TY - JOUR
T1 - Systemic inflammation during midlife and cognitive change over 20 years
T2 - The ARIC Study
AU - Walker, Keenan A.
AU - Gottesman, Rebecca F.
AU - Wu, Aozhou
AU - Knopman, David S.
AU - Gross, Alden L.
AU - Mosley, Thomas H.
AU - Selvin, Elizabeth
AU - Windham, B. Gwen
N1 - Funding Information:
The Atherosclerosis Risk in Communities Study is conducted as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). Neurocognitive data are collected by U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the NIH (NHLBI, NINDS, NIA, and NIDCD), and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. This study was also supported by contracts T32 AG027668 (Dr. Walker), K24 AG052573 (Dr. Gottesman), and K01 AG050699 (Dr. Gross) from the National Institute on Aging; and K24 DK106414 and R01 DK089174 (Dr. Selvin) from the National Institute of Diabetes and Digestive and Kidney Diseases. The reagents for the C-reactive protein assays were donated by Roche Diagnostics. 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.
Funding Information:
K. Walker reports no disclosures relevant to the manuscript. R.GottesmanisassociateeditorforNeurology® and receives research support from NIH. A. Wu reports no disclosures relevant to the manuscript. D. Knopman serves on a data safety monitoring board for the DIAN Study; is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the Alzheimer’s Disease Cooperative Study; and receives research support from NIH. A. Gross receives research support from NIH. T. Mosley receives research support from NIH. E. Selvin receives research support from NIH. B. Windham is an investigator/dementia expert on a CMS Coverage with Evidence Development (CED) study and has been an investigator in a clinical trial sponsored by ACADIA Pharmaceuticals; receives research support from NIH. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© 2019 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2019/3/12
Y1 - 2019/3/12
N2 - To examine the association between systemic inflammation measured during midlife and 20-year cognitive decline.MethodsWithin 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.ResultsA 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.ConclusionsOur 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.
AB - To examine the association between systemic inflammation measured during midlife and 20-year cognitive decline.MethodsWithin 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.ResultsA 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.ConclusionsOur 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.
UR - http://www.scopus.com/inward/record.url?scp=85062875457&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062875457&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000007094
DO - 10.1212/WNL.0000000000007094
M3 - Article
C2 - 30760633
AN - SCOPUS:85062875457
SN - 0028-3878
VL - 92
SP - E1256-E1267
JO - Neurology
JF - Neurology
IS - 11
ER -