Inflammatory biomarkers are associated with changes in cerebral large artery thickness and lumen diameter in older adults

Abstract

AbstractBackgroundAge‐associated remodeling of cerebral large arteries contributes to worse systemic and brain health in older adults. Vessel wall imaging (VWI) is a neuroimaging technique that offers the critical ability to quantify thickness and lumen diameter across arterial segments of the circle of Willis (CoW). 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 over time.MethodsVanderbilt Memory and Aging Project participants were studied (n=96, 73±7 years, 80% male, mean follow‐up=3.0 years). Baseline systemic inflammatory biomarkers (TNF‐α, IL‐6) were quantified from blood plasma samples. Baseline neuroinflammatory biomarkers (sTREM2, YKL‐40, MMP‐2, MMP‐3, MMP‐9) 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 serial VWI MRI. Linear mixed effects regressions related time x inflammatory biomarker (one predictor per model) to longitudinal VWI lumen diameter and thickness outcomes, adjusting for baseline age, sex, race/ethnicity, education, Framingham Stroke Risk Profile, cognitive status, apolipoprotein ε4 status, T1‐weighted intracranial volume, and time.ResultsHigher CSF sTREM2 levels related to faster luminal narrowing (right ACA, p‐value=0.001). Higher CSF YKL‐40 levels related to faster luminal narrowing (right ACA, p‐value=0.07). Lower CSF MMP‐2 levels related to faster wall thickening (left MCA, p‐value<0.05). Lower CSF MMP‐3 levels related to luminal narrowing, while higher CSF MMP‐3 levels related to luminal widening (left ICA, p‐value=0.05). TNF‐α, IL‐6, and MMP‐9 were unrelated to any VWI changes (p‐values>0.14).ConclusionResults suggest neuroinflammatory biomarkers are largely related to longitudinal intracranial artery narrowing and thickening. However, additional associations between MMPs and luminal widening may reflect the mixed nature of MMP activity on cerebrovascular remodeling. Immune responses mediated by astroglial and microglial activity as well as MMPs may be key pathophysiological mechanisms underlying age‐related cerebral arterial remodeling.