Abstract
ObjectiveTo examine the prospective association between blood biomarkers of immune functioning (i.e., innate immune activation, adaptive immunity, and inflammation) and subsequent cognitive decline and clinical progression to mild cognitive impairment (MCI) in cognitively normal individuals.MethodsThe BIOCARD study is an observational cohort study of N = 191 initially cognitively healthy participants (mean age 65.2 years). Blood plasma samples were assayed for markers of chronic inflammation (TNFR1, IL-6), adaptive immunity (CD25), and innate immune activation (CD14 and CD163). Participants were followed annually for ongoing clinical assessment and cognitive testing for up to 7.3 years. Primary study outcomes were progression to MCI and cognitive change over time, as measured by a global factor score encompassing multiple cognitive domains.ResultsHigher levels of plasma TNFR1 were associated with greater risk of progression from normal cognition to MCI (HR: 3.27; 95% confidence interval, CI: 1.27, 8.40). Elevated levels of TNFR1 were also associated with steeper rate of cognitive decline on follow-up but not with baseline cognitive performance. Baseline IL-6 levels and markers of innate and adaptive immune activation showed no relationship with MCI risk or cognitive decline.ConclusionInflammation, mediated by TNF signaling, may play a selective role in the early phase of AD. Accordingly, plasma TNFR1 may facilitate improved prediction of disease progression for individuals in the preclinical stage of AD.
Highlights
Complex and chronic inflammatory responses are evident in the brains of patients with Alzheimer’s disease (AD) dementia
Few studies have evaluated the relationship between cognition and a range of markers of immune functioning in addition to chronic inflammation, including innate immune activation and adaptive immunity
To develop a more complete understanding of how distinct aspects of immune function relate to cognitive decline, and to gain insight into how discrete immune pathways may play a role in the pathophysiology of AD, it is important to consider a range of inflammatory markers
Summary
Complex and chronic inflammatory responses are evident in the brains of patients with Alzheimer’s disease (AD) dementia. In this study, we measured circulating markers of chronic inflammation (TNFR1, IL-6), markers of innate immune activation (CD14 and CD163), and an adaptive immunity marker (CD25, a marker of T-cell activity) to determine whether these measures are associated with cognitive decline and incidence of MCI. These immune system measures were chosen in part because they have not been extensively studied in populations of older adults with respect to cognitive decline, and because their domain specificity may provide unique insights into potential biological connections underlying specific immune pathways and cognitive decline
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