@article{5b344bffe1894808a15201c01b7ea453,
title = "The Association of Mid-and Late-Life Systemic Inflammation with Brain Amyloid Deposition: The ARIC-PET Study",
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, C-reactive protein, amyloid-beta, florbetapir PET, immune system, inflammation",
author = "Walker, {Keenan A.} and Windham, {B. Gwen} and Brown, {Charles H.} and Knopman, {David S.} and Jack, {Clifford R.} and Mosley, {Thomas H.} and Elizabeth Selvin and Wong, {Dean F.} and Hughes, {Timothy M.} and Yun Zhou and Gross, {Alden L.} and Gottesman, {Rebecca F.}",
note = "Funding Information: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, H HSN268201100007C, HHSN268201100008C, HH SN268201100009C, HHSN268201100010C, HHS N268201100011C, and HHSN268201100012C). Neurocognitive data is collected by U01 HL096812, HL096814, HL096899, HL096902, HL096917 from the National Heart, Lung, and Blood Institute and the National Institute of Neurological Disorders and Stroke, with previous brain MRI examinations funded by R01-HL70825 from the National Heart, Lung, and Blood Institute. This study was also supported by contracts T32 AG027668 (Dr. Walker) and K24 AG052573 (Dr. Gottesman) from the National Institute on Aging. The ARIC-PET study is funded by the National Institute on Aging (R01AG040282). Dr. Selvin was supported by NIH/NIDDK grants K24DK106414 and R01DK089174. Dr. Gross was supported by K01-AG050699 from the National Institute on Aging. Avid Radiopharmaceuticals provided the florbetapir isotope for the study, but had no role in the study design or interpretation of results. Reagents for the C-reactive protein assays were donated by Roche Diagnostics Corp. The sponsors had no role in the design and conduct of the study; collection management, analysis and interpretation of the data; or preparation review, or approval of the manuscript. The authors thank the staff and participants of the ARIC study for their important contributions. Publisher Copyright: {\textcopyright} 2018-IOS Press and the authors. All rights reserved.",
year = "2018",
doi = "10.3233/JAD-180469",
language = "English",
volume = "66",
pages = "1041--1052",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
number = "3",
}