Abstract Details

Title Improvements in Biological Age Acceleration Lead to Better Neuroimaging, Clinical, and Cognitive Markers of Brain Health

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) S10 - Advances in Stroke Imaging and Biomarkers (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Objective

We tested whether biological age acceleration (BAA) and improvements in BAA were associated with subsequent MRI markers of small vessel disease, cognition, and stroke.

Background

BAA, the discrepancy between chronological and biological age, captures multisystem aging and is associated with adverse neurological outcomes. Whether improving BAA leads to future brain health benefits remains unknown.

Design/Methods

KDmAge, a biological age measure built from 18 routine blood biomarkers, was derived at baseline (T0) for 258,169 UK Biobank participants (mean age: 56, mean KDmAge: 54, 53% female) and at the repeat visit (T1) (n=6,085, age: 62, KDmAge: 58, 50% female). BAA was obtained by residualizing KDmAge on chronological age. Exposures were baseline BAA and annualized change (ΔBAA/yr, T0->T1). Outcomes were: MRI markers at T2; cognitive performance at T2; and incident stroke (all-type, ischemic) over a median 10-year follow-up. Multivariable linear models were used for MRI and cognition, and Cox for clinical events.

Results

Higher BAA at T0 was associated with poorer MRI profiles at T2, worse cognitive metrics, and higher risk of incident stroke (HR/SD: 1.41, 95%CI: [1.38-1.45]). Improving BAA was associated with more favorable MRI profiles at T2: lower white matter hyperintensity volume (Beta/SD: -0.13 (SE:0.03), p<0.001), better white-matter diffusion metrics, and smaller ventricular volume (Beta/SD: -0.08 (SE:0.02), p=0.002); reduced risk of any stroke (HR/SD: 0.77 [0.61-0.97]), and ischemic stroke (HR/SD: 0.73 [0.56-0.96]). Associations with cognitive metrics at T2 were observed but not significant after adjustment for cardiovascular risk factors, likely reflecting limited power.

Conclusions

BAA and improvement in BAA are associated with lower subsequent risk of stroke and improvements in MRI markers of small vessel disease years later, independent of socioeconomic and vascular risk factors. 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.

Authors/Disclosures
Cyprien Rivier, MD (Yale University) PRESENTER	Dr. Rivier has nothing to disclose.
Shufan Huo, MD, PhD (Yale University)	Dr. Huo has nothing to disclose.
Santiago Clocchiatti-Tuozzo (Yale University, Department of Neurology)	Mr. Clocchiatti-Tuozzo has nothing to disclose.
Daniela B. Renedo, MD (Yale University)	Dr. Renedo has nothing to disclose.
Kevin N. Sheth, MD, FAAN (Yale UniversityDivision of Neuro and Critical Care)	Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell. Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zoll. Dr. Sheth has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NControl. Dr. Sheth has received stock or an ownership interest from Astrocyte. Dr. Sheth has received stock or an ownership interest from Alva. The institution of Dr. Sheth has received research support from Biogen. The institution of Dr. Sheth has received research support from Novartis. The institution of Dr. Sheth has received research support from Bard. The institution of Dr. Sheth has received research support from Hyperfine. Dr. Sheth has received intellectual property interests from a discovery or technology relating to health care.
Guido J. Falcone, MD (Yale School of Medicine)	The institution of Dr. Falcone has received research support from NIH. The institution of Dr. Falcone has received research support from AHA.

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