A bold new discovery from Feinstein Institutes researchers illuminates the root driver of vascular cognitive impairment (VCI), offering two promising paths for therapy. This work, published recently in Alzheimer’s & Dementia, identifies the misregulation of vasoactive neuropeptides—the key regulators of blood-vessel tone—as the fundamental cause of microvascular dysfunction that underpins VCI. The finding opens doors to both drug-based and lifestyle or device-based interventions aimed at restoring proper blood flow and protecting cognitive function.
Led by Chunyan Li, PhD, associate professor at the Institute of Bioelectronic Medicine, and with contributions from PhD student Willians Tambo of the Elmezzi Graduate School of Molecular Medicine, the team conducted extensive molecular profiling and behavioral testing in an animal model of chronic cerebral hypoperfusion, a condition that mirrors the reduced brain blood flow seen in people with VCI. They then tested two complementary strategies: supplementing with calcitonin gene-related peptide (CGRP), a potent vasodilator, and activating the body’s natural diving reflex to conserve oxygen. In both cases, neuropeptide signaling was balanced, cerebral microvessels remained open, and memory and learning showed meaningful improvement in the preclinical model.
“VCI is a widespread and devastating condition with no effective treatments currently available,” said Dr. Li. “By pinpointing neuropeptide imbalance as the primary trigger of microvascular damage, we not only reveal VCI’s underlying mechanism but also outline two clear approaches to reversing it.”
These results challenge prevailing theories that oxidative stress and inflammation initiate vascular dementia. Instead, impaired neuropeptide control and consequent vessel constriction appear to occur first, setting the stage for later amyloid buildup and tissue injury. Oxidative stress and inflammation may thus be downstream effects rather than the root causes of impaired cerebral blood flow.
Building on these insights, the team is developing a novel noninvasive bioelectronic therapy: trigeminal nerve stimulation to trigger the diving reflex and promote improved blood flow. Supported by the U.S. Department of Defense and funding from the 2023 Northwell Health Innovation Challenge, this approach is being explored in models of traumatic brain injury and ischemic stroke—conditions that increase the risk of VCI.
“There is an urgent need for deeper understanding and better treatment options for VCI and related neurological disorders,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes. “Dr. Li and her colleagues have taken a crucial first step by showing how VCI begins, laying the groundwork for the next generation of targeted therapies.”
These findings not only upend traditional ideas about the origins of vascular dementia but also chart a clear course toward interventions that directly alter disease progression by restoring microvascular function and preserving cognitive health.
About the Feinstein Institutes
The Feinstein Institutes for Medical Research host Northwell Health’s research efforts and comprise more than 50 laboratories, thousands of clinical studies, and a large team of researchers and staff. The Institutes lead in bioelectronic medicine, behavioral science, cancer research, health system science, molecular medicine, and translational research, and publish two open-access journals: Molecular Medicine and Bioelectronic Medicine. Through the Elmezzi Graduate School of Molecular Medicine, an accelerated PhD program is offered. For more information about the work and ongoing studies, visit the Feinstein Institutes website and follow their updates on LinkedIn.
More News From The Feinstein Institutes for Medical Research
Back to Newsroom
