Mitchell S V Elkind1, Michelle Moon2, Tatjana Rundek3, Clinton B Wright4, Ken Cheung5, Ralph L Sacco6, Mady Hornig7. 1. Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. Electronic address: mse13@columbia.edu. 2. Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. 3. Department of Neurology, University of Miami, Miami, FL, USA. 4. National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. 5. Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA. 6. Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. 7. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Abstract
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.
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.
Authors: Marlies P Noz; Annemieke Ter Telgte; Kim Wiegertjes; Leo A B Joosten; Mihai G Netea; Frank-Erik de Leeuw; Niels P Riksen Journal: Stroke Date: 2018-12 Impact factor: 7.914
Authors: Paul M Ridker; Brendan M Everett; Tom Thuren; Jean G MacFadyen; William H Chang; Christie Ballantyne; Francisco Fonseca; Jose Nicolau; Wolfgang Koenig; Stefan D Anker; John J P Kastelein; Jan H Cornel; Prem Pais; Daniel Pella; Jacques Genest; Renata Cifkova; Alberto Lorenzatti; Tamas Forster; Zhanna Kobalava; Luminita Vida-Simiti; Marcus Flather; Hiroaki Shimokawa; Hisao Ogawa; Mikael Dellborg; Paulo R F Rossi; Roland P T Troquay; Peter Libby; Robert J Glynn Journal: N Engl J Med Date: 2017-08-27 Impact factor: 91.245
Authors: Karen L Siedlecki; Tatjana Rundek; Mitchell S V Elkind; Ralph L Sacco; Yaakov Stern; Clinton B Wright Journal: J Int Neuropsychol Soc Date: 2011-12-19 Impact factor: 2.892
Authors: Clinton B Wright; Yeseon Moon; Myunghee C Paik; Truman R Brown; LeRoy Rabbani; Mitsuhiro Yoshita; Charles DeCarli; Ralph Sacco; Mitchell S V Elkind Journal: Stroke Date: 2009-08-20 Impact factor: 7.914