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The 2006 Dennis W. Jahnigen Scholars Career Development Abstracts
Christopher Carpenter, MD
Pablo Celnik, MD
Gregory S. Cherr, MD
Ellen Flanagan, MD
Fredric Hustey, MD
Jason Johanning, MD
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John Schweinfurth, MD
Neil A. Segal, MD
Julie Ann Sosa, MD
Benjamin Sun, MD
Zhongcong Xie, MD, PhD |
 Christopher Carpenter, MD, Washington University at St. Louis, St. Louis, MO
Dr. Carpenter holds a Bachelors degree in Science from Hope College where he graduated cum laude. He graduated from Wayne State University School of Medicine before fulfilling a military commitment with the United States Navy as a Diving Medical Officer. In 1998 he began a five year residency in Emergency Medicine and Internal Medicine at Allegheny General Hospital in Pittsburgh, serving as a dual chief resident during his final year. In 2003, he joined the faculty of Emergency Medicine at the Washington University in St. Louis with primary clinical duties at Barnes-Jewish Hospital. His interest in older adult emergencies led him to a presidential appointment with the Society for Academic Emergency Medicine Geriatric Task Force to develop a didactic consensus conference for the 2007 scientific assembly. He was also selected as the Emergency Medicine content expert for the American Geriatrics Society's (AGS) Research Agenda Setting Process which outlines specialty-specific study and funding priorities within surgical subspecialties. In 2006, he was named a Jahnigen Career Development Scholar by the AGS providing two years of protected time and funding to study older adult abdominal pain. He has lectured locally and regionally on various issues related to emergency care of aging adults. Within his division he is the Journal Club director and has developed an interactive monthly program recently presented at the Emergency Medicine Counsel of Residency Directors as a model for the Practice Based Learning Core Competency. His Journal Club curriculum has also been rewarded with two local teaching awards and the Emergency Medicine Residents' Association Excellence in Teaching Award in 2006. The goal-directed Journal Club has garnered international attention as well when Dr. Carpenter was named as the only American faculty member of McMaster University's Best Evidence in Emergency Medicine course which has so far held courses in British Columbia, the Dominican Republic, and United Arab Emirates. Since January 2007, Dr. Carpenter has served as Senior Clinical Editor for Emergency Physician's Monthly and he was also recently named a Senior Reviewer for Pepid, a PDA-based EM tool. In order to help improve care for older patients visiting the Emergency Department, Dr. Carpenter has embarked on a project to design useful, highly sensitive tools called Clinical Decision Rules (CDR's) for abdominal pain. CDR's have not yet been designed solely for older adults. A CDR for elderly abdominal pain could prevent unnecessary hospitalizations or surgery and save lives.
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Non-Traumatic, Acute Abdominal Pain in ED Elderly, A Series of Systematic Reviews and A Clinical Consensus Conference |
Older adults continue to utilize emergency medical services at unprecedented rates. The demographic tsunami approaching the landscape of 21st Century medicine mandates an enhanced understanding of the diagnostic and prognostic impact various aspects of the history, physical exam, laboratory, and radiological evaluation possesses in making decisions during busy clinical shifts. The complex task of decision making includes the interweaving of out own clinical and personal experience, external rules and constraints, scientific evidence, and patient preferences. The frantic-paced, information-poor environment which is Emergency Medicine (EM) benefits from simple, highly sensitive tools called Clinical Decision Rules (CDR's) to utilize key components of the clinical evaluation to risk stratify patients and speed Emergency Department (ED) thoroughfare with out compromising patient safety or optimal outcomes. Designing useful CDR's necessitates the input of a multidisciplinary team to systematically and unequivocally define variables and clinically important outcomes. Although aging patients represent a disproportionate volume of admissions and overall ED resource consumption, CDR's have not yet been designed solely for older adults. A CDR for elderly abdominal pain could prevent unnecessary hospitalizations or surgery and save lives.
