Inflammatory biomarkers are associated with cerebral large artery thickening and dilatation in older adults

Abstract

AbstractBackgroundAge‐associated changes in intracranial large arteries, including hypertrophic and dilatative remodeling, contribute to worse systemic and brain health in older adults. Vessel wall imaging (VWI) is a novel neuroimaging technique that offers the critical ability to quantify thickness and lumen diameter across arterial segments of the circle of Willis (CoW). Research suggests inflammation, a well‐known feature of aging, cerebrovascular disease, and Alzheimer’s disease, may be a central driver of age‐related changes in CoW morphology. We investigate if fluid biomarkers of inflammation predict key features of intracranial arterial aging, including CoW thickening and dilatation visible on VWI MRI.MethodsVanderbilt Memory & Aging Project participants free of clinical stroke and dementia were studied (n=117, 74±7 years, 73% male). Systemic inflammatory biomarkers (TNF‐α, IL‐6) were quantified from blood plasma samples and neuroinflammatory biomarkers (sTREM2, YKL‐40) were quantified from cerebrospinal fluid samples. Intracranial artery lumen diameter and thickness were manually measured across the basilar artery (BA) and bilateral segments of the internal carotid artery (ICA), anterior cerebral artery (ACA), and middle cerebral artery (MCA) using VWI MRI. Linear regressions related each inflammatory biomarker to intracranial artery lumen diameter and thickness in separate cross‐sectional models, adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile, diagnosis, apolipoprotein ε4 status, and T1‐weighted intracranial volume.ResultsTNF‐α was related to right ICA thickness (b=0.01, p=0.03), left ICA thickness (b=0.01, p<0.05), and left ACA thickness (b=‐0.01, p=0.04); TNF‐α was unrelated to lumen diameters (p>0.51). IL‐6 was related to right ICA thickness (b=0.01, p=0.003) and was unrelated to lumen diameters (p>0.18). sTREM2 was related to left MCA lumen diameter (b=0.0001, p=0.03), right ACA lumen diameter (b=0.0001; p=0.001), and right ACA thickness (b=0.00003, p=0.03). YKL‐40 was unrelated to intracranial artery thickness (p>0.27) and lumen diameter (p>0.05).ConclusionsResults suggest TNF‐α, IL‐6, and sTREM2 are related to intracranial large artery thickening, and sTREM2 may further relate to large artery dilatation. Given the increased reliability of ICA and BA manual measurements on VWI MRI, these findings may be most robust. Proinflammatory cytokines and microglia‐mediated immune responses may be key pathophysiological mechanisms underlying age‐related arterial remodeling within the brain.