# Stress Mental Disorders Accelerated Aging and Dementia a 35 year Cohort Study

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2020 · $374,398

## Abstract

Numerous studies demonstrate links between depressive symptoms or disorders and poor cognitive and
functional outcomes. Anxiety symptoms and disorders, poor sleep, and stressful life events are common and
correlated with depression, but little is known about their association with cognitive and functional decline, such
as occurs in Alzheimer's disease (AD). These stress-related exposures are also associated with medical
morbidity and disability, but the mechanisms linking them to poor health outcomes are unclear. Cross-sectional
studies suggest that these exposures might lead to these outcomes by hastening cellular aging, measured by
shortening of telomeres. Prospective studies in cohorts with well-characterized histories of stress-related
exposures and repeated measures of cellular aging are needed to investigate this possibility. We propose to
analyze these issues using data already collected in the Baltimore Epidemiologic Catchment Area (ECA)
Followup Study cohort, adding another wave of data collection. The Baltimore ECA Study began collecting
structured diagnostic interview data on depressive and anxiety disorders in 1981 in a representative sample of
East Baltimore residents, and did so over three additional waves, most recently in 2004 (Wave 4). In addition
to measures of anxiety and depressive symptoms and disorders, the diverse (35% African American) ECA
cohort has completed repeated measures of poor sleep, life stressors, trauma exposure, cognition, and
functional impairment. In 2004, when all participants were aged ≥40 years, they donated blood and buccal
samples. All ECA subjects are now aged ≥50 (estimated mean = 68, range 52-96). We will locate and interview
an estimated 601 participants from Wave 4, repeating structured diagnostic interview assessment of mental
disorders, and measuring life stressors, trauma exposure, and poor sleep by both self-report and wrist
actigraphy. Participants will complete neuropsychological tests and functional measures, and will again donate
blood and buccal samples. This will enable us to determine the association of 35-year histories of stress-
related exposures, from mid to later life, with cognitive and functional decline, adjudicated mild cognitive
impairment and dementia diagnoses, including probable and possible AD, and biomarkers of cellular aging:
shortening of telomeres and increases in p16ink4a levels from 2004 to 2016. We will also determine if these
exposures are associated with epigenetic modification of genes in the ECA that we select based on novel
genome-wide association and methylation analyses we will conduct in existing data from the Baltimore
Longitudinal Study of Aging (BLSA) and the InCHIANTI cohorts. We will examine whether methylation of these
candidate sites, and measures of inflammation (measured in blood in 2004 and 2016) in the ECA, mediate
hypothesized predictive associations in the ECA cohort. Results will clarify the link between stress-related
exposures from mid to late...

## Key facts

- **NIH application ID:** 10160389
- **Project number:** 3U01AG052445-05S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** WILLIAM W EATON
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $374,398
- **Award type:** 3
- **Project period:** 2016-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160389

## Citation

> US National Institutes of Health, RePORTER application 10160389, Stress Mental Disorders Accelerated Aging and Dementia a 35 year Cohort Study (3U01AG052445-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10160389. Licensed CC0.

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