Emergency Medicine |
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Pablo Celnik, MD,Johns Hopkins University, Baltimore, MD 
Dr. Celnik is an Assistant Professor in the Department of Physical Medicine and Rehabilitation and the Medical Director of the Outpatient Neurorehabilitation Program at Johns Hopkins University. Since graduating from medical school, Dr. Celnik has developed a profound interest in the effects of aging on neuroplasticity and the mechanisms of recovery of function after brain lesions. Dr. Celnik's study will test the hypothesis that motor memory formation as a result of motor training is decreased in frail relative to non-frail older adults. The results of this study eventually will be applied to develop interventions geared towards reducing functional decline in older adults.
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Use Dependent Placticity in Frail Older Adults |
Aging results in a systemic decline of motor memory and physical performance. Training involving performance of simple repetitive thumb movements encodes a memory trace in the primary motor cortex that reflects the kinematic details of the practiced movements. This form of motor memory may represent a crucial step in the acquisition of complex motor skills, such as those used to perform activities of daily living (ADL), and likely a fundamental step in the process of recovery of motor function after brain lesions like stroke. The process of forming this type of motor memory has been extensively studied as a reliable and valid marker of use dependent brain plasticity (UDP). In healthy older adults, motor memory formation is decreased, but can be enhanced by different interventions. However, it remains unknown whether frail individuals have decreased ability to form motor memories when compare to non-frail older adults. It is possible that the systemic biological decline affecting frail individuals affects the ability to sustain UDP. In this proposal we plan to test the hypothesis that motor memory formation as a result of motor training is decreased in frail relative to non-frail older adults. To accomplish this we will conduct a case control study measuring the magnitude of motor memory formation as a result of simple motor training in frail and non-frail older adults using transcranial magnetic stimulation. We then plan to apply this new knowledge to more detailed biologic and physiologic studies of brain plasticity in this vulnerable subset of the older adult population and to develop specific rehabilitation interventions gear to reduce functional decline in older adults in general and frail in particular.
Physical Medicine & Rehabilitation |
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 Gregory S. Cherr, MD, State University of New York at Buffalo
Dr. Cherr is an Assistant Professor of Surgery and a Research Assistant Professor of Social and Preventative Medicine at State University of New York at Buffalo. Previously, he was at Wake Forest University School of Medicine, where he completed his general and vascular surgery training, as well as an NIH T-32 Training Grant in the Pathobiology of Vascular Disease Program. Dr. Cherr's interest in geriatric surgery grew out of his involvement in the daily care of older patients with vascular disease. While on the faculty at SUNY-Buffalo, he was an American College of Surgeons Health Policy Scholar and the co-investigator on a Donald W. Reynolds Foundation "UB Geriatric Center of Excellence" Grant. These experiences led him to focus his research on health-related quality of life (HRQOL) for patients with peripheral arterial disease (PAD). The aim of his proposal is to examine the associations between functional disability, chronic pain, depression, and HRQOL in elderly patients with PAD.
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Determinants of Health-Related Quality of Life in Patients with Peripheral Arterial Disease |
Peripheral arterial disease (PAD) affects 8-12 million Americans with an increased prevalence among the elderly. Patients with PAD have functional disability, chronic pain, and reduced health-related quality-of-life (HRQOL). However, the correlation between functional disability, chronic pain, and HRQOL is poor. For patients with PAD, other determinants of HRQOL must exist.
Patients with PAD have an increased prevalence of depressive symptoms and 36% of patients with severe PAD have depression. Chronic pain and functional disability may lead to depression, and depressed patients experience more chronic pain and functional disability. However, previous research on PAD and HRQOL has not included depression, and no systematic evaluation of HRQOL has been performed.
We hypothesize the relationship between PAD and HRQOL as conveyed by the following path diagram.
The specific aim of this proposal is to examine the associations between functional disability, chronic pain, depression, and HRQOL in elderly patients with PAD.
