Narrowing the gap between an individual’s biological and chronological age is linked to better biological and chronological age with a positive influence on long-term neurologic outcomes.

Using blood-based biomarkers investigators assessed biological age acceleration (BAA) in nearly 260,000 adult participants, with a subset of the cohort also undergoing MRI brain imaging.

Participants who narrowed this gap between their biological and chronological ages had lower white matter hyperintensity volumes on MRI imaging and were 23% less likely to experience stroke during follow-up than those whose gap did not improve.

“Taken together, these findings support targeting biological aging as a modifiable pathway to preserve brain health and motivate trials testing whether lowering BAA reduces later-life brain injury and disease,” the investigators, led by Cyprien Rivier, MD, Yale School of Medicine, New Haven, Connecticut, noted.

The main takeaway for clinicians is that biological age is dynamic and can change over time, Rivier told Medscape Medical News.

“The important point is that we’re not just looking at a snapshot. We’re showing that the trajectory of biological aging is associated with meaningful differences in brain outcomes a decade later,” he added.

The findings will be presented at American Academy of Neurology (AAN) 2026 Annual Meeting in April.

Measuring ‘Wear and Tear’

BAA has previously been linked to adverse neurologic outcomes, but it remains unclear whether improvements in BAA could lead to better outcomes.

To evaluate whether differences between biological and chronological age — a marker of overall physiological aging — are linked to brain health and stroke risk the investigators used a biological age measure known as KdmAge which is derived from 18 common blood biomarkers, including cholesterol and white blood cell count.

The measure was applied to a large UK Biobank cohort at baseline (T0; n = 258,169; mean age, 56 years; mean KdmAge, 54 years; 53% women) and again at a repeat visit approximately 6 years later (T1; n = 6085; mean age, 62 years; mean KdmAge, 58 years; 50% women).

At T2, about 10 years after baseline, a subset of participants underwent brain imaging and cognitive assessments.

Results showed that a higher baseline BAA was associated with a poorer MRI profile and poorer cognitive metrics at T2, as well as a higher risk for incident stroke (hazard ratio [HR], 1.41; 95% CI, 1.38-1.45).

Improved BAA was associated with lower white matter intensity volume (-0.13 for each SD in improvement; P < .001) and lower ventricular volume (-0.08 for each SD in improvement; P = .002), as well as reduced risk for ischemic stroke (HR, 0.73; P ~ .02) and any stroke (HR, 0.77; P ~ .03).

Although there were some associations between BAA improvement and cognitive measures at T2, they were no longer significant after adjusting for cardiovascular risk factors.

Overall, BAA improvement was linked to “lower subsequent risk of stroke and improvements in MRI markers of small vessel disease years later, independent of socioeconomic and vascular risk factors,” the investigators wrote. However, the observational study could not prove causality.

“It’s exciting to think that working to modify our biological age could be a pathway to preserving brain health,” Rivier said in a release.

Several behaviors already recommended for brain health — including healthy eating, adequate sleep, and regular physical activity — could “plausibly influence biological aging, and our findings provide additional motivation to emphasize them,” he noted.

Rivier said the next step is to move from observational evidence toward establishing causal links. Researchers are also working to identify which specific biomarkers in the biological age score may drive the brain-specific associations.

“More broadly, we want to understand whether these findings extend beyond stroke and white matter disease to dementia risk, which is another question that matters as populations age,” he added.

Maintenance Matters

Commenting on the findings, Glen R. Finney, MD, director of the Memory and Cognition Program at Geisinger Health System and professor of neurology at Geisinger College of Health Sciences in Wilkes-Barre, Pennsylvania, called the study “intriguing” and said he is looking forward to seeing more details once the findings are published.

“I thought it was interesting that they looked at a number of age-related biological markers in blood and found correlation with some [components] of structural and vascular brain health,” said Finney, who was not involved with the research.

He noted that there have been a number of different strategies used previously by other researchers to try and qualitatively determine biological age based on various health metrics. “Using blood markers is certainly an interesting approach,” Finney said.

Individuals who take good care of their bodies are more likely to experience healthier aging and maintain function and ability over time than those with poorer health habits or multiple medical conditions, he noted.

“You can keep fairly youthful much longer than the time on the clock would make you believe — but you have to work at it,” he added.

For clinicians, he said the findings offer another reminder of the importance of encouraging patients to practice good brain health to help maintain quality of life and functioning across the lifespan.

This study was funded by an AAN/American Heart Association Ralph L. Sacco Scholars Fellowship awarded to Rivier. The investigators and Finney reported having no relevant financial relationships.