AUTHOR=Bettcher Brianne M. , Neuhaus John , Wynn Matthew J. , Elahi Fanny M. , Casaletto Kaitlin B. , Saloner Rowan , Fitch Ryan , Karydas Anna , Kramer Joel H. 

TITLE=Increases in a Pro-inflammatory Chemokine, MCP-1, Are Related to Decreases in Memory Over Time

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=11

YEAR=2019

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2019.00025

DOI=10.3389/fnagi.2019.00025

ISSN=1663-4365

ABSTRACT=<p><bold>Objective</bold>: To determine the longitudinal relationship between monocyte chemotactic protein 1 (MCP-1)/CCL2 and memory function in older adults.</p><p><bold>Methods</bold>: We examined longitudinal plasma MCP-1/CCL2 levels and a longitudinal verbal memory measure (CVLT-II 20’ recall) in a sample of 399 asymptomatic older adults (mean age = 72.1). Total visits ranged from 1 to 8, with an average time of 2.1 years between each visit, yielding 932 total observations. In order to isolate change over time, we decomposed MCP-1/CCL2 into subject-specific means and longitudinal deviations from the mean. The decomposed MCP-1/CCL2 variables were entered as predictors in linear mixed effects models, with age at baseline, sex, and education entered as covariates and recall as the longitudinal outcome. In follow-up analyses, we controlled for global cognition and <italic>APOE</italic> genotype, as well as baseline vascular risk factors. We also examined the specificity of findings by examining the longitudinal association between the MCP-1/CCL2 variables and non-memory cognitive tests.</p><p><bold>Results</bold>: Within-subject increases in MCP-1/CCL2 levels were associated with decreases in delayed recall (<italic>t</italic> = −2.65; <italic>p</italic> = 0.01) over time. Results were independent of global cognitive function and APOE status (<italic>t</italic> = −2.30, <italic>p</italic> = 0.02), and effects remained when controlling for baseline vascular risk factors (<italic>t</italic> = −1.92, <italic>p</italic> = 0.05). No associations were noted between within-subject increases in MCP-1/CCL2 levels and other cognitive domains.</p><p><bold>Conclusions</bold>: In an asymptomatic aging adult cohort, longitudinal increases in MCP-1/CCL2 levels were associated with longitudinal decline in memory. Results suggest that “healthy aging” is typified by early remodeling of the immune system, and that the chemokine, MCP-1/CCL2, may be associated with negative memory outcomes.</p>