Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults

Gene Bowman, Loïc Dayon, Richard Kirkland, Jérôme Wojcik, Gwendoline Peyratout, India C. Severin, Hugues Henry, Aikaterini Oikonomidi, Eugenia Migliavacca, Michael Bacher, Julius Popp

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Introduction: Blood-brain barrier (BBB) breakdown is observed in older versus younger adults and in late-onset Alzheimer's disease versus age-matched controls, but its causes and consequences in aging are unclear. We tested the hypothesis that BBB breakdown is associated with cognitive decline and inflammation in nondemented elders. Methods: Cerebrospinal fluid and serum inflammatory markers were measured using sandwich immunoassays in 120 subjects. Least Absolute Shrinkage and Selection Operator-logistic regression selected cerebrospinal fluid and serum signatures that best classified BBB impairment defined by the cerebrospinal fluid albumin index ≥9. Linear regression examined changes in Clinical Dementia Rating sum of boxes as a function of BBB integrity at baseline. Results: Mean age was 70 years, mean Mini–Mental State Examination was 27, and BBB impairment was recorded in 13.5%. BBB breakdown was associated with cognitive decline (P = .015). Cerebrospinal fluid intercellular adhesion molecule-1, vascular endothelial growth factor, interleukin-8, serum amyloid A, macrophage derived chemokine, and gender generated an area under the curve of 0.95 for BBB impairment, and serum IL-16, VEGF-D, IL-15, and other variables generated an AUC of 0.92 for BBB impairment. Serum interleukin-16, vascular endothelial growth factor-D, interleukin-15, and other variables generated an area under the curve of 0.92. Discussion: BBB breakdown is associated with more rapid cognitive decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration, lipid metabolism, and angiogenesis may be implicated. Cell adhesion, neutrophil migration, high-density lipoprotein metabolism, and angiogenesis are implicated.

Original languageEnglish (US)
Pages (from-to)1640-1650
Number of pages11
JournalAlzheimer's and Dementia
Volume14
Issue number12
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

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Keywords

  • Angiogenesis
  • Biomarkers
  • Chemokines
  • CSF
  • Cytokines
  • Elderly
  • HDL metabolism
  • IL-16
  • IL-8
  • MDC
  • Mild cognitive impairment
  • Neurovascular unit
  • Serum
  • Serum amyloid A
  • sICAM-1
  • VEGF

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Bowman, G., Dayon, L., Kirkland, R., Wojcik, J., Peyratout, G., Severin, I. C., Henry, H., Oikonomidi, A., Migliavacca, E., Bacher, M., & Popp, J. (2018). Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults. Alzheimer's and Dementia, 14(12), 1640-1650. https://doi.org/10.1016/j.jalz.2018.06.2857