# Elucidating the molecular mechanisms of cognitive decline in atrial fibrillation

> **NIH NIH R03** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $81,000

## Abstract

PROJECT SUMMARY
The proposed R03 Small Grant Program for NHLBI K08 Recipients will enable my further
development into an established and independent researcher with expertise on elucidating the
mechanisms of cognitive decline in atrial fibrillation (AF) and enable me to understand the vascular
changes in the blood vessels and brain due to AF. I am a clinical cardiologist, cardiac
electrophysiologist, as well as an experienced basic and translational researcher whose long-term
goal is to understand the electrophysiologic causes of AF and to develop new therapies for the
treatment of cognitive and vascular dysfunction due to AF. I have a long-standing, productive
relationship with my mentor, Dr. Steven Marx, an experienced ion channel researcher, with whom I
published a novel mouse model, transgenic mice expressing human F1759A-NaV1.5 channels
crossed with mice expressing reverse tet-transactivator (rtTA) protein, which exhibit spontaneous and
sustained AF. We have demonstrated that these mice, akin to patients with AF, develop cognitive
impairment. We propose to study whether increasing AF burden is associated with vascular
dysfunction and if AF induced cognitive dysfunction is reversible with reduction of AF burden. I have
arranged a multidisciplinary board of established investigators (Dr. Scott Small and Dr. Mu Yang,
neurobiologists at Columbia University), to help me attain the goals of (1) comprehensive cognitive
training to phenotype a mouse model of cognitive impairment due to AF, (2) acquiring skills in
molecular cardiology and neurobiology to study possible therapies to reverse cognitive dysfunction,
and (3) understanding the mechanisms in which AF alters brain vascularization. I plan to use data
and skills acquired during this award to develop new therapies to treat cognitive dysfunction due to
AF and obtain the data necessary for an R01 submission.

## Key facts

- **NIH application ID:** 9915970
- **Project number:** 5R03HL146881-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Elaine Y Wan
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $81,000
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9915970

## Citation

> US National Institutes of Health, RePORTER application 9915970, Elucidating the molecular mechanisms of cognitive decline in atrial fibrillation (5R03HL146881-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9915970. Licensed CC0.

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