# Determinants of Alzheimer's Disease in Atrial Fibrillation apart from Stroke: The NOMINATE Study

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2022 · $260,905

## Abstract

PROJECT SUMMARY
Dementia poses a significant public health problem, and over 2 million American stroke survivors suffer from
dementia. Atrial fibrillation (AF), which is a particular type of irregular heartbeat, is the most common cause of
cardioembolic stroke, and studies have demonstrated that, among stroke patients, cardioembolic stroke
patients are at the greatest risk for cognitive decline. However, AF, even independent of clinical stroke, has
been associated with cognitive decline and dementia. The mechanisms linking AF and cognitive impairment
are likely multifactorial, but the cerebral pathology that underlies this independent pathway between AF and
dementia, apart from clinical stroke, is poorly understood. It is known that the cerebral pathology that leads to
dementia precedes the development of clinical symptoms, suggesting that such pathology may already be
present in patients with AF, but without prevalent dementia. Rapid developments in the dementia field have led
to the ability to use blood-based (plasma) biomarkers, rather than the previous, more invasive, techniques,
such as a lumbar puncture, to determine the presence of disease-causing pathology that contribute to the
development of clinical Alzheimer’s disease (AD). Such plasma biomarkers of AD pathology include
phosphorylated-tau181 (pTau181), plasma beta Amyloid (Aβ42/Aβ40) and neurofilament light (NFL), which
has been suggested as the three primary pathologic components (A/T/N; Amyloid/Tau/Neurodegeneration) by
which to guide AD-specific research. In this proposal, we aim to (Aim 1) compare the mean level of AD-
associated plasma biomarkers (p-tau181, Aβ42/Aβ40, NFL) in a cohort of stroke-free, non-demented, high-risk
cardiovascular (CVD) outpatients with AF to those in a control group of high-risk CVD patients without AF. We
also will determine the potential for differences in the levels of these biomarkers based on characteristics of the
AF patient, such as the type of AF a patient has or the possibility of an anticoagulation (AC) associated
treatment effect. Finally, (Aim 2) we will determine in a sub-set of those patients if AD associated brain atrophy
is present in CVD patients with AF versus in control patients without AF, accounting for silent cerebrovascular
disease. This proposal embodies the goals of the R21 high-risk, high-reward grant mechanism by representing
an innovative project that will begin to establish an understanding of the cerebral pathology in AF patients
underlying the associated risk for cognitive decline, distinct from prevalent clinical stroke. It also has the
potential for great public health impact by facilitating future research on potential targets to prevent, postpone
or treat AF-related dementia.

## Key facts

- **NIH application ID:** 10433238
- **Project number:** 1R21NS126967-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Michelle C. Johansen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $260,905
- **Award type:** 1
- **Project period:** 2022-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433238

## Citation

> US National Institutes of Health, RePORTER application 10433238, Determinants of Alzheimer's Disease in Atrial Fibrillation apart from Stroke: The NOMINATE Study (1R21NS126967-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10433238. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*