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Cognitive Scores Improve With Lifestyle Changes, Trial Shows
TORONTO -- Two lifestyle interventions -- one structured, the other self-guided -- improved cognition in older adults at risk of cognitive decline, the 2-year U.S. POINTER trial showed.
Global cognitive scores increased from baseline in both the structured group (mean annual increase rate 0.243 SD, 95% CI 0.227-0.258) and the self-guided group (0.213 SD, 95% CI 0.198-0.229), reported Laura Baker, PhD, of Wake Forest University School of Medicine in Winston-Salem, North Carolina, at the Alzheimer's Association International Conference.
The mean annual increase was greater by 0.029 SD (95% CI 0.008-0.050, P=0.008) in the structured compared with the self-guided group. The findings were published simultaneously in JAMA.
Both interventions encouraged physical activity, cognitive activity, healthy diet, social engagement, and cardiovascular health monitoring. They differed in structure, intensity, and accountability.
The study is the first large-scale, randomized clinical trial to show that healthy lifestyle interventions may protect cognitive function in diverse U.S. populations.
"What we have learned -- what we know from this trial -- is that healthy behaviors matter," Baker said in a press briefing.
Compared with the self-guided group, the structured group performed at a level comparable to adults 1 to 2 years younger in age -- an effect that likely increases brain resilience, Baker pointed out.
Research suggests that worldwide dementia risk could fall by 45% if 14 risk factors were modified at various stages of life. Some public health measures -- like improved education and cardiovascular risk management -- may have already had an effect as dementia incidence has declined in the U.S. and other countries, noted Jonathan Schott, MD, of the University College London.
"In addition to general population-level preventive strategies, a complementary approach to dementia prevention is to target individuals at increased risk either via personalized prevention strategies or through structured programs incorporating multiple behavioral modifications such as diet, physical activity, cognitive training, and vascular risk management," Schott wrote in a JAMA editorial
Early evidence for this approach came from the FINGER trial, which demonstrated that a 2-year intervention improved or maintained cognitive performance in at-risk older adults in Finland. The U.S. POINTER findings are broadly in line with FINGER, but its interpretation requires nuance, Schott observed.
"While U.S. POINTER was designed and powered as a head-to-head comparison of the two interventions, and a statistically significant advantage was seen in the group receiving the structured intervention, the clinical relevance of this difference -- roughly a 14% relative benefit -- is uncertain," he wrote.
"Rather than the difference, the more striking finding is perhaps the similarity of the cognitive benefits across both groups, despite the self-guided group requiring only a fraction of the engagement and interventions," Schott pointed out.
U.S. POINTER was a single-blind randomized trial that followed 2,111 participants at five U.S. sites starting in 2019. Participants were ages 60 to 79, had a sedentary lifestyle, a suboptimal diet, and at least two additional risk factors for cognitive decline: a family history of memory impairment, cardiometabolic risk, race and ethnicity, older age, or sex.
Participants were randomly assigned to structured (1,056 people) or self-guided (1,055 people) interventions. The structured group attended 38 team meetings over 2 years and followed a plan of regular moderate- to high-intensity physical exercise, adherence to the MIND diet, cognitive training, social engagement, and cardiovascular health monitoring.
The second group attended six team meetings to encourage self-selected lifestyle changes that best fit their needs and schedules. Study staff provided general encouragement without goal-directed coaching.
The primary comparison was assessed by a composite measure of executive function, episodic memory, and processing speed over 2 years.
Mean age was 68 years and 68.9% were women. More than 30% of participants were from populations typically underrepresented in clinical trials, the researchers said.
In total, 89% of participants completed the year 2 assessment. Based on prespecified subgroup comparisons, the structured intervention benefit was consistent for APOE4 carriers and noncarriers (P=0.95 for interaction), and appeared to be greater for adults with lower versus higher baseline cognition (P=0.02 for interaction). Cognitive benefits were consistent across age, sex, ethnicity, and heart health status.
Fewer adverse events emerged in the structured group (151 serious and 1,091 non-serious events) versus the self-guided group (190 serious and 1,225 non-serious events). A positive COVID-19 test result was the most common adverse event overall and was more frequent in the structured group.
Complex diseases like heart disease and cancer use combination treatment strategies tailored to individual needs, noted co-author Heather Snyder, PhD, of the Alzheimer's Association, which sponsored the trial. "The next generation of treatments for diseases like Alzheimer's will likely integrate drug and non-drug strategies," Snyder said.
"While these results are fascinating and extremely hopeful, how they are rolled out to the public -- especially those at risk for Alzheimer's and other diseases that cause dementia -- needs to be handled with care and individual attention to tailor to the local environment," she added.
The study had several limitations. All participants were at risk of cognitive impairment and findings might not apply to other groups. The trial was not powered to assess dementia outcomes, the researchers acknowledged. The self-guided group did not serve as true controls and the long-terms effects of the interventions are unknown.
The Alzheimer's Association said it will follow participants for 4 more years to assess future cognitive trajectories. The organization also plans to bring U.S. POINTER interventions to other communities.
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