Chronic Systemic Inflammation Is Associated With Symptoms of Late-Life Depression: The ARIC Study

Objective: The current study examined how the pattern of systemic inflammation in the decades leading up to late-life relates to depression symptoms in older adults.

Methods: Within the Atherosclerosis Risk in Communities Study, we measured high-sensitivity C-reactive protein (CRP), a nonspecific marker of systemic inflammation, at three visits: 21 years and 14 years before, and concurrent with the assessment of depression symptoms, defined using the 11-item Center for Epidemiologic Studies Depression (CESD) scale. We categorized participants into one of four groups based on their 21-year longitudinal pattern of elevated (≥3 mg/L) versus low (<3 mg/L) CRP (stable low; unstable low; unstable elevated; stable elevated). Analyses excluded participants with suspected depression during midlife.

Results: A total of 4,614 participants were included (age at CESD assessment: 75.5 [SD: 5.1]; 59% female; follow-up time: 20.7 years [SD: 1.0]). Compared to participants who maintained low CRP levels (stable low), participants who had elevated CRP at two of three visits (unstable elevated; ß = 0.09; 95% confidence interval [CI]: 0.02, 0.17) and participants who maintained elevated CRP at all three visits (stable elevated; ß = 0.13; 95% CI: 0.05, 0.21) had greater depression symptoms as older adults, after adjusting for confounders. After excluding participants with late-life cognitive impairment, only participants with stable elevated CRP demonstrated significantly greater late-life depression symptoms. In a secondary analysis, stable elevated CRP was associated with increased risk for clinically significant late-life depression symptoms.

Conclusion: Chronic or repeated inflammation in the decades leading up to older adulthood is associated with late-life depression, even in the context of normal cognition.