Scholarly Expertise: Neurodegenerative disorders, dementia, Alzheimer's

Dani Dahyeon Kang

Dr. Dahyeon Kang is an Assistant Professor at the University of Washington School of Medicine. She earned her doctoral degree from the University of Illinois at Urbana-Champaign, where her work focused on the etiology of alcohol and substance use disorders through multimodal research methods, including alcohol administration, neuroimaging, transdermal biosensors, and ecological momentary assessments. At the University of Washington’s Department of Psychiatry, Dr. Kang investigates how individual and social factors interact to influence alcohol and cannabis use behaviors.

Randall Espinoza

I am currently the Medical Director at the Garvey Institute Center for Neuromodulation and am providing leadership to help grow our portfolio in the area of Neuromodulation and Interventional Psychiatry. Before coming to the UW, I was the Muriel Harris Chair of Geriatric Psychiatry and Professor of Clinical Psychiatry at UCLA. While at UCLA, I held many administrative, clinical and teaching leadership positions including serving as Medical Director of Inpatient Geriatric Psychiatry, Chief of Staff of the UCLA Neuropsychiatric Hospital, Founding Faculty of the UCLA Neuromodulation Division, Medical Director of the ECT and Interventional Psychiatry Program, among others.

I recently became Editor-in-Chief of the Journal of ECT and Related Therapies, the official publication of the International Society of ECT and Neurostimulation. My research projects have included investigating various neuromodulation and interventional therapies and developing novel educational programs and curricula. I have an abiding interest in mentoring and helping faculty at the start of their careers and a commitment to fostering the advancement of women and underrepresented minority (URM) faculty in academic medicine.

Daniel W. Fisher

My clinical and research interests center around behavioral and psychological symptoms that present in neurodegenerative diseases, especially dementias. Though dementia is well-known to affect one’s memory and cognition, over 90% of people with dementia develop new neuropsychiatric symptoms – including apathy, dysphoria. anxiety, aggression, agitation, disinhibition, hallucinations, and delusions. Despite the ubiquity of these symptoms, very little is known about how they develop in dementia. My research interests are in understanding more about the molecular and cellular mechanisms of neuropsychiatric symptoms in dementia beyond the well-studied changes associated with cognitive deficits.

Along with my research mentor Martin Darvas PhD (Department of Laboratory Medicine and Pathology), we employ numerous approaches to better understand these neuropsychiatric symptoms, including techniques involving transcriptomic analyses of human and mouse post-mortem tissue, development and implementation of biomarkers derived from human and animal model fluids (plasma, serum, cerebrospinal fluid), virally-mediated gene manipulations, animal modeling of cognitive and neuropsychiatric phenotypes, and basic cellular and molecular biology techniques.

Michelle Wiese

I am an Acting Assistant Professor in the Department of Psychiatry and Behavioral Sciences at the University of Washington. I received my MD, MPH from the University of Nebraska Medical Center and completed my adult residency at the University of Washington where I was chief resident. I then went on to complete a fellowship in Consultation-Liaison Psychiatry at the University of Washington. I am currently on faculty at Harborview Medical Center on the inpatient psychiatry unit and inpatient psychiatry consult service. I have a longstanding interest in the intersection between medicine and psychiatry and in working with people who suffer from serious mental illness and treatment-resistant conditions. I have clinical interests in ECT, psychopharmacology, co-morbid medical conditions, and adjunctive psychotherapies. I value caring for the whole person through thorough and accurate diagnosis, treating co-morbid medical conditions, and minimizing medications when possible. I have teaching interests in reducing stigma surrounding serious mental illness and educating residents and medical students about psychiatric care.

Laura Prater

Dr. Prater holds a doctorate in public health from the Ohio State University, with a focus in health services research, pragmatic intervention development and policy evaluation. Her work focuses on understanding the circumstances around firearm suicide among vulnerable populations and developing health systems interventions for suicide prevention through firearm safety. Using a public health lens, she works on tailoring interventions to meet the unique needs of vulnerable populations (e.g. dementia, terminal illness) at increased risk for suicidal thoughts and behaviors. She is currently funded by the National Institutes on Aging and the American Foundation for Suicide Prevention to produce clinical decision-making tools to help persons with early dementia, their care partners, and primary clinicians, to make safer plans for firearm storage.

Douglas Lane

I am a clinical psychologist with board certification in geriatric psychology.  I am based in the Geriatrics and Extended Care Service of the VA Puget Sound Healthcare System.

