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Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study.

TitleMidlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study.
Publication TypeJournal Article
Year of Publication2017
AuthorsWalker KA, Hoogeveen RC, Folsom AR, Ballantyne CM, Knopman DS, B Windham G, Jack CR
Secondary AuthorsGottesman RF
Date Published2017 Nov 28
KeywordsAfrican Americans, Age Factors, Aged, Atherosclerosis, Brain, European Continental Ancestry Group, Factor VIII, Female, Fibrinogen, Humans, Inflammation, Leukocyte Count, Magnetic Resonance Imaging, Male, Memory, Episodic, Middle Aged, Neurodegenerative Diseases, Prospective Studies, Residence Characteristics, Risk Factors, Sex Factors, von Willebrand Factor

OBJECTIVE: 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 1,633 participants (mean age 53 [5] years, 60% female, 27% 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 3T MRI, 24 years later.

RESULTS: Each SD increase in midlife inflammation composite score was associated with 1,788 mm greater ventricular ( = 0.013), 110 mm smaller hippocampal ( = 0.013), 519 mm smaller occipital ( = 0.009), and 532 mm smaller Alzheimer disease signature region ( = 0.008) volumes, and reduced episodic memory ( = 0.046) 24 years later. Compared to participants with no elevated (4th quartile) midlife inflammatory markers, participants with elevations in 3 or more markers had, on average, 5% smaller hippocampal and Alzheimer disease signature region volumes. The association between midlife inflammation and late-life brain volume was modified by age and race, whereby younger participants and white participants with higher levels of systemic inflammation during midlife were more likely to show reduced brain volumes subsequently.

CONCLUSIONS: Our prospective findings provide evidence for what may be an early contributory role of systemic inflammation in neurodegeneration and cognitive aging.

Alternate JournalNeurology
PubMed ID29093073
PubMed Central IDPMC5705246
Grant ListU01 HL096812 / HL / NHLBI NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
K24 AG052573 / AG / NIA NIH HHS / United States