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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.
Glossary
- AD=
- Alzheimer disease;
- ARIC=
- Atherosclerosis Risk in Communities;
- DWR=
- delayed word recall;
- FVIII=
- factor VIII;
- MP-RAGE=
- magnetization-prepared rapid gradient-echo;
- ROI=
- region of interest;
- VWF=
- von Willebrand factor;
- WBC=
- white blood cell
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
This article is republished with corrections from the original version in Neurology, 2017;89(22):2262-2270.
See the Highlighted Changes supplement, showing the changes made in this updated version: links.lww.com/WNL/C930.
See page 375
- Received May 2, 2017.
- Accepted in final form September 8, 2017.
- © 2023 American Academy of Neurology
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