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

Article type: Research Article

Authors: Walker, Keenan A.^{a; *} | Windham, B. Gwen^b | Brown IV, Charles H.^c | Knopman, David S.^d | Jack Jr, Clifford R.^e | Mosley Jr, Thomas H.^b | Selvin, Elizabeth^f | Wong, Dean F.^g | Hughes, Timothy M.^h | Zhou, Yun^g | Gross, Alden L.^f | Gottesman, Rebecca F.^{a; f}

Affiliations: [a] Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA | [b] Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA | [c] Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA | [d] Department of Neurology, Mayo Clinic, Rochester, MN, USA | [e] Department of Radiology, Mayo Clinic, Rochester, MN, USA | [f] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA | [g] Department of Radiology, Johns Hopkins School of Medicine, Baltimore, MD, USA | [h] Department of Internal Medicine, Section on Gerontology and Geriatrics Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA

Correspondence: [*] Correspondence to: Keenan Walker, PhD, Department of Neurology, Johns Hopkins Hospital, Phipps 446, 600 North Wolfe St., Baltimore, MD 21287, USA. Tel.: +1 626 840 6216; Fax: +1 410 955 0672; E-mail: [email protected].

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.

Keywords: Alzheimer’s disease, amyloid-beta, C-reactive protein, florbetapir PET, immune system, inflammation

DOI: 10.3233/JAD-180469

Journal: Journal of Alzheimer's Disease, vol. 66, no. 3, pp. 1041-1052, 2018