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Abstract
Objective To test the hypothesis that the inflammatory marker plasma soluble CD14 (sCD14) associates with incident dementia and related endophenotypes in 2 community-based cohorts.
Methods Our samples included the prospective community-based Framingham Heart Study (FHS) and Cardiovascular Health Study (CHS) cohorts. Plasma sCD14 was measured at baseline and related to the incidence of dementia, domains of cognitive function, and MRI-defined brain volumes. Follow-up for dementia occurred over a mean of 10 years (SD 4) in the FHS and a mean of 6 years (SD 3) in the CHS.
Results We studied 1,588 participants from the FHS (mean age 69 ± 6 years, 47% male, 131 incident events) and 3,129 participants from the CHS (mean age 72 ± 5 years, 41% male, 724 incident events) for the risk of incident dementia. Meta-analysis across the 2 cohorts showed that each SD unit increase in sCD14 was associated with a 12% increase in the risk of incident dementia (95% confidence interval 1.03–1.23; p = 0.01) following adjustments for age, sex, APOE ε4 status, and vascular risk factors. Higher levels of sCD14 were associated with various cognitive and MRI markers of accelerated brain aging in both cohorts and with a greater progression of brain atrophy and a decline in executive function in the FHS.
Conclusion sCD14 is an inflammatory marker related to brain atrophy, cognitive decline, and incident dementia.
Glossary
- 3MSE=
- Modified Mini-Mental State Examination;
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- CD14=
- cluster of differentiation 14;
- CHS=
- Cardiovascular Health Study;
- CI=
- confidence interval;
- CRP=
- C-reactive protein;
- CVD=
- cardiovascular disease;
- DSM-IV=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
- DSST=
- Digit Symbol Substitution Test;
- FHS=
- Framingham Heart Study;
- FLAIR=
- fluid-attenuated inversion recovery;
- HR=
- hazard ratio;
- IL-6=
- interleukin 6;
- mCD14=
- membrane-bound cluster of differentiation 14;
- MMSE=
- Mini-Mental State Examination;
- NSAID=
- nonsteroidal anti-inflammatory drug;
- sCD14=
- soluble cluster of differentiation 14;
- SPGR=
- spoiled gradient-recalled echo;
- WMHV=
- white matter hyperintensity volume
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally as co–first authors.
↵† These authors contributed equally as co–senior authors.
- Received January 22, 2019.
- Accepted in final form July 18, 2019.
- © 2019 American Academy of Neurology
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