Subjects for this cross-sectional study will be elderly persons (age>65) recruited from outpatient clinics at two hospitals. Using validated questionnaires, the subjects will complete a single assessment of HRQOL, walking ability, depression, and chronic pain. Medications and other medical conditions will be recorded. Peripheral arterial disease will be diagnosed by ankle-brachial index and functional status will be evaluated with a 6-minute walk test.
Statistical analyses will include descriptive statistics, path analysis methodologies, and multiple linear regression. To demonstrate a meaningful dependence between PAD and HRQOL, 200 patients will be enrolled with 80% power to find a correlation as small as 0.197.
Peripheral arterial disease, a condition with considerable impact on HRQOL, affects 10% of adults over age 65. We have little understanding of the determinants of HRQOL for these patients. The proposed project will begin to address this problem and lay the ground work for potential interventions to improve HRQOL in patients with PAD.
General Surgery |
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Ellen Flanagan, MD, Duke University, Durham, NC
Dr. Flanagan is a Clinical Assistant Professor in the Department of Anesthesiology at the Duke University Heath System. While completing her residency, she became committed to preserving the dignity of patients at the end of life and felt that as a doctor she had an ethical obligation to this most vulnerable population. Her study seeks to provide elderly patients with outcome data specific to their surgical procedure prior to surgery that will assist them in determining how their final days, weeks, months will be spent.
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Postsurgical Outcomes of Elderly and Old Elderly Patients with DNR Orders |
Do Not Resuscitate (DNR) orders may be used as a marker for the sickest of elderly patients. These patients may choose to undergo palliative surgery when benefits outweigh the burdens of anesthesia, surgery and recovery. DNR orders in elderly surgical patients predict thirty-day postoperative morbidity and mortality, however, the course and therefore the burden of the thirty days prior to death is unknown. It is essential that elderly patients be provided with outcome data specific to their surgical procedure, prior to surgery that will assist them in determining how their final days, weeks or months will be spent. These patients should be offered surgical relief with the understanding that, if severe complications occur, they may choose to reduce the level of aggressive postoperative intervention and focus on palliation of symptoms.
We propose to build multivariable risk models to identify key preoperative characteristics and complications at forty-eight hours predictive of thirty-day postoperative morbidity and mortality in the elderly and old elderly. The National Surgical Quality Improvement Program (NSQIP) database should provide data necessary for development of these models. We will examine patient and family acceptance of these models in a small feasibility study.
Improved prognostication may better inform patients, families and physicians of likely postoperative complications. Preoperative discussion may allow elderly patients to voice preferences for acceptable types and duration of treatments prior to serious complications. Prior discussions of preferences may facilitate transition of care from aggressive postoperative to palliative care earlier in the intensive care unit stay thus providing care most consistent with the elderly patient's end of life goals.
These studies will be used to write an NIH proposal for a prospective, randomized controlled clinical trial evaluating an educational intervention that uses prognostic models to assist elderly patients and their families in making critical decisions prior to palliative surgery.
This proposal describes a series of studies that will generate data with immediate impact for geriatric patients confronting surgery at the end of life. These studies will also generate hypotheses that will be tested in future randomized controlled clinical trials.
Anesthesiology |
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 Fredric Hustey, MD, The Cleveland Clinic Foundation, Cleveland, OH
Dr. Hustey is an Assistant Professor and Staff Physician at the Cleveland Clinic Lerner College of Medicine, and a Fellow of both the American College of Emergency Physicians and the American Academy of Emergency Medicine. Shortly after graduating from his emergency medicine residency, Dr. Hustey began to develop an interest in the quality of care for older patients in the emergency department (ED) with delirium and dementia. He has served as principle investigator and published several studies on quality issues in geriatric emergency care. Dr. Hustey also has an interest in teaching, and is currently developing a curriculum for emergency medicine residents focusing on principles of geriatric acute care. His research, supported by the Jahnigen award, will examine electronic systems for health care information maintenance and transfer between skilled nursing facilities (SNF) and ED. He will test the hypothesis that communication between SNFs and the ED at the time of ED patient transition is improved after implementation of a standardized electronic transfer form.
