# Immunosenescence, socioeconomic disadvantage and dementia in the US aging population

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $756,321

## Abstract

While risk factors for cognitive decline and Alzheimer's Disease and related dementias (ADRD) have been
widely studied, there is still much unknown about the biological pathways that lead to ADRD. This project
seeks to improve our understanding of the pathophysiology of cognitive decline and ADRD by examining the
role of peripheral immunosenescence in these processes. A major gap in existing research is a lack of
longitudinal studies that can establish an etiologic link between peripheral immunosenescence and
development of incident ADRD. In addition, there are few population-based studies examining these processes
in U.S. representative samples. Population-based studies can evaluate whether clinical findings among ADRD
patients are generalizable to the broader population as well as examine the role of social determinants in these
processes. Despite consistently observed social inequalities in ADRD, including on the basis of race/ethnicity,
sex/gender, and socioeconomic status, the pathways by which social disadvantage lead to ADRD are not well
understood, limiting population-wide ADRD prevention strategies. Our long-term goal is to elucidate the role
of population immunity in predicting ADRD. The overall objective of the current proposal is to evaluate the
relationship between peripheral immunosenescence and domain-specific cognitive function, decline, and
ADRD diagnoses in a nationally representative sample of older US adults, and, to examine the extent to which
immunosenescence explains social inequalities in cognitive function, decline, and ADRD. Our central
hypothesis is that immunosenescence, characterized by an increased number of senescent immune cells
(e.g., CD8+CD45RA-, CD4+CD45RA-) and elevated inflammatory cytokines (C-Reactive Protein (CRP),
interleukin (IL)-6, TNF-alpha) will be associated with worse cognitive outcomes, and that immunosenescence
will partially explain some of the social inequalities in cognitive outcomes. The rationale for the proposed
research is that immunosenescence may be an important early risk factor for ADRD, potentially representing a
biological mechanism explaining population heterogeneity and inequalities in ADRD risk. To investigate these
relationships, we will pursue three specific aims:1) Determine the association between peripheral
immunosenescence and cognitive function and decline in the Health and Retirement Study (HRS); 2)
Determine the association between peripheral immunosenescence and incident ADRD measured both by HRS
cognitive assessment and linked Medicare claim data; and 3) Determine the extent to which
immunosenescence explains social inequalities in cognitive function, decline, and ADRD. This proposal is
innovative as it will be the first large-scale population-based study of immunity and cognition. It will yield
critical insights to our understanding of the pathophysiology of cognitive decline and ADRD, and inequalities in
these processes. This project is significant because the results c...

## Key facts

- **NIH application ID:** 10368271
- **Project number:** 1R01AG075719-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Allison E Aiello
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $756,321
- **Award type:** 1
- **Project period:** 2022-03-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368271

## Citation

> US National Institutes of Health, RePORTER application 10368271, Immunosenescence, socioeconomic disadvantage and dementia in the US aging population (1R01AG075719-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10368271. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*