Peripheral immunosenescence biomarkers and longitudinal cognitive decline: a large population-based study
Rong Hua1,2, Aimin Yang3,4, Chun Sing Lam5
1School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China.
Npj Aging
|June 2, 2026
Summary
Higher CD8+ EMRA to Naïve T-cell ratios are linked to faster cognitive decline in aging adults. Maintaining balanced CD4:CD8 T-cell ratios may support cognitive health.
Area of Science:
- Immunology
- Neuroscience
- Gerontology
Background:
- Peripheral immunosenescence, or immune system aging, is increasingly linked to dementia.
- Specific lymphocyte subset roles in cognitive aging are not well understood.
- Large-scale longitudinal data on immunosenescence and cognition are limited.
Purpose of the Study:
- To investigate the longitudinal associations between T-cell immunosenescence metrics and cognitive decline.
- To examine the relationship between CD4:CD8, CD4+ EMRA:Naïve, and CD8+ EMRA:Naïve T-cell ratios and cognitive aging.
Main Methods:
- Utilized data from 7444 participants in the US Health and Retirement Study.
- Calculated three T-cell immunosenescence ratio metrics.
- Employed linear mixed models to assess 6-year cognitive decline associations, adjusting for covariates.
Main Results:
- An elevated CD8+ EMRA:Naïve ratio was significantly associated with accelerated cognitive decline.
- A nonlinear association was found for the CD4:CD8 ratio; intermediate levels correlated with slower decline.
- No significant association was observed for the CD4+ EMRA:Naïve ratio.
Conclusions:
- Immunosenescence metrics show compartmentalized associations with cognitive aging.
- Elevated CD8+ EMRA:Naïve T-cell ratios represent a specific detrimental pathway in cognitive decline.
- Balanced CD4:CD8 T-cell homeostasis may play a protective role in cognitive aging.
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