Association of a Multiplex Immune Marker Panel with Incident Cognitive Impairment and Dementia: The Northern Manhattan Study (P4-9.013)

To determine whether a panel of immune markers adds significant information to known correlates of risk of dementia and cognitive impairment. The impact of immune mechanisms on dementia risk is incompletely characterized. 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. 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. 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. Disclosure: Dr. Sheikh has nothing to disclose. An immediate family member of Dr. Wright has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. An immediate family member of Dr. Wright has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MARSHALL DENNEHY. The institution of an immediate family member of Dr. Wright has received research support from Oncospace. Dr. Wright has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Wright has received personal compensation in the range of $500-$4,999 for serving as a surveyor with ASTRO. Dr. Gutierrez has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Roetzel & Andress, JOHN ASTUNO, JR. L.L.C.. The institution of Dr. Gutierrez has received research support from NIH. Dr. Gutierrez has received publishing royalties from a publication relating to health care. Dr. Gutierrez has received publishing royalties from a publication relating to health care. The institution of Dr. Rundek has received research support from NIH. Ken Cheung has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Deck Therapeutics. The institution of Mady Hornig has received research support from NIH. The institution of Mady Hornig has received research support from The Korein Family Foundation. Dr. Elkind has received personal compensation for serving as an employee of American Heart Association. Dr. Elkind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Atria Academy. The institution of Dr. Elkind has received research support from BMS-Pfizer Alliance for Eliquis. The institution of Dr. Elkind has received research support from Roche. Dr. Elkind has received publishing royalties from a publication relating to health care. Dr. Elkind has a non-compensated relationship as a Officer with American Heart Association that is relevant to AAN interests or activities.