Aging
Systemic Inflammation and Its Interaction with Alzheimer’s Disease Biomarkers in Cognitive Decline Diefei Chen* Diefei Chen Chen Chen Chen Chen Chen Johns Hopkins Bloomberg School of Public Health
Systemic inflammation may accelerate Alzheimer’s disease (AD)–related cognitive decline, yet underlying mechanisms remain unclear. We examined whether markers of systemic inflammation are associated with cognitive change and whether they interact with AD biomarkers to accelerate decline. We analyzed 133 participants from the BIOCARD Study who were cognitively unimpaired at baseline and had their first biofluid collection at a mean age of 59.2 years (range: 50-75 years). Participants contributed 2-5 blood samples (median 3) over an average of 21.7 years of follow-up. Blood-based systemic inflammatory markers included IL-1β, IL-6, IL-8, TNFα, TNFR1, and CRP. Baseline biomarkers (Aβ42/40, p-Tau181, GFAP) were measured in both blood and cerebrospinal fluid (CSF). Linear mixed-effects models related (1) baseline systemic inflammation, (2) within-person change in systemic inflammation, and (3) interactions between baseline or change in systemic inflammation and AD biomarkers with longitudinal change in a general cognitive composite, adjusting for age, sex, education, and vascular risk. Higher baseline IL-8 (β=-0.014; 95% CI: -0.027, -0.001) and faster within-person increases in IL-8 (β=-0.006; 95% CI: -0.012, -0.0002) were associated with faster cognitive decline. Higher IL-1β and CRP were more strongly associated with cognitive decline among individuals with high Aβ42/40 (less cortical amyloid), whereas higher IL-1β was more strongly associated with cognitive decline among participants with higher p-tau181, and TNFα was more strongly associated with cognitive decline among participants with higher GFAP. Lower Aβ42/40 interacted with faster increases in CRP to accelerate cognitive decline. Results using CSF-based AD biomarkers were largely consistent with those from blood-based biomarkers. These findings support a conceptual model in which the relationship between systemic inflammation and cognition is disease-stage- and pathology-dependent.