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.

Keywords: frailty; immune biomarker; immunosenescence; mortality; nursing home.