Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study

Abstract

The large burden and coexistence of physical disability, cognitive impairment, and depression in the oldest old makes summary markers of global functioning of great value, allowing for risk stratification. Inflammation may be a common underlying cause or represents a final common pathway. The present study investigated the association between elevated serum inflammatory markers and global functioning and its underlying aspects. A representative sample of 415 communitydwelling elderly subjects participating in the BELFRAIL study, with a mean age of 85 years, was included in the present analysis. Data on physical performance, dependence, and mental aspects of functioning and serum levels of 15 inflammatory proteins, including cytokines, chemokines, and acute-phase proteins, were assessed. Interleukin (IL)-6 was negatively associated with global functioning (odds ratio (OR) 4.35). The odds ratios for C-reactive protein (CRP) (OR 2.37) and the combined score of IL-6 and CRP (OR 2.59) were lower or not significant. IL-6 was significantly associated with physical dependence and cognitive function, and only a highly elevated serum level was associated with physical performance. Physical dependence was associated with a highly elevated CRP serum level. The proportion of functionally impaired older persons with elevated IL-6 was 81.93 %, giving a low positive predictive value (0.38), but a high negative predictive value (0.87). So, IL-6 is strongly associated with global functioning and all of the individual aspects of functioning, except suspected depression, in communitydwelling persons 80 years and older.

Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study

“…These results suggest that inflammation precedes depression, at least with regard to the cognitive symptoms of depression. However, we could not establish such a cross-sectional (Adriaensen et al 2014) or longitudinal association with the occurrence of GDS-15 screen-positives in our oldest old. A possible explanation for our result could be our low number of newly detected depression cases and short follow-up period to detect new cases.…”

“…Three consecutive models including an increasing number of covariates were used: unadjusted (model 1); a d j u s t i n g fo r a g e, g e n d e r, a n d C h a r l s o n Comorbidity Index (model 2); and adding institutionalization, BMI, and use of anti-inflammatory medication (model 3). Potential confounders were based on the bivariate analysis and our previous work (Adriaensen et al 2014). Predicted probabilities for the ordinal global functional decline variable were calculated after fitting the third model with quintiles of the serum IL-6 levels.…”

“…Details of the study's physical parameters were published previously (Adriaensen et al 2014). A significant decline in the physical summary performance scale, ranging from 0 to 14, was calculated with the formula (T0 −T1)*100/T0.…”

“…Details of the study's mental parameters have been published previously (Adriaensen et al 2014). As described above, the Edwards-Nunnally index was used to calculate a significant change in cognitive function based on the MMSE score.…”

“…Based on our previous definition of global functional impairment (Adriaensen et al 2014), the sum of the binary scores of the four aspects of physical and mental decline created an overall score of global functional decline. Participants were identified as having stable functioning (0), limited decline (1), or global functional decline (2-4) ( Fig.…”