant’s overall cognitive function levels were measured using cognitive test results1. These tests were conducted at the start of the intervention as a baseline, then at every 6 months throughout the 2 year study. The test results were recorded via a global cognitive composite z score, a standardized number measuring overall cognitive function, taken from cognitive test results. These results were taking executive function, episodic memory, and processing speed into equal account. The global cognitive composite z scores were used to measure the change in cognitive function over the 2-year period.
The Two Study Groups:
Patients were assorted randomly into two groups, the first undergoing the Self-Guided intervention, and the second undergoing the Structured intervention1. In both groups, participants were assigned peer teams.
In the Structured Intervention group, the peer teams met 38 times over the 2 years3. This intervention was very structured, prescribing activity plans for participants with specific, quantifiable goals for exercise, diet, and computer-based cognitive challenges, as well as encouragement to engage in social and intellectual activities1.
Participants in the Structured Intervention group were instructed to engage in 30-35 minutes of moderate-to-intense aerobic exercise 4 times per week, 15-20 minutes of strength training 2 times per week, and 10-15 minutes of flexibility training 2 times per week1. They were also instructed to engage in BrainHQ computer cognitive activities for 15-20 minutes 3 times per week.
Participants were also to adhere to the MIND diet1. Specific details of this diet included 1 serving of berries per day, 5 1-ounce servings of nuts per week, a minimum of 3 servings of whole grains per day, 3 servings of legumes per week, 1 serving of fish per week, 2 servings of white, skinless poultry per week, 2 servings of vegetables per week, and a maximum of 3 servings of red or processed meat per week, 1 teaspoon of butter, cream or margarine per week, 1 fried or fast-food meal per week, 4 servings of sweets, pastries or candy bars per week, and 2 1-ounce servings of whole-fat cheese per week.
During peer team meetings, they also engaged in other intellectually stimulating and social activities1. The health of these participants was also regularly monitored. Every 6 months, participants would have appointments with a medical advisor to measure blood pressure, weight, cholesterol, and hemoglobin A1c levels, as well as conduct blood lab tests. Finally, new, updated personal goals were constantly set and reinforced for participants.
In the Self-Guided Intervention group, the peer teams met only 6 times over the 2 years 3. This intervention was less structured, with participants being encouraged to make lifestyle changes to fit their needs and schedules. They were mostly given general encouragement without any specific or tangible goals. They were provided with publicly available educational resources and $75 gift cards at peer team meetings to encourage behavioral changes1. Their health was also monitored less frequently, on an annual basis instead of twice a year.
Study Results:
At the end of the two-year study period, it was found that both lifestyle intervention programs were successful in improving the cognition of these older adults3. It helped protect their memory and thinking capabilities from cognitive decline1.
In both intervention groups, the global cognitive composite z-scores of participants were shown to increase each year1. However, the mean yearly increase in the Structured intervention group was statistically significantly higher than the increase in the Self-Guided intervention group. In conclusion, while both intervention programs showed to improve cognition of participants over the 2-year period, this improvement was higher in the Structured group3. These cognitive benefits were observed regardless of sex, race, cardiovascular health, or genetic risk levels, such as having the high-risk APOE-ε4 gene1. Both participants with and without the APOE-ε4 gene, a high-risk gene for the development of Alzheimer’s disease, had similar levels of cognitive benefit from the intervention programs4.
The mean global cognitive composite z-scores were measured and mapped every ½ year, and the changes from baseline were recorded 1. These cognitive benefits were compared between the Self-Guided and Structured intervention groups. The Structured group’s improvement in executive function was statistically significantly higher than the improvement in the Self-Guided group. The Structured group’s improvement in processing speed was statistically insignificantly higher than the improvement in the Self-Guided group. The improvements in episodic memory were very similar between both intervention groups. Improvement in executive function seemed to be higher for those with lower baseline (before intervention) cognitive function. Unfortunately, participants in the Self-Guided group experienced more serious and nonserious adverse events.
Three big takeaways from this study were as follows2:
1 – Lifestyle interventions were able to be safely implemented into elderly adult groups with strong adherence.
- The intervention program with more structure, accountability and intensity resulted in a statistically significant greater benefit in cognitive power over the 2 year study, as opposed to an intervention program that was less structured.
- This benefit was observed across various subgroups. The benefits were present regardless of APOE ε4 carrier status, sex, age and cardiometabolic health.
Limitations/Future Study Areas:
One major potential complication of this study may be the practice effect – as participants are repeating cognitive tests over time they might just be improving via practice, and not through a genuine improvement in cognitive function as a result of the study1. This may be skewing the results of the study. Future studies and analyses involving additional ways to measure cognitive function such as real-world outcomes and biomarkers, can help strengthen these findings and rule out the practice effect as being responsible for these results.
Unfortunately, the participants in the Structured group did experience more infections and Gastrointestinal health issues1. The Gastrointestinal health issues could be due to the significant diet change in a short period of time. Other limitations of US POINTER are the absence of a real control group, and the short study period of just 2 years. In addition, participants were aware of which group they were part of, which may have led to possible placebo effects.
As a result, while US POINTER delivered incredible results that may help with the battle of dementia and cognitive decline amongst the elderly, further studies are needed to confirm and strengthen these findings, rule out potential biases, and investigate long-term outcomes1.
Sources For Reference:
- Baker, Laura D., et al. “Structured vs Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function.” JAMA, 28 July 2025, doi:10.1001/jama.2025.12923.
- The President and Fellows of Harvard College. “Diet Review: Mind Diet • the Nutrition Source.” The Nutrition Source – Harvard Chan School, Aug. 2023, nutritionsource.hsph.harvard.edu/healthy-weight/diet-reviews/mind-diet/. Accessed 17 Aug. 2025.
- Alzheimer’s Association. “U.S. Pointer Study: Alzheimer’s Association.” U.S. POINTER, 2025, www.alz.org/us-pointer/home.asp. Accessed 17 Aug. 2025.
- “What Is an APOE Gene Test?” Cleveland Clinic, 21 Aug. 2024, my.clevelandclinic.org/health/diagnostics/apoe-gene-test. Accessed 17 Aug. 2025.