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The Use of a Computerized System to Improve Information Transfer During Patient Transition from Skilled Nursing Facilities to the Emergency Department |
Background: At least one-fourth of patients residing in skilled nursing facilities (SNF) are transferred to emergency departments (ED) each year for evaluation. Accurate transfer of essential information, which is critical to optimal management of these patients in the ED, is often lacking. Hospitals and skilled nursing facilities (SNFs) are increasingly using electronic systems for health care information maintenance and transfer. Incorporating a standardized electronic method for information transfer into these pre-existing systems may be an effective way to improve communication during the ED transition.
Hypothesis: Communication between SNFs and the ED at the time of ED patient transition is improved after implementation of a standardized electronic transfer form.
Methods: Before and after study incorporating a standardized electronic transfer form into a pre-existing electronic discharge system (ECIN) used by many hospitals and skilled nursing facilities for discharge planning.
Participants: A consecutive sample of patients transferred from the largest subacute SNF affiliated with the Cleveland Clinic Foundation (CCF) to the CCF ED for evaluation.
Interventions: Implementation of a standardized electronic transfer form to communicate essential patient information to the ED at the time of the patient transition. This form will be incorporated into a pre-existing electronic discharge system that is used by many hospitals and SNFs and can be transmitted via secure internet connection to the ED.
Main outcome measurements: A scoring system is devised to measure communication of elements of critical information. One point is assigned for each element of critical information included during patient transfer (total of 9 elements with a maximum score of 9). Scores are assessed pre and post intervention via chart review. Additional outcomes include measurements of information transfer efficiency, impact of the intervention on markers of quality of care, and satisfaction of the ED and SNF staff with the information transfer process pre and post intervention.
Emergency Medicine |
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Jason Johanning, MD, University of Nebraska, Omaha, NE
Dr. Johanning is a Faculty Mentor Surgeon, the Director of Rural Surgery Outreach, and the Director of Surgical Geriatrics Education at the University of Nebraska Medical Center in Omaha. His interest in the geriatric patient developed through his work as a co-investigator in a multi-disciplinary Reynolds Grant to further geriatrics education at UNMC. Dr. Johanning realized that geriatrics education was a natural extension of his daily practice interacting with residents and medical students while treating patients with vascular disease. To address lower extremity peripheral arterial disease (PAD), Dr. Johanning will be focusing on abnormalities in gait. Through this research he hopes to educate his colleagues in vascular surgery, cardiology, and interventional radiology on optimal indications and outcomes for PAD patients.
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Evaluation of Gait Abnormalities in Geriatric Patients Induced by Peripheral Arterial Disease Utilizing Advanced Biomedical Measures |
PAD is a manifestation of atherosclerosis affecting nearly 12 million people living in the United States, most who are elderly. Every year 150,000 surgical procedures are performed for patients with advanced PAD. With the anticipated increase of our elderly population, PAD will continue to result in significant morbidity and mortality.
Caludication (Latin root word: "to limp") is the most common clinical manifestation of PAD where reduced blood flows results in limb heaviness, pain and ambulatory dysfunction. Despite obvious Dysfunction, very few reports have examined claudication as a primary gait or disability or impaired balance state. Even fewer reports have investigated the impact of improving blood flow on the parameters. These initial rudimentary gait and balance studies combined with our preliminary advanced biomechanical analyses suggest PAD produces significant gain and balance abnormalities. Unfortunately, the effects of surgical intervention on gait and balance of elderly patients with PAD are essentially unknown. The current study is based on two hypotheses; 1) Advanced biomechanical analyses can delineate the full spectrum of elderly PAD gait and balance abnormalities and 2) these abnormalities are reversed or attenuated by improving blood flow.
