The Association of Mid-and Late-Life Systemic Inflammation with Brain Amyloid Deposition: The ARIC-PET Study

Keenan Walker, B. Gwen Windham, Charles Brown, David S. Knopman, Clifford R. Jack, Thomas H. Mosley, Elizabeth Selvin, Dean Foster Wong, Timothy M. Hughes, Yun Zhou, Alden L Gross, Rebecca F Gottesman

Research output: Contribution to journalArticle

Abstract

Background: Although inflammation has been implicated in the pathogenesis of Alzheimer's disease, the effects of systemic inflammation on brain amyloid deposition remain unclear. Objective: We examined the association of midlife and late-life systemic inflammation with late-life brain amyloid levels in a community sample of non-demented older adults from the Atherosclerosis Risk in Communities (ARIC)-PET Study. Methods: 339 non-demented participants (age: 75 [SD 5]) were recruited from the ARIC Study to undergo florbetapir PET (amyloid) imaging. Blood levels of high sensitivity C-reactive protein (CRP), a marker of systemic inflammation, were measured 22 years (Visit 2), 16 years (Visit 4), and up to 2 years before PET imaging (Visit 5). Elevated brain amyloid deposition (standardized uptake value ratio >1.2) was the primary outcome. Results: Our primary analyses found no association of midlife and late-life CRP with late-life brain amyloid levels. However, in secondary stratified analyses, we found that higher midlife (Visit 2) CRP was associated with elevated amyloid among males (OR 1.65, 95% CI: 1.13-2.42), and among white (OR 1.33, 95% CI: 1.02-1.75), but not African American, participants (p-interactions<0.05). Among male participants, those who maintained high CRP levels (≥3 mg/L) throughout mid-and late-life were most likely to have elevated brain amyloid (OR, 8.81; 95% CI: 1.23, 62.91). Conclusions: Although our primary analysis does not support an association between systemic inflammation and brain amyloid deposition, we found evidence for sex-and race-dependent associations. However, findings from subgroup analyses should be interpreted with caution.

Original languageEnglish (US)
Pages (from-to)1041-1052
Number of pages12
JournalJournal of Alzheimer's Disease
Volume66
Issue number3
DOIs
StatePublished - Jan 1 2018

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Encephalitis
Amyloid
Atherosclerosis
C-Reactive Protein
Brain
Inflammation
African Americans
Alzheimer Disease

Keywords

  • Alzheimer's disease
  • amyloid-beta
  • C-reactive protein
  • florbetapir PET
  • immune system
  • inflammation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

The Association of Mid-and Late-Life Systemic Inflammation with Brain Amyloid Deposition : The ARIC-PET Study. / Walker, Keenan; Windham, B. Gwen; Brown, Charles; Knopman, David S.; Jack, Clifford R.; Mosley, Thomas H.; Selvin, Elizabeth; Wong, Dean Foster; Hughes, Timothy M.; Zhou, Yun; Gross, Alden L; Gottesman, Rebecca F.

In: Journal of Alzheimer's Disease, Vol. 66, No. 3, 01.01.2018, p. 1041-1052.

Research output: Contribution to journalArticle

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AU - Mosley, Thomas H.

AU - Selvin, Elizabeth

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