Long‐Term Systemic Inflammation and Cognitive Impairment in a Population‐Based Cohort

Abstract

OBJECTIVES Evidence suggests inflammation is associated with cognitive impairment, but previous epidemiological studies have reported conflicting results. DESIGN Prospective population-based cohort. SETTING Epidemiology of Hearing Loss Study participants. PARTICIPANTS Individuals without cognitive impairment in 1998–2000 (N = 2,422; 1,947 with necessary data). MEASUREMENTS Cognitive impairment (Mini-Mental State Examination score <24 or diagnosis of dementia) was ascertained in 1998–2000, 2003–2005, and 2009– 2010. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) were measured in 1988–1990, 1998–2000, and 2009–2010; tumor necrosis factor-alpha was measured from 1998–2000. RESULTS Participants with high CRP in 1988–1990 and 1998–2000 had lower risk of cognitive impairment than those with low CRP at both time points (hazard ratio (HR) = 0.46, 95% confidence interval (CI) = 0.26–0.80). Risk did not differ according to 10-year IL-6 profile or baseline inflammation category in the whole cohort. In sensitivity analyses restricted to statin nonusers, those with high IL-6 at both times had greater risk of cognitive impairment than those with low IL-6 at both times (HR = 3.35, 95% CI = 1.09–10.30). In secondary analyses, each doubling of IL-6 change over 20 years was associated with greater odds of cognitive impairment in 2009–2010 in the whole cohort (odds ratio (OR) = 1.40, 95% CI = 1.04–1.89), whereas a doubling of CRP change over 20 years was associated with cognitive impairment only in statin nonusers (OR = 1.32, 95% CI = 1.06–1.65). CONCLUSION With data collected over 20 years, this study demonstrated greater likelihood of cognitive impairment in individuals with repeated high or increasing IL-6. The inconsistent CRP findings may reflect effects of statin medications, survival effects, or adverse effects associated with chronically low CRP. Further studies of long-term inflammation and cognitive impairment are needed.

Host factors associated with serologic inflammatory markers assessed using multiplex assays

“…74 A doubling of CRP levels has also been implicated in increased risk of hepatocellular carcinoma 75 and cognitive impairment. 76 In the present study, the median CRP level for men with normal BMI was 0.1 mg/L and was more than doubled for men with overweight and obese BMI (1.1 mg/L, and 2.2 mg/L, respectively). Current smoking and hypercholesterolemia were also associated with elevated CRP levels (PD = 53% and 28%, respectively).…”

The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging

“…In another study, it was reported that a higher intracellular cytokine production of IL-1β and IL-6 by activated monocytes was predictive of lower cognitive performance in working memory in healthy older individuals aged 55-70 years [106]. In a prospective population-based cohort study with data collected over 20 years, it was reported that higher serum CRP and IL-6 were associated with a likelihood of cognitive impairment [107]. These studies indicate that an increased risk of cognitive decline is associated with agerelated inflammatory disorders.…”

Waist circumference is correlated with poorer cognition in elderly type 2 diabetes women

“…In model 1, we controlled for age and years of education, well-established confounders for cognitive outcomes, and body mass index (BMI), a confounder for waist circumference. In model 2, we added potential confounders associated with dementia and/or central adiposity [2,6–12]: cardiovascular (HbA1c; creatinine; total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterols; triglycerides; and diastolic and systolic blood pressure), diabetes-related (duration in the Diabetes Registry and diabetes medication status: no medication, insulin only, hypoglycemic medication only, combination of insulin with hypoglycemic medication), APOE ε4 genotype, and inflammation (CRP and IL-6).…”