Epigenetic biomarker may reliably measure impact of chronic inflammation on brain

Chronic inflammation appeared linked to neurodegenerative brain changes that affect cognitive ability differences in later life, according to study results published in Neurology.

DNA methylation proxies may help index chronic inflammatory status, researchers noted.

“Low-level, systemic chronic inflammation has emerged as a hallmark and potential driver for individual differences in brain aging,” Eleanor L.S. Conole, BSc, MRes, of the department of psychology at the University of Edinburgh in the U.K., and colleagues wrote. “Yet while chronic inflammation has been consistently linked to dementia, studies investigating peripheral inflammatory markers in nonclinical groups show disparity with respect to cognitive outcomes and have not yet clarified the magnitude and regional extent of brain structural associations.”

The researchers sought to examine the role of chronic inflammation in cognitive aging by comparing epigenetic and serum biomarkers of C-reactive protein (CRP) and their relationships to neuroimaging and cognitive outcomes. They analyzed data of 521 individuals who were cognitively normal at baseline, had a median age of 72.4 years and who had inflammation, vascular risk and neuroimaging data available.

They quantified baseline inflammatory status via CRP, a traditional measure of peripheral inflammation, and DNA methylation signature of CRP (DNAm CRP), an epigenetic measure. Further, the researchers used linear models to assess the inflammation-brain health associations and performed mediation analyses to examine the link between chronic inflammation, brain structure and cognitive functioning.

Results showed associations were an average of 6.4-fold stronger between DNAm CRP vs. serum CRP and brain health outcomes. The researchers reported an association between DNAm CRP and total brain volume (beta = –0.197; 95% CI, –0.28 to –0.12), gray matter volume (beta = –0.2; 95% CI, –0.28 to –0.12) and white matter volume (beta = -0.15; 95% CI –0.23 to –0.07) and regional brain atrophy. Further, they observed an inverse association between DNAm CRP and global and domain-specific cognitive functioning, with brain structure partially mediating the CRP-cognitive association according to lifestyle and health factors.

“By utilizing an epigenetic inflammation measure, which integrates information from multiple immune-related CpG sites, we may provide a more reliable measure of chronic inflammation and thus a more comprehensive overview of the consequences of chronic inflammation on brain structure and function,” Conole and colleagues wrote. “Reliable monitoring of inflammatory exposure could enable clinicians to review the efficacy of drug and lifestyle interventions to attenuate inflammation levels with a view to improving cognitive outcomes.”