Federal Project Grant Summary

The National Institute on Aging (NIA) awarded The Trustees of Columbia University in the City of New York $2.4M through the Aging Research program (CFDA 93.866) to conduct research on the pathophysiological mechanisms underlying cognitive impairment (CI) in heart failure (HF) patients. The four-year project, initiated July 1, 2026 and concluding June 30, 2030, will deliver foundational scientific research aimed at identifying how neuronal ryanodine receptor type 2 (RYR2) dysfunction contributes to cognitive decline across both heart failure with reduced ejection fraction (HFREF) and heart failure with preserved ejection fraction (HFPEF) phenotypes. Specifically, the research will investigate whether leaky hippocampal RYR2—a calcium signaling defect also implicated in Alzheimer's and Huntington's diseases—represents a common pathological mechanism in HF-related cognitive impairment and whether upstream activation of the sympathetic nervous system, inflammatory signaling, and TGF-β1 pathways drive this RYR2 dysfunction.

The research will employ innovative investigational approaches across multiple HF disease models to elucidate the calcium dyshomeostasis mechanisms underlying CI in HF, with anticipated outcomes including mechanistic insights into cognitive dysfunction in cardiovascular disease, identification of potential therapeutic targets, and scientific knowledge applicable to developing preventive or disease-modifying treatments for cognitive decline in HF patients—a significant clinical challenge that impairs treatment adherence and self-management, particularly among elderly populations.