Immune markers are associated with cognitive performance in a multiethnic cohort: The Northern Manhattan Study

Mitchell S.V. Elkind, Michelle Moon, Tatjana Rundek, Clinton B Wright, Ken Cheung, Ralph L. Sacco, Mady Hornig

Research output: Contribution to journalArticlepeer-review


Objective: To determine whether immune protein panels add significant information to correlates of cognition. Background: Immune mechanisms in vascular cognitive aging are incompletely characterized. Design/methods: A subsample of the prospective Northern Manhattan Study underwent detailed neuropsychological testing. Cognitive scores were converted into Z-scores and categorized into four domains (memory, language, processing speed, and executive function) based on factor analysis. Blood samples were analyzed using a 60-plex immunoassay. We used least absolute shrinkage and selection operator (LASSO) procedures to select markers and their interactions independently associated with cognitive scores. Linear regression models assessed cross-sectional associations of known correlates of cognition with cognitive scores, and assessed model fit before and after addition of LASSO-selected immune markers. Results: Among 1179 participants (mean age 70 ± 8.9 years, 60% women, 68% Hispanic), inclusion of LASSO-selected immune markers improved model fit above age, education, and other risk factors (p for likelihood ratio test < 0.005 for all domains). C–C Motif Chemokine Ligand 11 (CCL 11, eotaxin), C-X-C Motif Chemokine Ligand 9 (CXCL9), hepatocyte growth factor (HGF), and serpin E1 (plasminogen activator inhibitor-1) were associated with each of the domains and with overall cognitive function. Immune marker effects were comparable to conventional risk factors: for executive function, each standard deviation (SD) increase in CCL11 was associated with an effect equivalent to aging three years; for memory, HGF had twice the effect of aging. Conclusions: Immune markers associate with cognitive function in a multi-ethnic cohort. Further work is needed to validate these findings and determine optimal treatment targets.

Original languageEnglish (US)
Pages (from-to)186-192
Number of pages7
JournalBrain, Behavior, and Immunity
StatePublished - Oct 2021


  • Cognition
  • Cohort studies
  • Epidemiology
  • Immune function
  • Innate immunity
  • Vascular dementia

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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