Physician Investigator (Cl) Anesthesia, Critical Care and Pain Medicine, Mass General Research Institute

Henry Knowles Beecher Professor of Anaesthesia Harvard Medical School

Anesthetist Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital

MD 1985

PhD Wayne State University School of Medicine 1994

alzheimer's disease; amyloid beta-peptides; amyloid beta-protein precursor; anesthesia; anesthetics inhalation; caspase 3; cognition disorders; delirium; geriatric anesthesia; isoflurane; methyl ethers; neuropathogenesis; postoperative cognitive dysfunction

Research Areas

• Investigating the neuropathogenesis of Alzheimer's disease and postoperative cognitive dysfunction.
• Studying neurotoxicity of anesthetics and other perioperative factors, e.g., pain and sleep deprivation.
• Assessing cognitive function and postoperative delirium in humans.

Description of Research

Our own laboratory studies have suggested that perioperative factors such as hypoxia, hypocapnia, surgery, anesthetics, sleep deprivation and pain may contribute to neuropathogenesis of Alzheimer's disease (AD), postoperative cognitive dysfunction (POCD), and delirium.

Future projects in the Geriatric Anesthesia Research Unit in the Department of Anesthesia, Critical Care and Pain Medicine at MGH will explore the nature of the relationship between these perioperative factors and AD, work that may shed more light on AD neuropathogenesis; we will investigate the perioperative factors associated with POCD and attempt to establish a possible association between these factors and delirium.

Our work proceeds at both the cellular and molecular levels in cultured cells, neurons, mice and human subjects, and we employ such techniques as somatic gene transfer, genetic modification of animal models, RNA interference, RT-PCR, and immunocytochemistry; we also use various pharmacological tools and behavioral evaluations (e.g., Morris Water Maze and Fear Conditioning Test) when these are indicated.

These efforts may illustrate whether general anesthesia, surgery and other perioperative factors can initiate or accelerate the development of AD, POCD and delirium. The results of these studies will ultimately guide clinicians with regard to how to provide the safest anesthesia care for patients.