The specific aims are: 1) Delineate the full spectrum of gait and balance impairments incurred by elderly PAD patients. Patients will be evaluated using non-invasive vascular testing, lower extremity joint kinetics analysis, electromyographic assisted balance evaluation, and validated questionnaires to assess function. 2) Establish the efficacy of currently performed endovascular and open operation in improving gait and balance. Analyses will be repeated after therapeutic intervention. Response to treatment will then be ascertained.
A critical need exists to establish baseline impairment in elderly claudicants and determine optimal approaches for reversal of gait and balance abnormalities. It is our desire to capitalize on our unique multi-disciplinary approach to gait and balance abnormalities in the elderly PAD patient to answer these key questions.
General Surgery |
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 John Schweinfurth, MD, University of Mississippi, Jackson, MS
Dr. Schweinfurth is a Professor of Otolaryngology at the University of Mississippi Medical Center. Dr. Schweinfurth's geriatrics interest grew out of the study of age-related hearing loss and swallowing disorders. His commitment to geriatrics was further developed as he treated a large number of older adults who had lost their ability to eat safely due to stroke. Dr. Schweinfurth is currently evaluating the efficacy of a new modality to assist with swallowing therapy in the treatment of stroke victims and introducing interprofessional training for health professionals in the area of geriatric swallowing disorders.
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Assessment of swallowing Outcomes Following Neuromuscular Electrical Stimulation Therapy in Stroke Victims |
Mississippi has the highest incidence of cardiovascular disease and stroke in the U.S., and dysphasia is a common sequelae. Until recently, no good interventions were available for stroke victims to improve swallowing, and these patients largely became dependent on enteral feeding for sustenance and suffered from pneumonia due to aspiration. The proposed study has two parts: 1) to evaluate the efficacy of a new swallowing therapy in the treatment of stroke victims, and 2) to establish an interprofessional training program for health professionals in the area of geriatric swallowing disorders.
Swallowing therapy will be based on relatively new technology which employs electrical stimulation of neuromuscular structures of the tongue, neck, and larynx to improve swallowing function and has been shown to greatly decrease the time required to rehabilitate stroke victims to safe oral feeding. Because of the intensive therapy required, a projected 3 - 4 participants will be enrolled monthly at the time of initiation of rehabilitation. Participants will be randomized to immediate neuromuscular electrical stimulation therapy (NMEST) in addition to traditional dysphasia therapy (TDT), TDT followed by delayed NMEST, or TDT alone. Swallowing performance will be assessed by videoflouroscopic and/or endoscopic swallowing examinations before therapy and at intervals during treatment depending on progress. The primary outcome measure will be length of therapy required to achieve significantly improved performance on a dysphasia assessment scale or a steady-state.
The education program is intended to address the lack of formal training in swallowing disorders in otolaryngology residents as well as benefit speech language pathology graduate students. The interprofessional approach to education has been widely used in gerontology and provides a unique, effective, and comprehensive training experience that is adaptable to other fields. Training will consist of participation in a multidisciplinary team which treats swallowing disorders in a tertiary care center.
Otolaryngology |
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Neil A. Segal, MD, University of Iowa College of Medicine, Iowa City, IA
Dr. Segal is an Assistant Professor in the Department of Orthopaedics and Rehabilitation at the University of Iowa Hospitals and Clinics and the Medical Director for Amputee and Prosthetic Rehabilitation at the Veterans Affairs Medical Center in Iowa City, Iowa. As a physiatrist, Dr. Segal's long term goal is to reduce functional limitations in elders with osteoarthritis. In his study, he aims to assess functional limitations in elders with knee osteoarthritis through comparing three-dimensional motion analysis, capable of detecting compensatory forces and energy expenditures at unaffected joints. This will inform rehabilitation strategies to optimize function and reduce disability in elders with knee osteoarthritis.
