Middle-aged and older adults with metabolic syndrome had older-appearing brains, a large imaging study from the U.K. Biobank cohort suggested.
Participants with metabolic syndrome had a significantly higher brain age gap than those without metabolic syndrome (β=1.13), reported Abigail Dove, PhD, of the Karolinska Institute in Stockholm, at the Alzheimer’s Association International Conference.
Brain age gap is the difference between a person’s estimated brain age based on MRI and their chronological age. A positive brain age gap can be a predictive biomarker for cognitive decline.
The study findings, published in Alzheimer’s & Dementia, suggest that metabolic syndrome — a cluster of five risk factors for diabetes and cardiovascular disease including hyperglycemia, hypertension, central adiposity, low HDL cholesterol, and high triglycerides — may represent a modifiable target to slow brain aging, Dove suggested.
Each individual component of metabolic syndrome was associated with older brain age. “The relationship between metabolic syndrome and older brain age was dose-dependent,” she observed.
“People with three metabolic syndrome components had brains that appeared about 1 year older than expected based on their chronological age,” Dove told MedPage Today. “This rose to 1.7 years with four components and 2.3 years with all five.”
The risk factors encompassed in metabolic syndrome are highly modifiable through lifestyle changes, she emphasized. “Our findings have an empowering message that the more of these that can be brought under control, the better for brain health,” Dove said.
More than one in three Americans has metabolic syndrome. It is associated with dementia and other neurologic disorders, though how it affects the brain is unclear.
Dove and colleagues studied 27,375 U.K. Biobank participants ages 40 to 70, classifying those with at least three of the five constituent components as having metabolic syndrome. On average, participants were age 54.9 at baseline and had brain MRI 9 years later. About half (46.4%) were college educated and most (93%) were white.
At baseline, 28.5% of participants met criteria for metabolic syndrome. The most prevalent component was hypertension (66.8%), followed by low HDL cholesterol (36.5%), elevated triglycerides (35.9%), central adiposity (24.7%), and hyperglycemia (14.0%).
Brain age was estimated with a machine learning model based on 1,079 phenotypes from MRI data that 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 significantly mediated the association between metabolic syndrome and brain age gap, accounting for between 2.6% and 16.5% of the association.
“This might give us some hints at the pathway linking metabolic syndrome to brain aging,” Dove noted.
The largest proportions of the association were mediated by fatty acids, including omega-6 and other polyunsaturated fats; glycated acetyls that indicated systemic inflammation; and apolipoproteins ApoB and ApoA1, markers of atherosclerosis.
People in the U.K. Biobank were substantially healthier, more socioeconomically advantaged, and less diverse than the general British population, the researchers acknowledged. 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, limiting the ability to characterize longitudinal relationships between metabolic syndrome and brain aging.
