Abstract Details

Title An inflammatory marker panel provides insight into immune pathways involved in cognition: the Northern Manhattan Study

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-025

Objective To determine whether immune protein panels add significant information to correlates of cognition.

Background Risk factors for cognitive decline and dementia include traditional vascular risk factors. Immune mechanisms in vascular cognitive impairment and dementia are less well-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 customized, 60-plex, bead-based immunoassay (Affymetrix, Santa Clara, CA). We used LASSO procedures to select markers and their interactions independently associated with cognitive domain scores. We used linear regression models to assess cross-sectional associations of known correlates of cognition (age, education, socioeconomics, vascular factors) with cognitive scores, and assessed model fit before and after addition of LASSO-selected immune markers and interactions, for each domain.

Results Participants (n=1179) had a mean age of 70+8.9 years, 60% were women, and 68% Hispanic. Inclusion of LASSO-selected immune markers improved model fit above other risk factors for each domain (p for likelihood ratio test<0.0001 for all domains). Specific immune markers contributing to >3 domains were hepatocyte growth factor (HGF, maintains synapses and cerebrovascular integrity), CC chemokine CCL11 (eotaxin-1, implicated in brain aging and Alzheimer disease), and serpin E1 (plasminogen activator inhibitor-1); interactions between chemokine CCL5 and serpin E1 and between CCL5 and CCL11 were found in multiple domains. Immune marker effects were comparable to conventional risk factors: for executive function, each standard deviation (SD) increase in CCL11 (beta=-0.052, p=0.016) was associated with equivalent effect to aging three years (3 year beta -0.048, p<0.0001); for memory, HGF (beta per SD=-0.06, p=0.012) had twice the effect of aging (beta per year -0.03, p<0.0001).

Conclusions Immune markers associate with cognitive function in a multi-ethnic cohort. Further work is needed to determine optimal treatment targets.

Authors/Disclosures
Mitchell S. Elkind, MD, MS, FAAN PRESENTER	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.
Yeseon Moon	No disclosure on file
Janet T. DeRosa	No disclosure on file
	No disclosure on file
Tatjana Rundek, MD, PhD	The institution of Dr. Rundek has received research support from NIH.
Clinton B. Wright, MD, FAAN (NINDS)	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. Dr. Wright has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Abali Milne Kalil. 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.
Ralph L. Sacco, MD, MS, FAHA	Dr. Sacco has received personal compensation in the range of $100,000-$499,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. The institution of Dr. Sacco has received research support from NIH, NINDS, NCATS, NIMHD. The institution of Dr. Sacco has received research support from FL Department of Health. Dr. Sacco has received research support from University of Washington, Seattle. Dr. Sacco has received publishing royalties from a publication relating to health care.
	No disclosure on file
Ken Cheung	Ken Cheung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Tsumura.

��ɫ��

��ɫ��