Systemic inflammation during midlife and cognitive change over 20 years: The ARIC Study

Keenan A. Walker, Rebecca F. Gottesman, Aozhou Wu, David S Knopman, Alden L. Gross, Thomas H. Mosley, Elizabeth Selvin, B. Gwen Windham

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

OBJECTIVE: To examine the association between systemic inflammation measured during midlife and 20-year cognitive decline. METHODS: Within the Atherosclerosis Risk in Communities cohort study, inflammatory biomarkers were measured during middle adulthood. We created an inflammation composite score using 4 blood biomarkers measured at visit 1 (fibrinogen, white blood cell count, von Willebrand factor, and factor VIII); we measured C-reactive protein (CRP) at visit 2. Cognition was assessed over 3 visits spanning 20 years using measures of memory, executive function, and language. RESULTS: A total of 12,336 participants (baseline age 56.8 [5.7], 21% black, 56% women) were included. After adjusting for demographic variables, vascular risk factors, and comorbidities, each standard deviation (SD) increase in midlife inflammation composite score was associated with an additional 20-year decline of -0.035 SD (95% confidence interval: -0.062 to -0.007) on the cognitive composite score. We found a similar association between each SD increase in midlife CRP level and additional 20-year cognitive decline (-0.038 SD, 95% confidence interval: -0.057 to -0.019). Participants with a midlife inflammation composite score in the top quartile had a 7.8% steeper cognitive decline, compared to participants in the lowest quartile; CRP in the top quartile was associated with an 11.6% steeper cognitive decline. In cognitive domain-specific analyses, elevated midlife inflammatory markers were most consistently associated with declines in memory. Results were similar after adjusting for attrition using inverse probability weighting. CONCLUSIONS: Our findings highlight what may be an early pathogenic role for systemic inflammation as a driver of cognitive decline in the decades leading up to older adulthood.

Original languageEnglish (US)
Pages (from-to)e1256-e1267
JournalNeurology
Volume92
Issue number11
DOIs
StatePublished - Mar 12 2019

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Inflammation
C-Reactive Protein
Biomarkers
Confidence Intervals
Executive Function
Leukocyte Count
Fibrinogen
Cognition
Comorbidity
Atherosclerosis
Cohort Studies
Language
Demography
Cognitive Dysfunction

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Walker, K. A., Gottesman, R. F., Wu, A., Knopman, D. S., Gross, A. L., Mosley, T. H., ... Windham, B. G. (2019). Systemic inflammation during midlife and cognitive change over 20 years: The ARIC Study. Neurology, 92(11), e1256-e1267. https://doi.org/10.1212/WNL.0000000000007094

Systemic inflammation during midlife and cognitive change over 20 years : The ARIC Study. / Walker, Keenan A.; Gottesman, Rebecca F.; Wu, Aozhou; Knopman, David S; Gross, Alden L.; Mosley, Thomas H.; Selvin, Elizabeth; Windham, B. Gwen.

In: Neurology, Vol. 92, No. 11, 12.03.2019, p. e1256-e1267.

Research output: Contribution to journalArticle

Walker, KA, Gottesman, RF, Wu, A, Knopman, DS, Gross, AL, Mosley, TH, Selvin, E & Windham, BG 2019, 'Systemic inflammation during midlife and cognitive change over 20 years: The ARIC Study', Neurology, vol. 92, no. 11, pp. e1256-e1267. https://doi.org/10.1212/WNL.0000000000007094
Walker, Keenan A. ; Gottesman, Rebecca F. ; Wu, Aozhou ; Knopman, David S ; Gross, Alden L. ; Mosley, Thomas H. ; Selvin, Elizabeth ; Windham, B. Gwen. / Systemic inflammation during midlife and cognitive change over 20 years : The ARIC Study. In: Neurology. 2019 ; Vol. 92, No. 11. pp. e1256-e1267.
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AU - Gross, Alden L.

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AU - Selvin, Elizabeth

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AB - OBJECTIVE: To examine the association between systemic inflammation measured during midlife and 20-year cognitive decline. METHODS: Within the Atherosclerosis Risk in Communities cohort study, inflammatory biomarkers were measured during middle adulthood. We created an inflammation composite score using 4 blood biomarkers measured at visit 1 (fibrinogen, white blood cell count, von Willebrand factor, and factor VIII); we measured C-reactive protein (CRP) at visit 2. Cognition was assessed over 3 visits spanning 20 years using measures of memory, executive function, and language. RESULTS: A total of 12,336 participants (baseline age 56.8 [5.7], 21% black, 56% women) were included. After adjusting for demographic variables, vascular risk factors, and comorbidities, each standard deviation (SD) increase in midlife inflammation composite score was associated with an additional 20-year decline of -0.035 SD (95% confidence interval: -0.062 to -0.007) on the cognitive composite score. We found a similar association between each SD increase in midlife CRP level and additional 20-year cognitive decline (-0.038 SD, 95% confidence interval: -0.057 to -0.019). Participants with a midlife inflammation composite score in the top quartile had a 7.8% steeper cognitive decline, compared to participants in the lowest quartile; CRP in the top quartile was associated with an 11.6% steeper cognitive decline. In cognitive domain-specific analyses, elevated midlife inflammatory markers were most consistently associated with declines in memory. Results were similar after adjusting for attrition using inverse probability weighting. CONCLUSIONS: Our findings highlight what may be an early pathogenic role for systemic inflammation as a driver of cognitive decline in the decades leading up to older adulthood.

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