Dimitrios Kapogiannis, M.D.

Alzheimer's disease and related dementias (AD/ADRD) are characterized by a long preclinical phase with evolving and progressively irreversible pathology and failure of resilience mechanisms. Biomarkers reflecting both pathogenic and resilience mechanisms are essential for identifying patients at the preclinical stage, when disease-modifying interventions have the greatest chance of success. In addition, biomarkers can augment therapeutic discovery in AD/ADRD by helping select participants for precision clinical trials and as surrogate outcomes. An inherent limitation of blood biomarkers is their tenuous link to brain pathology, since they are often produced by multiple tissues and their brain-derived fraction has to cross multiple barriers. The Human Neuroscience Section has addressed this limitation for biomarker development in AD/ADRD by harvesting Extracellular Vesicles from blood and enriching them for neuronal and other brain cell origin. Neuronal-enriched Extracellular Vesicles can be used to probe and track pathogenic and resilience processes previously largely inaccessible in living humans, including neuronal-specific insulin resistance, mitochondrial dysfunction, and neurotrophin availability. In addition, the Human Neuroscience Section has been conducting early phase interventional studies targeting brain metabolism and resilience mechanisms to treat or prevent cognitive aging and AD/ADRD. The Section has conducted a Phase I study of a novel butyrylcholinesterase inhibitor called bisnorcymserine; a Phase IIa RCT of the GLP-1 receptor agonist exenatide in early AD; an RCT of 5-2 intermittent fasting in cognitively normal older individuals; and an RCT of an oral ketone ester in cognitively normal older individuals, assessing effects on brain health through Extracellular Vesicles, neuroimaging and Magnetic Resonance Spectroscopy, alongside cognitive performance and function. Currently, the Section is conducting an open-label, parallel-group, RCT called NECTAR (Neuroplasticity Enhancement from Cognitive Training Reinforced by Psilocybin) in cognitively healthy older adults and individuals with early-stage Alzheimer's disease.

Dimitrios Kapogiannis is a Behavioral Neurologist and Clinician-Scientist who specializes in Alzheimer's disease and related dementias (AD/ADRD). He acquired his Medical Degree from the National and Kapodistrian University of Athens, Greece, completed a Neurology residency training program at the Massachusetts General Hospital/Brigham and Women's Hospital/Harvard Medical School, and a Clinical Fellowship in Behavioral Neurology at the National Institute of Neurological Disorders and Stroke. He is currently a Senior Investigator at the National Institute on Aging conducting bench-side biomarker research and clinical studies in AD/ADRD. He also holds an appointment at the Johns Hopkins University School of Medicine Department of Neurology as adjunct Professor and provides clinical care at the Johns Hopkins Memory and Alzheimer's Treatment Center. He is widely recognized as an expert in the field of Extracellular Vesicles and has pioneered the development of neuronal Extracellular Vesicle-associated biomarkers for AD/ADRD and many neurological and psychiatric diseases. He has authored more than 200 peer-reviewed publications.