Overview
My work uses translational neuroscience approaches, such as cerebrospinal fluid molecular assays, sleep EEG, cognitive testing, and delirium assessment to identify mechanisms of delirium. Delirium is a syndrome of disrupted attention and consciousness that occurs in ~20% of the >19 million older surgery patients and ~50% of the >5 million intensive care unit (ICU) patients in the United States every year. Delirium is also associated with increased risk for Alzheimer’s disease and related dementias (ADRD), yet there are no FDA-approved drugs to prevent it, due to a major gap in our understanding of its underlying mechanisms. Our current work aims to discover potential mechanisms of delirium that could be targeted in future studies. We have recently found that increased blood-brain barrier dysfunction is associated with postoperative delirium, but it is unknown what inflammatory mediators actually cross the disrupted blood-brain barrier to drive delirium. Using mass spectrometry proteomics, we are examining the relationship of proteins and inflammatory markers found in the cerebrospinal fluid 24-hours following surgery with postoperative delirium. We are also interested in strategies that potentially protect the blood-brain barrier following surgery. Since sleep disruptions can cause blood-brain barrier dysfunction, we are conducting a study to determine the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older surgical patients. Finally, we are working to extend these investigations to ICU patients, who are often more severely affected by delirium and more frequently develop long-term sequelae such as post-ICU long-term cognitive impairment (that is similar in magnitude to Alzheimer’s disease and related dementias).
Current Appointments & Affiliations
Recent Publications
Mind the messenger: role of extracellular vesicle signalling in postoperative neurocognitive dysfunction.
Journal Article Br J Anaesth · June 2025 Extracellular vesicles are secreted by virtually every cell and allow the transfer of bioactive molecules including proteins, nucleic acids, and lipids to other cell types across the body. This study of the role of extracellular vesicles and their cargo in ... Full text Link to item CiteCerebrospinal fluid proteome of patients with persistent pain and/or postpartum depression after elective cesarean delivery: An exploratory prospective cohort study.
Journal Article J Clin Anesth · June 2025 BACKGROUND: Persistent pain (>2 months) after cesarean delivery (CD) can affect up to 20 % of patients, and is associated with increased risk for postpartum depression (PPD). Preoperative identification of patients at risk for persistent pain and PPD remai ... Full text Link to item CiteErratum: The Role of Sleep Apnea in Postoperative Neurocognitive Disorders Among Older Noncardiac Surgery Patients: A Prospective Cohort Study.
Journal Article Anesth Analg · May 1, 2025 Full text Link to item CiteRecent Grants
The role of cerebrospinal fluid complement activation in delirium and post-intensive care unit long-term cognitive impairment
ResearchPrincipal Investigator · Awarded by National Institutes of Health · 2024 - 2029Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium risk and Inattention
ResearchPrincipal Investigator · Awarded by National Institute on Aging · 2022 - 2027Efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older surgical patients: A double-blinded, randomized, placebo-controlled trial
Clinical TrialPrincipal Investigator · Awarded by Merck Sharp & Dohme LLC. · 2023 - 2026View All Grants