PT  - JOURNAL ARTICLE
AU  - Yian Gu
AU  - Jose Gutierrez
AU  - Irene B. Meier
AU  - Vanessa A. Guzman
AU  - Jennifer J. Manly
AU  - Nicole Schupf
AU  - Adam M. Brickman
AU  - Richard Mayeux
TI  - Circulating inflammatory biomarkers are related to cerebrovascular disease in older adults
AID  - 10.1212/NXI.0000000000000521
DP  - 2019 Jan 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e521
VI  - 6
IP  - 1
4099  - http://nn.neurology.org/content/6/1/e521.short
4100  - http://nn.neurology.org/content/6/1/e521.full
SO  - Neurol Neuroimmunol Neuroinflamm2019 Jan 01; 6
AB  - Objective This investigation aimed at examining whether circulating inflammatory biomarkers C-reactive protein (CRP), interleukin-6 (IL6), and alpha 1-antichymotrypsin (ACT) were related to cerebrovascular disease (CVD) assessed by MRI.Methods The study included nondemented elderly participants of a community-based, multiethnic cohort, who received baseline MRI scans and had CRP (n = 508), ACT (435), and IL6 (N = 357) measured by ELISA. Silent brain infarcts and white matter hyperintensities (WMH) were derived from all available MRI scans at baseline, approximately 4.4 years after blood sample collection for inflammatory biomarkers. Repeated assessments of infarcts and WMH, as well as microbleeds assessment, were performed at follow-up MRI visits around 4.5 years later. Cross-sectional and longitudinal relationship between inflammatory biomarkers and CVD were analyzed using appropriate logistic regression models, generalized linear models, or COX models.Results After adjusting for age, sex, ethnicity, education, APOE genotype, and intracranial volume, 1 SD increase in log10IL6 was associated with infarcts on MRI {odds ratio [OR] (95% confidence interval [CI]) = 1.28 [1.02–1.60], p = 0.033}, and 1 SD increase in log10CRP and log10ACT was associated with microbleeds (OR [95% CI] = 1.46 [1.02–2.09], p = 0.041; and 1.65 [1.11–2.46], p = 0.013; respectively). One SD increase in log10ACT was also associated with larger WMH at the follow-up MRI (b = 0.103, p = 0.012) and increased accumulation of WMH volume (b = 0.062, p = 0.041) during follow-up. The associations remained significant after additional adjustment of vascular risk factors and excluding participants with clinical stroke.Conclusions Among older adults, increased circulating inflammatory biomarkers were associated with the presence of infarcts and microbleeds, WMH burden, and progression of WMH.ACT=alpha 1-antichymotrypsin; APOE=apolipoprotein; BMI=body mass index; CAA=cerebral amyloid angiopathy; CVD=cerebrovascular disease; CRP=C-reactive protein; CV=coefficient of variation; FOV=field of view; GRE=gradient echo; ICV=intracranial volume; IL6=interleukin-6; WHICAP=Washington Heights/Hamilton Heights Inwood Columbia Aging Project; WMH=white matter hyperintensity; sICAM-1=intercellular adhesion molecule-1