Natalia Sonsin-Diaz1, Rebecca F Gottesman2, Elizabeth Fracica3, Jeremy Walston4, B Gwen Windham5, David S Knopman6, Keenan A Walker7. 1. Johns Hopkins University (NSD), Baltimore, MD. 2. Departments of Neurology and Epidemiology (RFG), Johns Hopkins University School of Medicine, Baltimore, MD. 3. Johns Hopkins University School of Medicine (EF), Baltimore, MD. 4. Division of Geriatric Medicine and Gerontology (JW), Center on Aging and Health, Johns Hopkins University, Baltimore, MD. 5. Department of Medicine (BGW), Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS. 6. Department of Neurology (DSK), Mayo Clinic, Rochester, MN. 7. Department of Neurology (KAW), Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: Kwalke26@jhmi.edu.
Abstract
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.
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.
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