# Role of Peripheral Immune Cells in Cognitive Aging: The Framingham Offspring Study

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $770,528

## Abstract

Cognitive health is central to successful aging, independence and well-being. The prevalence of dementia is
increasing in the U.S. and there are no effective therapies to prevent cognitive decline or to treat Alzheimer's
disease (AD) and related dementia. Neuroinflammation, including systemic immune cells, contributes to
neurodegeneration in AD and age-related dementias. Convincing evidence from animal models of AD, large
human genetic association studies of AD and dementia imaging markers, and small human case-control
studies of AD, demonstrate a role for immune cells and processes in the disease. The complex relationships
among the peripheral immune system, cardiovascular disease and its risk factors, and cognitive health are not
yet understood. Understanding the biologic mechanisms connecting circulating immune cells and cognitive
aging holds the potential to identify new blood based biomarkers and novel therapies for cognitive decline,
dementia and AD. We propose a comprehensive investigation of the role of circulating immune cells across the
spectrum of cognitive aging in the community-based Framingham Offspring cohort. The cohort is deeply
phenotyped for cognitive outcomes, including longitudinal dementia surveillance and repeated neuro-
psychological (NP) tests and brain MRI. We hypothesize that we will identify novel associations between
immune cell phenotypes in the pro-inflammatory and regulatory pathways and incident adverse cognitive
outcomes including development of clinical dementia, mild cognitive impairment (MCI), and measures of
cognitive aging defined by NP testing and brain MRI scans. We will investigate whether vascular factors
associated with immune cell phenotypes mediate the relationships, as vascular factors increase susceptibility
to cognitive aging. We will test our hypotheses with the following Specific Aims:
Aim 1: To profile circulating immune cell phenotypes in a dementia and stroke free community based sample
of men and women across a wide age range (n=1000, mean age 63, range 40 to 88) and identify cross-
sectional correlates of the immune cell phenotypes including age and sex.
Aim 2: To identify circulating immune cell phenotypes in the pro-inflammatory and regulatory pathways that
are risk factors for incident cognitive aging outcomes (dementia including AD and cognitive aging measures
based on NP testing and MRI brain volumes). We will test whether associations differ by sex and genetic risk.
Aim 3. To investigate whether the cognitive-outcome related immune cell phenotypes identified in Aim 2 are
associated with vascular factors known to increase susceptibility to cognitive aging including incident
cerebrovascular disease, cardiovascular disease and vascular risk factors.
This work will uncover novel mechanistic insights into the relations between circulating immune cell
phenotypes and the aging brain, identify new biomarkers for cognitive decline, and may reveal novel
therapeutic targets to prevent and treat d...

## Key facts

- **NIH application ID:** 10140262
- **Project number:** 5R01AG067457-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Margaret F. Doyle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $770,528
- **Award type:** 5
- **Project period:** 2020-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140262

## Citation

> US National Institutes of Health, RePORTER application 10140262, Role of Peripheral Immune Cells in Cognitive Aging: The Framingham Offspring Study (5R01AG067457-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10140262. Licensed CC0.

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