The inverted CD4:CD8 ratio is associated with cytomegalovirus, poor cognitive and functional states in older adults

Background: Some premature features of immunosenescence have been associated with persistent viral infections and altered populations of T cells. In particular, the inverted T CD4:CD8 ratio has been correlated with increased morbidity and mortality across different age groups. Objective: Here, we investigated the role of persistent viral infections, cognitive and functional states as predictors of inverted CD4:CD8 ratio of older adults in a developing country. Methods: Three hundred and sixty community-dwelling older adults (aged 60-103 years) were recruited. Cognitive function was evaluated by the Instrument of Brief Neuropsychological Assessment and Mini-Mental State Examination inventory. Functional Activities Questionnaire was used to determine activities of daily living. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) serologies were determined by ELISAs. Peripheral blood was assessed for lymphocyte subsets by flow cytometry (CD4+, CD8+, NK, NKT, B and CD8+CD28-). Results: Fifty-nine individuals were identified with CD4:CD8 ratio <1, and had increased IgG titers to CMV (p < 0.01), but not to EBV, compared to subjects with CD4:CD8 ratio >1. The older adults with inverted CD4:CD8 ratio had impairments in some cognitive dimensions and had more functional disability and dependency (p = 0.01) than subjects with CD4:CD8 ratio >1. The lymphocyte subsets did not vary between groups. The increased CMV-IgG titers alone contributed to 8× higher chance to invert CD4:CD8 T cell ratio (OR 8.12, 95% CI 1.74-37.88, p < 0.01). Conclusion: Our data further indicate the role of CMV on circulating T cells, poor cognition and functional disability/dependency during aging.