Interleukin-6 and risk of cognitive decline: MacArthur Studies of Successful Aging
Abstract
OBJECTIVE: To investigate whether plasma interleukin-6 (IL-6) is cross-sectionally related to poorer cognitive function and whether a baseline plasma IL-6 measurement can predict risk for decline in cognitive function in longitudinal follow-up of a population-based sample of nondisabled elderly people. METHODS: A prospective cohort study of 779 high-functioning men and women aged 70 to 79 from the MacArthur Study of Successful Aging was conducted. Regression modeling was used to investigate whether baseline IL-6 levels (classified by tertiles) were associated with initial cognitive function and whether IL-6 levels predicted subsequent declines in cognitive function from 1988 to 1991 (2.5-year follow-up) and from 1988 to 1995 (7-year follow-up). RESULTS: Subjects in the highest tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline cognitive function (i.e., scores below the median), independent of demographic status, social status, health and health behaviors, and other physiologic variables (odds ratio [OR] = 1.46; 95% CI: 0.97, 2.20). At 2.5 years, those in both the second tertile of IL-6 (OR = 2.21; 95% CI: 1.44, 3.42) and the third tertile (OR = 2.03; 95% CI: 1.30, 3.19) were at increased risk of cognitive decline even after adjusting for all confounders. At 7 years of follow-up, only those in the highest IL-6 tertile were significantly more likely to exhibit declines in cognition (OR = 1.90; 95% CI: 1.14, 3.18) after adjustment for all confounders. CONCLUSIONS: The results suggest a relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function. These findings are consistent with the hypothesized relationship between brain inflammation, as measured here by elevated plasma IL-6, and neuropathologic disorders.
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Increased IL-6 levels correlate more closely with NFT burden in AD patients rather than neuritic plaques, as well as with age-related cognitive decline in humans.
“increased IL-6 levels have been shown to correlate more closely with NFT burden in AD patients rather than neuritic plaques [155] as well as age-related cognitive decline in humans [156].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [156]
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- Authors
- Weaver, J. D., Huang, M.-H., Albert, M., Harris, T., Rowe, J. W., & Seeman, T. E.
- Affiliations
- Harvard University (US)
- Venue
- Neurology
- Published
- 2002-08-13
- Volume
- 59
- Issue
- 3
- Pages
- 371-378
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2004349651
- Cited by
- 536
- References
- 24
- Citations by year
- 2026: 7 · 2025: 19 · 2024: 20 · 2023: 23 · 2022: 26 · 2021: 24 · 2020: 21 · 2019: 25 · 2018: 34 · 2017: 25 · 2016: 20 · 2015: 21 · 2014: 33 · 2013: 27 · 2012: 19
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Vermont
- National Institutes of Health (5r01ag017056-03)
- National Institute on Aging (AG17265, P30AG017265, AG 17056)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- interleukin-6, cognitive decline, plasma cytokines, neuroinflammation, cognitive function, older adults, successful aging, neurodegenerative disease risk
- MeSH terms
- Aged, Aging, Analysis of Variance, Cognition Disorders, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Risk Factors, Cohort Studies, Interleukin-6, Multivariate Analysis, Confidence Intervals, Linear Models, Odds Ratio
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