Lifestyle Changes May Slow Brain Aging in Adults Younger Than 70

A structured multidomain lifestyle intervention may help slow changes in brain white matter associated with aging, a secondary analysis of data from the randomized POINTER trial suggested.

Compared with a self-guided intervention, a structured intervention attenuated increases in white matter free water over time (β = -0.031, SE=0.012, P=0.009) in people under age 70, reported Pauline Maillard, PhD, of the University of California Davis, who presented findings from the POINTER Imaging analysis at the Alzheimer’s Association International Conference.

This effect was not seen in participants 70 and older, and no comparable intervention-related interactions were detected for other cerebrovascular MRI markers studied, Maillard and colleagues noted in JAMA Network Open, where the study was published.

“This study provides evidence that a multidomain lifestyle intervention may help slow changes in brain white matter that are associated with aging and cognitive decline,” Maillard said. It suggests earlier intervention, before age 70, may be especially beneficial for preserving brain health, she observed.

“White matter changes are often less emphasized than memory-related brain changes, but they are closely linked to vascular health, brain connectivity, and cognitive function,” Maillard told MedPage Today. “Our findings support the idea that addressing several modifiable risk factors together, including physical activity, diet, cognitive and social engagement, and cardiovascular health, may have measurable effects on the brain.”

“These results should not be interpreted as showing that lifestyle intervention can prevent dementia on its own, but they provide encouraging biological evidence that lifestyle changes may influence brain aging,” she emphasized. “Longer follow-up will be important to determine whether these imaging differences translate into sustained cognitive benefits.”

The POINTER trial tested two lifestyle interventions — one structured, the other self-guided — to see whether they would improve cognitive scores in over 2,000 older adults. Both 2-year interventions encouraged physical activity, cognitive activity, healthy diet, social engagement, and cardiovascular health monitoring, but they differed in structure, intensity, and accountability.

The primary findings, published in 2025, demonstrated greater cognitive benefits in the structured group compared with the self-guided group. The researchers estimated that the structured intervention slowed the cognitive aging clock by about 1 to 2 years.

Data from three of the trial’s ancillary studies — POINTER-NV (neurovascular), POINTER-Neuroimaging, and POINTER-zzz (sleep) — showed that blood pressure regulation, cognitive resilience, and sleep apnea were better with the structured intervention.

In the POINTER Imaging analysis, Maillard and colleagues evaluated 959 participants with a mean age of 68 years; 61.9% were women. Participants underwent MRI at baseline and at up to two follow-up visits at 12 and 24 months.

The primary outcomes were cerebrovascular MRI markers of global white matter free water, fractional anisotropy, peak width of skeletonized mean diffusivity, analysis along the perivascular space index, white matter hyperintensity volume, and incident cerebral microbleeds. Free water was the marker most responsive to lifestyle intervention in adults 60 to 70 years of age, showing attenuated small-vessel disease-related injury, Maillard said.

Baseline free water also identified participants at higher risk for white matter hyperintensity progression and incident cerebral microbleeds, she added.

The imaging cohort was an ancillary subset with a slightly lower proportion of women and a modestly higher prevalence of vascular risk factors than the main study cohort, the researchers acknowledged. The 2-year timeline may be insufficient for tracking certain vascular outcomes.

During the meeting, the Alzheimer’s Association announced a new study based on findings from POINTER and the LatAm-FINGERS study, which showed that a multidomain lifestyle intervention in Latin America led to greater cognitive improvements versus a flexible health-advice intervention.

The global PROTECT-Cog trial will test whether a lifestyle intervention combined with a GLP-1 receptor agonist or similar metabolism-targeting drug can help prevent or delay cognitive decline and dementia, the group said.

“PROTECT-Cog builds directly on what we learned from U.S. POINTER and takes the next critical step in prevention science,” Maria Carrillo, PhD, chief science officer and medical affairs lead at the Alzheimer’s Association, said in a news release. “By testing a combined approach that targets both lifestyle and biology, we have the opportunity to better understand how to meaningfully reduce the risk of cognitive decline before symptoms begin.”