Inflammatory markers and imaging patterns of advanced brain aging in the general population

Deborah Janowitz, Mohamad Habes, Jon B. Toledo, Anke Hannemann, Stefan Frenzel, Jan Terock, Christos Davatzikos, Wolfgang Hoffmann, Hans Jörgen Grabe

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Inflammaging describes the complexity between low-grade chronic inflammation with the pathogenesis of brain aging and Alzheimer´s disease (AD). We aimed to find associations of inflammatory markers: i) white blood cell count (WBC), ii) high-sensitivity C-reactive protein (hs-CRP), and iii) fibrinogen with brain structures, sensitive neuroimaging markers of advanced brain aging and AD-like atrophy, and cognitive aging scores. We analyzed magnetic resonance imaging (MRI) scans of 2204 participants from the Study of Health in Pomerania-2 (SHIP-2) and SHIP-Trend (55.6% women, mean age 52.4±13.7 years). Associations of the inflammatory markers with specific brain signatures of brain aging (SPARE-BA), AD-like brain atrophy (SPARE-AD) and white matter disease (white matter hyperintensities volume (WMHV)) were investigated. Furthermore we explored their association with general brain structures including total brain volume (TBV), gray matter volume (GMV), and white matter volume (WMV), as well as cognitive scores (Nurnberger Age Inventory (NAI); Verbal Learning and Memory Test (VLMT). We adjusted for multiple vascular risk factors (VRF; e.g. smoking and blood pressure) and corresponding medication use to take their brain aging effects into account and corrected for false-discovery rate (FDR). Results:WBC was inversely associated with SPARE-BA (FDR-adjusted p=0.003), TBV (FDR-adjusted p=0.019) and GMV (FDR-adjusted p= 0.017). GMV was also inversely associated with hs-CRP (FDR-adjusted p=0.039) and fibrinogen (FDR-adjusted p=0.039). None of the inflammatory markers was associated with WMHV. Regression analysis also revealed a trend-level interaction between intake of antiinflammatory medication and hs-CRP with brain aging (SPARE-BA; FDR-adjusted p=0.062). Inflammatatory markers are associated with neuroimaging markers, with elevated WBC leading to significant acceleration in brain aging patterns but not with AD-like imaging structural changes. Given the overlap between accelerated brain aging and AD-like atrophy, increased WBC might be associated with global dementia symptoms due to this overlap in atrophy patterns. Elevated WBC may be not causal to preclinical AD dementia, but an accessory symptom of inflammaging. At population level, our results support the relevant roles of inflammatory markers on brain aging related atrophy.

Original languageEnglish (US)
Pages (from-to)1108-1117
Number of pages10
JournalBrain Imaging and Behavior
Volume14
Issue number4
DOIs
StatePublished - Aug 1 2020
Externally publishedYes

Keywords

  • Alzheimers
  • Epidemiology
  • Inflammation
  • Neuroimaging
  • hs-C-reactive protein

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Cognitive Neuroscience
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Behavioral Neuroscience

Fingerprint Dive into the research topics of 'Inflammatory markers and imaging patterns of advanced brain aging in the general population'. Together they form a unique fingerprint.

  • Cite this

    Janowitz, D., Habes, M., Toledo, J. B., Hannemann, A., Frenzel, S., Terock, J., Davatzikos, C., Hoffmann, W., & Grabe, H. J. (2020). Inflammatory markers and imaging patterns of advanced brain aging in the general population. Brain Imaging and Behavior, 14(4), 1108-1117. https://doi.org/10.1007/s11682-019-00058-y