Midlife Systemic Inflammatory Markers Are Associated With Late-Life Brain Volume

Abstract

Background and Objectives To clarify the temporal relationship between systemic inflammation and neurodegeneration, we examined whether a higher level of circulating inflammatory markers during midlife was associated with smaller brain volumes in late-life using a large biracial prospective cohort study. Methods Plasma levels of systemic inflammatory markers (fibrinogen, albumin, white blood cell count, von Willebrand factor, and factor VIII) were assessed at baseline in 1,617 participants (mean age 52 [8] years, 61% female, 26% African American) enrolled in the Atherosclerosis Risk in Communities Study. Using all 5 inflammatory markers, an inflammation composite score was created for each participant. We assessed episodic memory and regional brain volumes, using 3 T MRI, 24 years later. Results Each SD increase in midlife inflammation composite score was associated with 42 mm3 smaller hippocampal (p = 0.08), 204 mm3 smaller occipital (p = 0.07), and 197 mm3 smaller Alzheimer disease (AD) signature region (p = 0.010) volumes 24 years later. Compared with participants with no elevated (fourth quartile) midlife inflammatory markers, participants with elevations in 3 or more markers had significantly smaller AD signature region (−751 mm3; p = 0.038) and hippocampal (−148 mm3; p = 0.038) volumes and reduced episodic memory (p = 0.049). The association between midlife inflammation and late-life brain volume was modified by age, whereby younger participants with higher levels of systemic inflammation during midlife demonstrated significantly reduced late-life brain volumes subsequently. Discussion Our prospective findings provide evidence for what may be an early contributory role of systemic inflammation in neurodegeneration and cognitive aging.