Association of a Multiplex Immune Marker Panel with Incident Cognitive Impairment and Dementia: The Northern Manhattan Study
Mohammad Sheikh1, Yeseon Moon2, Clinton Wright3, Jose Gutierrez2, Tatjana Rundek4, Ken Cheung2, Mady Hornig2, Mitchell Elkind2
1LSU Health Shreveport, 2Columbia University, 3NINDS, 4University of Miami Miller School of Medicine
Objective:
To determine whether a panel of immune markers adds significant information to known correlates of risk of dementia and cognitive impairment.
Background:
The impact of immune mechanisms on dementia risk is incompletely characterized.
Design/Methods:
A subsample of the Northern Manhattan Study, a prospective cohort study in the racially/ethnically diverse population of New York City, underwent comprehensive neuropsychological testing up to three times, at approximately 5-year intervals. Cognitive outcomes were adjudicated as no cognitive impairment, mild cognitive impairment (MCI), or dementia. Immune markers were assessed using a multiplex immunoassay on plasma samples collected at the time of the first neuropsychological test. Least absolute shrinkage and selection operator (LASSO) techniques were employed to yield a panel of immune markers linearly related to the outcome of dementia/MCI vs. no cognitive impairment. Nested logistic regression models were run to determine the independent association of the immune marker panel with dementia/MCI after adjusting for other predictors of risk.
Results:
Among 1179 participants (mean age 70 + 8.9 years, 60% women, 68% Hispanic), immune markers improved model fit above demographic and vascular risk factors (p-value for likelihood ratio test < 0.0001) as correlates of MCI/dementia. Individual immune markers found to be associated with dementia/MCI were C-X-C Motif Chemokine Ligand 9 (CXCL9) and C-C Motif Chemokine Ligand 2 (CCL2). The effect of the immune markers was comparable to traditional risk factors, with CCL2 (per SD) having almost the same effect as 1 year of aging and CXCL9 (per SD) showing approximately twice this magnitude.
Conclusions:
Immune markers are associated with cognitive decline and dementia outcomes in a multi-ethnic cohort. More work is needed to further characterize these associations and determine therapeutic strategies.