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Enabling Elders with Knee Osteoarthritis Through Reducing Functional Limitations |
Older adults are at a high risk for disability and knee osteoarthritis is one of the most prominent causes. Prior studies have focused on increasing quadriceps strength in elders with knee inform rehabilitation strategies to optimize function and reduced disabilities in elders with knee osteoarthritis, but have not assess whether there are additional impairments contributing to these patient's functional limitations. The proposed research aims to assess for functional limitations in elders with knee osteoarthritis through comparing three-dimensional motion analysis, capable of detecting compensatory forces and energy expenditures at unaffected joints. The will inform rehabilitation strategies to optimize function and reduced disability in elders with knee osteoarthritis.
Physical Medicine & Rehabilitation |
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 Julie Ann Sosa, MD, Yale University School of Medicine, New Haven, CT
Dr. Sosa is an Assistant Professor of Surgery and Clinical Epidemiology in the Section of Oncologic and Endocrine Surgery at the Yale University School of Medicine. Dr. Sosa's particular interest as an endocrine surgeon is primary hyperparathyroidism (pHPT). As a researcher, she has worked to establish ties with a broad range of colleagues outside of her surgical discipline. Dr. Sosa's multidisciplinary randomized controlled trial will focus on psychological and cognitive problems in asymptomatic elderly adults with pHPT in an effort to gain a better understanding of the natural history of the neuropsychological findings associated with pHPT, and clarify the role of early surgery, especially MIP, in older patients with asymptomatic pHPT.
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A Multi-Institutional Randomized Controlled Trial Measuring the Effects of Surgery on Depression, Memory and Concentration Among Elderly Patients with Asymptomatic Primary Hypothyroidism |
Primary hyperparathyroidism (pHPT) is a common disease among the elderly associated with elevated serum calcium and parathyroid hormone (iPTH) levels. Its signs and symptoms range from serum biochemical abnormalities, to loss of energy, body aches, kidney stones, pancreatitis, and osteoporosis. Parathyroidectomy can cure pHPT in 98% of patients and significantly improve some symptoms. Depression and memory difficulties are believed to be part of the symptom complex, but there is a paucity of evidence addressing prevalence and optimal treatment. Our pilot data from 19 elderly subjects with pHPT referred for surgery revealed higher depression scores and greater spatial memory deficits when compared to age-matched patients with benign euthyroid thyroid disease referred for thyroidectomy. One month after surgery (using minimally invasive [MIP] or traditional parathyroidectomy), depression scores and spatial memory deficits were significantly improved when compared with thyroidectomy patients.
Our multidisciplinary randomized controlled trial will focus on psychological and cognitive problems in asymptomatic elderly patients with pHPT. We will randomize 60 patients with pHPT to medical follow-up or early surgery using MIP. We will evaluate all patients from a psychiatric standpoint using standard instruments, and from a cognitive perspective using verbal and novel, validated spatial memory tests, as well as evoked response potentials. Patients randomized to medical follow-up will be evaluated at baseline and at 6 month intervals for two years or until they become symptomatic. Patients randomized to surgery will be evaluated pre- and post-operatively at 3 and 6 months, and then at 6 month intervals for two years. Serum calcium, iPTH, creatinine, and urinary calcium will be obtained and correlated. Bone density will be evaluated annually. This study will lead to a better understanding of the natural history of the neuropsychological findings associated with pHPT, and clarify the role of early surgery, especially MIP, in elderly patients with asymptomatic pHPT.
General Surgery |
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Benjamin Sun, MD, MPP, Geffen School of Medicine at UCLA, Los Angeles, CA
Dr. Sun is an emergency physician and a UCLA Assistant Professor in residence at the West Los Angeles Veterans Affairs Greater Medical Center. His interest in geriatric issues was stimulated by his observation that current emergency departments are poorly designed for the unique needs of the elderly. Dr. Sun believes that developing research to improve geriatric emergency care will have an important public health impact. With support from the Jahnigen program, Dr. Sun will conduct research into geriatric syncope. The project will describe the short term epidemiology of serious clinical events in a large managed care cohort of older patients with syncope. A risk prediction instrument will identify patients at 'low risk' of short-term, serious clinical events. The ultimate goal of this research is to safely reduce hospitalization of older patients who present with syncope.
