Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Mar 27;68(13):1032-8.
doi: 10.1212/01.wnl.0000257815.20548.df.

Inflammatory biomarkers are associated with total brain volume: the Framingham Heart Study

A L Jefferson  1 , J M Massaro, P A Wolf, S Seshadri, R Au, R S Vasan, M G Larson, J B Meigs, J F Keaney Jr, I Lipinska, S Kathiresan, E J Benjamin, C DeCarli
Affiliations

Inflammatory biomarkers are associated with total brain volume: the Framingham Heart Study

A L Jefferson et al. Neurology. .

Abstract

Background: Systemic inflammation is associated with ischemia and Alzheimer disease (AD). We hypothesized that inflammatory biomarkers would be associated with neuroimaging markers of ischemia (i.e., white matter hyperintensities [WMH]) and AD (i.e., total brain volume [TCB]).

Methods: MRI WMH and TCB were quantified on 1,926 Framingham Offspring participants free from clinical stroke, TIA, or dementia (mean age 60 +/- 9 years; range 35 to 85 years; 54% women) who underwent measurement of a circulating inflammatory marker panel, including CD40 ligand, C-reactive protein, interleukin-6 (IL-6), soluble intracellular adhesion molecule-1, monocyte chemoattractant protein-1, myeloperoxidase, osteoprotegerin (OPG), P-selectin, tumor necrosis factor-alpha (TNFalpha), and tumor necrosis factor receptor II. To account for head size, both TCB (TCBV) and WMH (WMH/TCV) were divided by total cranial volume. We used multivariable linear regression to relate 10 log-transformed inflammatory biomarkers to brain MRI measures.

Results: In multivariable models, inflammatory markers as a group were associated with TCBV (p < 0.0001) but not WMH/TCV (p = 0.28). In stepwise models adjusted for clinical covariates with backwards elimination of markers, IL-6 and OPG were inversely associated with TCBV; TNFalpha was inversely related to TCBV in a subset of 1,430 participants. Findings were similar in analyses excluding individuals with prevalent cardiovascular disease. The relations between TCBV and inflammatory markers were modified by both sex and age, and generally were more pronounced in men and in older individuals.

Conclusions: Although our observational cross-sectional data cannot establish causality, they are consistent with the hypothesis that higher inflammatory markers are associated with greater atrophy than expected for age.

PubMed Disclaimer

Conflict of interest statement

Disclosure: The authors report no conflicts of interest.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tarkowski E, Rosengren L, Blomstrand C, et al. Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke. 1995;26:1393–1398. - PubMed
    1. Tarkowski E, Rosengren L, Blomstrand C, et al. Intrathecal release of pro- and anti-inflammatory cytokines during stroke. Clin Exp Immunol. 1997;110:492–499. - PMC - PubMed
    1. Tarkowski E, Tullberg M, Fredman P, Wikkelso C. Correlation between intrathecal sulfatide and TNF-alpha levels in patients with vascular dementia. Dementia Geriatr Cogn Disord. 2003;15:207–211. - PubMed
    1. Yasojima K, Schwab C, McGeer EG, McGeer PL. Human neurons generate C-reactive protein and amyloid P: upregulation in Alzheimer’s disease. Brain Res. 2000;887:80–89. - PubMed
    1. Engelhart MJ, Geerlings MI, Meijer J, et al. Inflammatory proteins in plasma and the risk of dementia: The Rotterdam Study. Arch Neurol. 2004;61:668–672. - PubMed

Publication types

MeSH terms

Grants and funding

  NODES
Association 4
COMMUNITY 1
twitter 2