Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease: The Atherosclerosis Risk in Communities Study

Keenan A Walker; Melinda C Power; Ron C Hoogeveen; Aaron R Folsom; Christie M Ballantyne; David S Knopman; B Gwen Windham; Elizabeth Selvin; Clifford R Jack Jr; Rebecca F Gottesman

doi:10.1161/STROKEAHA.117.018675

Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease: The Atherosclerosis Risk in Communities Study

Stroke. 2017 Dec;48(12):3196-3202. doi: 10.1161/STROKEAHA.117.018675. Epub 2017 Nov 3.

Affiliations

¹ From the Department of Neurology (K.A.W., R.F.G.) and Department of Internal Medicine (E.S.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology and Biostatistics, George Washington University Milken Institute School of Public Health (M.C.P.); Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX (R.C.H., C.M.B.); Center for Cardiovascular Disease Prevention, Houston Methodist DeBakey Heart and Vascular Center, TX (R.C.H., C.M.B.); Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.); Department of Neurology (D.S.K.) and Department of Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Department of Medicine, University of Mississippi Medical Center, Jackson (B.G.W.); and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (R.F.G., E.S.). kwalke26@jhmi.edu.
² From the Department of Neurology (K.A.W., R.F.G.) and Department of Internal Medicine (E.S.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology and Biostatistics, George Washington University Milken Institute School of Public Health (M.C.P.); Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX (R.C.H., C.M.B.); Center for Cardiovascular Disease Prevention, Houston Methodist DeBakey Heart and Vascular Center, TX (R.C.H., C.M.B.); Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.R.F.); Department of Neurology (D.S.K.) and Department of Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Department of Medicine, University of Mississippi Medical Center, Jackson (B.G.W.); and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (R.F.G., E.S.).

Abstract

Background and purpose: It is currently unclear whether midlife systemic inflammation promotes the development of white matter (WM) abnormalities and small vessel disease in the elderly. We examined the association of midlife systemic inflammation with late-life WM hyperintensity volume, deep and periventricular WM microstructural integrity (fractional anisotropy and mean diffusivity [MD]), cerebral infarcts, and microbleeds in a biracial prospective cohort study.

Methods: Linear and logistic regression examined the relation between midlife high-sensitivity C-reactive protein (CRP)-a nonspecific marker of inflammation-and brain magnetic resonance imaging markers assessed 21 years later in the Atherosclerosis Risk in Communities Study.

Results: We included 1485 participants (baseline age, 56[5]; 28% black). After adjusting for demographic factors and cardiovascular disease, each SD increase in midlife CRP was associated with lower fractional anisotropy (-0.09 SD; 95% confidence interval, -0.15 to -0.02) and greater MD (0.08 SD; 95% confidence interval, 0.03-0.15) in deep WM and lower fractional anisotropy (-0.07 SD; 95% confidence interval, -0.13 to 0.00) in periventricular WM. We found stronger associations between CRP and periventricular WM microstructural integrity among black participants (P interaction=0.011). Although an association between higher CRP levels and greater WM hyperintensity volume was found only among APOE ε4-positive participants in our primary analysis (0.14 SD; 95% confidence interval, 0.01-0.26; P interaction=0.028), this relationship extended to the entire sample after accounting for differential attrition. Midlife CRP was not associated with the presence of cerebral infarcts or microbleeds in late life.

Conclusions: Our findings support the hypothesis that midlife systemic inflammation may promote the development of chronic microangiopathic structural WM abnormalities in the elderly.

Keywords: cerebrovascular disorders; diffusion tensor imaging; inflammation; magnetic resonance imaging; risk factors.

MeSH terms

Aged
Aged, 80 and over
Apolipoproteins E / blood
Apolipoproteins E / genetics
Atherosclerosis / epidemiology*
Biomarkers
Black People
Brain / pathology
C-Reactive Protein / analysis
Cerebral Infarction / epidemiology
Cerebral Small Vessel Diseases / epidemiology*
Cerebral Small Vessel Diseases / pathology*
Diffusion Tensor Imaging
Female
Humans
Male
Prospective Studies
Risk Factors
Socioeconomic Factors
Systemic Inflammatory Response Syndrome / epidemiology*
Systemic Inflammatory Response Syndrome / pathology*
United States / epidemiology
White Matter / pathology*
White People

Substances

Apolipoproteins E
Biomarkers
C-Reactive Protein

Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease: The Atherosclerosis Risk in Communities Study

Authors

Affiliations

Abstract

MeSH terms

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