T‐Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Residents

Abstract

Objectives To determine whether immune phenotypes associated with immunosenescence are predictive of frailty and mortality within 1‐year in elderly nursing home residents. Design Cross sectional study of frailty; prospective cohort study of mortality. Setting Thirty‐two nursing homes in four Canadian cities between September 2009 and October 2011. Participants Nursing home residents aged 65 and older (N = 1,072, median age 86, 72% female). Measurements After enrollment, peripheral blood mononuclear cells were obtained and analyzed using flow cytometry for CD4⁺ and CD8⁺ T‐cell subsets (naïve, memory (central, effector, terminally differentiated, senescent), and regulatory T‐cells) and cytomegalovirus (CMV)‐reactive CD4⁺ and CD8⁺ T‐cells. Multilevel linear regression analysis was performed to determine the relationship between immune phenotypes and frailty; frailty was measured at the time of enrollment using the Frailty Index. A Cox proportional hazards model was used to determine the relationship between immune phenotypes and time to death (within 1 year). Results Mean Frailty Index was 0.44 ± 0.13. Multilevel regression analysis showed that higher percentages of naïve CD4⁺ T‐cells (P = .001) and effector memory CD8⁺ T‐cells (P = .02) were associated with a lower mean Frailty Index, whereas a higher percentage of CD8⁺ central memory T‐cells was associated with a higher mean Frailty Index score (P = .02). One hundred fifty one (14%) members of the cohort died within 1 year. Multivariable analysis showed a significant negative multiplicative interaction between age and percentage of CMV‐reactive CD4⁺ T‐cells (hazard ratio = 0.87, 95% confidence interval = 0.79–0.96). No other significant factors were identified. Conclusion Immune phenotypes found to be predictive of frailty and mortality in this study can help further understanding of immunosenescence and may provide a rationale for future intervention studies designed to modulate immunity.