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

TitleMidlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease: The Atherosclerosis Risk in Communities Study.
Publication TypeJournal Article
Year of Publication2017
AuthorsWalker KA, Power MC, Hoogeveen RC, Folsom AR, Ballantyne CM, Knopman DS, B Windham G, Selvin E, Jack CR
Secondary AuthorsGottesman RF
JournalStroke
Volume48
Issue12
Pagination3196-3202
Date Published2017 12
ISSN1524-4628
KeywordsAfrican Continental Ancestry Group, Aged, Aged, 80 and over, Apolipoproteins E, Atherosclerosis, Biomarkers, Brain, C-Reactive Protein, Cerebral Infarction, Cerebral Small Vessel Diseases, Diffusion Tensor Imaging, European Continental Ancestry Group, Female, Humans, Male, Prospective Studies, Risk Factors, Socioeconomic Factors, Systemic Inflammatory Response Syndrome, United States, White Matter
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 ( interaction=0.011). Although an association between higher CRP levels and greater WM hyperintensity volume was found only among Īµ4-positive participants in our primary analysis (0.14 SD; 95% confidence interval, 0.01-0.26; 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.

DOI10.1161/STROKEAHA.117.018675
Alternate JournalStroke
PubMed ID29101255
PubMed Central IDPMC5705320
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
T32 AG027668 / AG / NIA NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
K24 DK106414 / DK / NIDDK NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
R01 HL070825 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
K24 AG052573 / AG / NIA NIH HHS / United States