# Earlier-Life Predictors of Midlife Risk Factors for Dementia: A 35-Year Follow-up Wallace Admin Suppl

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $105,550

## Abstract

Alzheimer’s disease (AD) and related dementias (AD/ADRD) are a public health crisis in the US
marked by growing racial disparities, with African Americans (AAs) two to three times more likely to be
diagnosed than non-Hispanic Whites. Efforts to identify modifiable earlier-life risk and protective factors
for known midlife risk factors for poor cognitive outcomes in later life are needed to protect the health of
middle-aged and older AAs. We propose to prospectively examine trajectories of stress exposures from
childhood to early midlife as predictors of known midlife risk factors for subsequent AD/ADRD in two
primarily (~66%) AA cohorts that are now ages 41-45 and have been followed repeatedly from age 6 to
age 32 (2009-2011) by the Johns Hopkins Prevention Intervention Research Center (PIRC). Relevant
individual- and community-levels stress exposures that occur from early life to middle adulthood
include: 1) adverse life circumstances (i.e., extreme poverty, residential instability, crime, incarceration,
racial discrimination, traumatic events); 2) mental disorders and their symptoms; and 3) poor sleep
(e.g., abnormal duration, fragmentation). Additionally, these stress exposures have been linked to other
risk factors for AD/ADRD, including obesity, hypertension, and diabetes, by which AAs are
disproportionately affected. We aim to determine the extent to which ~35-year trajectories of stress
exposures are associated with estimated midlife risk for later-life AD/ADRD, physiological aging
(telomere length, p16, methylation age), epigenetic modification, and inflammation, and cognitive
performance-all measured in early midlife-and if these associations are moderated by sex, race, and
AD/ADRD risk genes. We will also explore how the timing of exposures in the life-course affects these
associations, and if other potential moderators (e.g., childhood academic achievement,
educational/occupational attainment, alcohol/drug use, conduct problems, social support, perceived
control) affect these associations. We will further explore effects of two early-life (ages 6-8) PIRC
interventions on midlife study outcomes. To accomplish this, 1,150 PIRC participants will complete two
in-home interviews including a cognitive battery and actigraphic sleep assessments, and we will collect
biospecimens for genetic and epigenetic material and physiological aging measures. This study is a
rare opportunity to clarify links of earlier-life stress exposures with estimated midlife dementia risk,
identify vulnerable subgroups for targeted AD/ADRD prevention, elucidate the role of social inequities in
determining racial disparities in AD dementia, and establish a midlife cognitive baseline for future
follow-up of these unusually well-characterized longitudinal, primarily AA cohorts.

## Key facts

- **NIH application ID:** 11082723
- **Project number:** 3R01AG080829-02S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** GEORGE W. REBOK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $105,550
- **Award type:** 3
- **Project period:** 2023-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11082723

## Citation

> US National Institutes of Health, RePORTER application 11082723, Earlier-Life Predictors of Midlife Risk Factors for Dementia: A 35-Year Follow-up Wallace Admin Suppl (3R01AG080829-02S1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11082723. Licensed CC0.

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