U.K. — Karolinska Institute researcher Abigail Dove, PhD, presented study findings at the Alzheimer's Association International Conference showing that metabolic syndrome is linked to accelerated brain aging, with the pace of aging increasing alongside the number of components a person carries. The results indicate that each additional component of the syndrome corresponds to a larger gap between a person's estimated brain age and their chronological age.

Participants with metabolic syndrome had a higher brain age gap than those without the condition, with a statistical estimate of β=1.13. Dove said that people with three metabolic syndrome components had brains that appeared about 1 year older than expected based on their chronological age. This increased to 1.7 years with four components and 2.3 years with all five.

Brain age gap is the difference between a person's estimated brain age based on MRI and their chronological age, and a positive brain age gap can be a predictive biomarker for cognitive decline. Metabolic syndrome is a cluster of five risk factors for diabetes and cardiovascular disease including hyperglycemia, hypertension, central adiposity, low HDL cholesterol, and high triglycerides. Participants with at least three of the five constituent components were classified as having metabolic syndrome. Metabolic syndrome is associated with dementia and other neurologic disorders, though how it affects the brain has been unclear.

The study included 27,375 U.K. Biobank participants ages 40 to 70, with an average baseline age of 54.9. At baseline, 28.5% of participants met criteria for metabolic syndrome. Participants had brain MRI 9 years after baseline.

Among the components of metabolic syndrome in the study, the most prevalent was hypertension at 66.8%. Low HDL cholesterol was present in 36.5% of participants, elevated triglycerides were present in 35.9%, central adiposity was present in 24.7%, and hyperglycemia was present in 14.0%.

Brain age was estimated using a machine learning model based on 1,079 phenotypes from MRI data. The MRI data assessed regional brain volumes, white matter hyperintensities, microbleeds, white matter microstructural integrity, and functional connectivity during rest and during active engagement. Baseline blood samples were used to assess levels of 33 plasma metabolites. Eight metabolites mediated the association between metabolic syndrome and brain age gap, accounting for between 2.6% and 16.5% of the association.

The largest proportions of the association between metabolic syndrome and brain age gap were mediated by fatty acids, including omega-6 and other polyunsaturated fats. Glycated acetyls that indicated systemic inflammation mediated portions of the association. Apolipoproteins ApoB and ApoA1, markers of atherosclerosis, mediated portions of the association.

"This might give us some hints at the pathway linking metabolic syndrome to brain aging," she said. "Our findings have an empowering message that the more of these that can be brought under control, the better for brain health." More than one in three Americans has metabolic syndrome.

Certain characteristics of the study sample were noted. In the overall study population, 46.4% of participants were college educated and 93% were white. People in the U.K. Biobank were substantially healthier, more socioeconomically advantaged, and less diverse than the general British population. Participants with neuroimaging and metabolite biomarker data were younger, more highly educated, and metabolically healthier than the overall U.K. Biobank sample.

Brain MRI data were available at one time point, and the single time point for MRI data limits the ability to characterize longitudinal relationships between metabolic syndrome and brain aging. The study findings were published in Alzheimer's & Dementia.

Metabolic syndrome affects more than one in three Americans and is a known risk factor for diabetes, cardiovascular disease, dementia, and other neurologic disorders. The mechanisms by which it influences brain aging have not been established. The identification of specific metabolites, particularly fatty acids and inflammatory markers, that mediate the association between metabolic syndrome and brain age gap opens a potential pathway for understanding how the condition accelerates brain aging and may inform future research into interventions targeting brain health.