Cognitive Frailty is Associated With Elevated Proinflammatory Markers and a Higher Risk of Mortality

•What is the primary question addressed by this study?We evaluated if cognitive frailty is associated with increased proinflammatory status and higher mortality risk in older adults.•What is the main finding of this study?We found that older adults classified as having cognitive frailty have significantly higher levels of the proinflammatory cytokine IL-6. Also, we found that the cognitive frailty is an independent risk factor for mortality over 10 years of follow-up in older adults.•What is the meaning of the finding?Cognitive frailty is a potentially modifiable risk factor for premature mortality in older adults. Cognitive impairment and physical frailty are common among older adults and associated with a higher likelihood of adverse health outcomes. These two conditions frequently coexist in the same individual as cognitive frailty, yet few studies have examined the impact of such comorbidity on clinical outcomes or underlying biological mechanisms. A total of 1,340 older adults (age ≥60 years old) from the Bambui Cohort Study of Ageing, with a total follow-up of 10 years, were included in this study. Frailty was defined by the accumulation of deficit framework and cognitive impairment based on scores on the MMSE less than 22. In addition, serum IL-6 levels were measured by cytometric bead array assay. Individuals classified with cognitive frailty had significantly higher serum IL-6 levels compared to the robust, cognitively unimpaired group. Those with cognitive frailty (aOR = 1.97 [1.18–3.27] and prefrailty and cognitive impairment (aOR = 1.83 [1.24–2.69]) had the highest mortality risk over 10 years of follow-up. Higher IL-6 levels were also independently associated with a higher mortality rate (aOR = 1.37 [1.23–1.54]). Our study shows that cognitive Frailty indicates a vulnerability state and of increasing mortality risk. Our findings also suggested that proinflammatory abnormalities can be viewed as a central phenomenon underlying common age-related problems (e.g., cognitive impairment and Frailty) and outcomes (e.g., mortality).