# Assessing the role of cerebrovascular brain injury and dysfunction in Alzheimer’s disease pathogenesis in the BEACoN Cohort

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $2,561,798

## Abstract

PROJECT SUMMARY
A critical gap in understanding the etiology of sporadic Alzheimer's disease (AD) is identifying the upstream
factors that lead to the development of both Alzheimer’s pathology and related neural dysfunction. Vascular
disease is found in approximately 80% of patients with concomitant AD pathology and thus may be an
important contributor to the development of AD, however relationships between vascular health and the
emergence of AD pathophysiology has not yet been comprehensively investigated in cognitively normal
samples. While large vascular adverse events such as stroke are known to confer risk for developing vascular
dementia, growing evidence suggests that subtle vascular damage accrued through a lifetime of injury could
predispose neural structure and function to become more susceptible to AD-related pathophysiology. Critically,
chronic and subtle forms of vascular disease are more commonly found in Black and Hispanic populations with
reduced access to healthcare and could help explain the increased prevalence of AD in these populations.
The goal of this renewal project is to establish the role of cerebrovascular injury and dysfunction (CVID) in the
pathophysiology of preclinical AD and develop individualized imaging-based cerebrovascular profiles that
predict memory decline across racially and ethnically diverse populations. We will conduct follow-up
assessments in 100 nondemented older adults (over 60 years of age) in our current award (BEACoN Cohort:
R01AG053555), which includes amyloid-PET (florbetapir), serial high-resolution MRI and tau-PET (MK-6240),
our innovative digital cognitive biomarkers which assess pattern separation, and a full UDS-3
neuropsychological testing battery. We will complement this with targeted new recruitment (n = 100) to
increase the representation of Hispanic/Latino and Black participants in our cohort. We have built an
infrastructure to radically transform recruitment and retention in our study including innovative partnerships with
clinical research organizations with a demonstrable track record in minority recruitment. Given focus on subtle
vascular damage, we will exclude based on history of stroke or severe cardiovascular disease. Our aims are
(1) Assess the novel biomarker framework in which CVID predicts tau accumulation, which predicts structural
and functional deterioration of the medial temporal lobes (MTL), subsequently predicting decline in
hippocampal pattern separation. (2) Construct individualized brain imaging based CVID profiles that
differentially predict decline in hippocampal memory across racially and ethnically diverse populations. (3) Aim
3: Associate CVID profiles with modifiable lifestyle risk factors and structural and social determinants of health
that are differentially distributed across racial and ethnic groups. In summary, we will develop a novel
mechanistic framework for how CVID contributes to AD pathophysiology and memory/cognitive decline that
directly addresse...

## Key facts

- **NIH application ID:** 10604863
- **Project number:** 2R01AG053555-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Michael A Yassa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,561,798
- **Award type:** 2
- **Project period:** 2017-08-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10604863

## Citation

> US National Institutes of Health, RePORTER application 10604863, Assessing the role of cerebrovascular brain injury and dysfunction in Alzheimer’s disease pathogenesis in the BEACoN Cohort (2R01AG053555-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10604863. Licensed CC0.

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