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Identification of "Low Risk" Older Patients with Syncope |
Geriatric syncope is a high-risk, emergency department presentation that may herald life-threatening conditions, and asymptomatic patients are frequently hospitalized for diagnostic evaluation. However, current admission patterns are characterized by low diagnostic and therapeutic benefit, potential for iatrogenic injury, and high costs. A prediction instrument to identify older patients at low risk of developing 30-day dangerous clinical outcomes, including death, arrhythmias, myocardial infarction, pulmonary embolism, aortic dissection, stroke, internal hemorrhage, and major traumatic injuries, may safely reduce hospitalizations and improve clinical outcomes.
Using a nested case-control research design, we propose to study a large, managed care cohort of older patients who presented with syncope to an emergency department with the following Aims:
Describe the frequency, timing, and event type of predefined, dangerous clinical outcomes occurring 30 days after an emergency department visit for syncope in patients over age 60
Derive a prediction instrument to identify patients over age 60 at low risk of developing a predefined, dangerous clinical outcome within 30 days of an emergency department visit for syncope
Our research team includes nationally recognized clinical scientists with specific skills in prediction instrument research in the elderly and in large emergency department cohorts. Our partnership with a large, integrated health system with an electronic medical records system will allow us to study a large population of older patients and obtain complete outcomes data at low marginal costs. The proposed research will lay the foundations for a definitive, prospective validation study and a randomized trial to assess the effects of prediction instrument use on health resource use and clinical outcomes.
Emergency Medicine |
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Zhongcong Xie, MD, PhD, Harvard/Massachusetts General Hospital, Boston, MA
Dr. Xie is an Assistant Professor of Anesthesia at Harvard Medical School and an attending Anesthesiologist at Massachusetts General Hospital. At Mass General, Dr. Xie's keen interest in geriatric anesthesia developed as a result of his providing anesthesia care for patients with Alzheimer's disease (AD) having surgery. He has focused his neuroscience research on assessing the potential contribution of perioperative factors to AD. The goal of his research under the Jahnigen Award is to study the effects of anesthetics, e.g., isoflurane, on AD neuropathogenesis, including apoptosis and beta-Amyloid generation. This study will ultimately lead to the development of a better anesthesia care for aging and AD patients, as well as for prevention and treatment of AD.
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Anesthesia and Alzheimer's Disease |
Alzheimer's disease (AD) is one of the greatest public health problems in the U.S., and its impact will only increase with demographic changes anticipated in the coming decades. Genetic evidence, confirmed by neuropathological and biochemical studies, indicates that excessive -amyloid peptide (A ) generated from amyloidogenic processing of the -amyloid precursor protein (APP) and cellular apoptosis play fundamental roles in the AD neuropathogenesis. Recent studies indicated that anesthetics isoflurane and proposal can enhance the oligomerization and cytotoxicity of A . However, the effects of anesthetics on apoptosis, APP processing and A generation, the key aspects of AD neuropathogenesis, are entirely unknown. This gap of knowledge impedes the progress toward a better anesthesia care for aging and AD patients, as well as further understandings of AD neuropathogenesis. The goal of this proposal is to primarily assess the effects of anesthetics on APP processing, A generation and apoptosis. The anesthetics that can influence APP processing and A generation will be further studied to determine the molecular mechanisms underlying these effects, especially, the extent to which the anesthetics affect -secretase activity leading to changes in APP processing, and ultimately, A production. Finally, we will also assess the effects of anesthetics on APP processing, A generation and apoptosis in AD transgenic mice. Specifically, the anesthetics to be individually assessed are nitrous oxide, isoflurane, sevoflurane and desflurane. These studies should eventually facilitate the development of strategies for a better anesthesia care for aging and AD patients, as well as for prevention and treatment of AD.
Anesthesiology |
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