# A Life Course Approach to Integrating Trauma and Cognitive Aging: A Cohort of 9/11 Responders

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $1,582,310

## Abstract

Abstract
Alzheimer’s disease (AD) caused more than 110,000 deaths in 2017 making it the sixth most common cause
of death. With an estimated lifetime risk of 40% in the U.S. population and an estimated cost of care exceeding
$200 billion, ADRD is burdensome for individuals and their families, and costly to society. While work is
increasingly determining risk and resilience factors for ADRD, little is known about causes of preclinical AD.
Life course researchers have posited that a lifetime of stressors can accumulate to cause increased incidence
of symptoms consistent with preclinical AD including changes to memory and early stages of cognitive
impairment. In creating the first and only cognitive monitoring study of World Trade Center responders
(R01 AG049953; PI, Clouston), we posited that chronic posttraumatic stress disorder (PTSD), a relatively
common disorder characterized by intrusive memories of past trauma accompanied by a heightened
stress response, might help to provide a unique mechanism linking lifetime stressors with later onset
of cognitive decline reminiscent of ADRD. Those data sought to examine the extent to which childhood
exposures, midlife exposures, genetic differences, and later-life changes in health would help to explain
cognitive symptoms of preclinical AD in World Trade Center responders. While we now understand that PTSD
predicts increased risk of cognitive and physical symptoms consistent with preclinical AD, the mechanisms of
action for this association remain opaque. In a recent pilot study, we found that WTC responders have
increased plasma neurofilament-light and plasma tau (which was associated with memory in this sample), and
also identified a strong association between PTSD and changes to plasma amyloid-b burden. We now posit
that PTSD may either cause an Alzheimer’s pathological cascade with one result being cognitive dysfunction in
domains of fluid cognition including memory. This study seeks to examine, using longitudinal data, the extent
to which PTSD might trigger an AD neuropathological cascade. However, since responders are very young to
be experiencing ADRD, we additionally hypothesize that PSTD may reduce cognitive reserve thereby
amplifying the effects of extant neuropathology. Finally, we propose an alternative hypothesis stating that
inhaled nanoparticulate matter exposures, which some responders reported while at the WTC may have
increased the burden of a known neurotoxin with one result being increased risk of neuropathological changes
including increased tauopathy.
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## Key facts

- **NIH application ID:** 10260411
- **Project number:** 5R01AG049953-07
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** SEAN CLOUSTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,582,310
- **Award type:** 5
- **Project period:** 2015-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260411

## Citation

> US National Institutes of Health, RePORTER application 10260411, A Life Course Approach to Integrating Trauma and Cognitive Aging: A Cohort of 9/11 Responders (5R01AG049953-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10260411. Licensed CC0.

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