Eric Petrie

My work focuses on the diagnosis and treatment of post traumatic stress disorder (PTSD), mild traumatic brain injury (mTBI), and neurodegenerative dementias, as well as applications of positron emission tomography (PET) and other functional neuroimaging modalities to elucidating the pathophysiology of PTSD, mTBI, Alzheimer’s Disease, and other neurodegenerative dementias.

Gail Li

My research has focused on the clinical and epidemiological study of brain aging, Alzheimer’s dis-ease (AD), and, most recently, mild traumatic brain injury (mTBI).

The epidemiological study of aging and AD. Over the past 20 years, I have pursued studies investigating the putative risks and protective factors for AD in a large community-based longitudinal cohort known as Adult Change in Thought (ACT). I have used the ACT, which is led by Drs. Eric Larson and Paul Crane, to characterize the associations between an array of risk factors, ranging from cardiovascular traits to depression, and both the incidence of dementia and the neuropathological changes seen at autopsy. In collaboration with experts in environmental and occupational health, I am now co-leading an NIH-funded R01 study to investigate the adverse effects of air pollution on brain aging, cerebrovascular disease, and neurodegenerative diseases.

Using biomarkers to identify the preclinical stage of AD, understand brain aging, and assess out-comes in clinical trials. The neuropathological changes of AD begin decades prior to a clinical diagnosis of AD. In collaboration with Dr. Elaine Peskind at VA Puget Sound, I have investigated several established (e.g., Ab42) and novel (e.g., E-selectin) AD biomarkers in cerebrospinal fluid (CSF) as we seek a way to improve both the early diagnosis of AD and the differential diagnosis of dementing diseases. Leveraging a large biorepository bank at VA Puget Sound, we have studied several of these CSF biomarkers in a cohort of cognitively normal subjects, and through this work, we have shown that (a) high CSF concentrations of F2-isoprostane, a biomarker for oxidative stress, are associated with poor executive function, cigarette smoking, and elevated body mass index; and (b) reduced levels of CSF brain-derived neurotrophic factor, a protein critical to the organization of neuronal networks and synaptic plasticity, are associated with poorer memory and predict cognitive decline over the next 3 years. Finally, we have established the feasibility of using CSF biomarkers, such as phosphorylated tau, as surrogate markers for AD in clinical trials during the pre-clinical stage of AD.

Primary prevention for AD: From observational study to clinical trial. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase inhibitors, known as statins, decrease mortality from coronary heart disease and stroke. Our epidemiological studies found that the use of statins at relatively younger ages (e.g., prior to age 80) is associated with a decreased incidence of AD, especially in APOE ε4 allele carriers; statin exposure was also associated with fewer AD neuropathologies, especially in terms of neurofibrillary tangle burden. To provide further evidence of a potential protective effect of statins for AD, I recently completed a proof-of-concept, double-blind clinical trial in collaboration with Drs. Elaine Peskind, Eric Petrie, and Cynthia Mayer on the effects of simvastatin on CSF AD biomarkers in cognitively normal individuals. In that study, we found that simvastatin-related reductions in CSF p-tau181 concentrations may be dependent on low-density lipoprotein (LDL) cholesterol. To learn more, we will next investigate the potential disease-modifying effects of simvastatin on tau phosphorylation in persons with hypercholesterolemia.

mTBI research. Because neurodegenerative diseases like chronic traumatic encephalopathy (CTE) are the long-term consequences of repeated head injuries, I recently expanded my research interests to understand the risk of mTBI in combat Veterans with blast-related injuries for neurodegenerative diseases. To that end, I am an active member of a multidisciplinary research team at VA Puget Sound that seeks effective treatments for Veterans with mTBI. As a collaborator in this work, which is led by Dr. Elaine Peskind, I am striving to develop strategies to reduce the long-term sequelae of mTBI.

Jeff Iliff

Personal Statement

I focus on neurodegeneration and traumatic brain injury research at the VA Puget Sound and at the UW Alzheimer’s Disease Research Center.

My work has probed the ‘glymphatic’ system, a brain-wide network of perivascular spaces that facilitates the clearance of waste products, including amyloid beta and tau, from the brain interstitium during sleep. Previously at OHSU, my group demonstrated that the glymphatic system fails in the aging brain and in the young brain after traumatic brain injury. The studies suggest that impairment of glymphatic function may be one factor that renders the aging brain vulnerable to protein aggregation and neurodegeneration and may link brain trauma early in life with the development of dementia in the decades that follow. My ongoing work seeks to define the molecular and cellular underpinnings of impaired glymphatic function in the aging and post-traumatic brain, and to use novel MRI-based imaging approaches to extend these findings into clinical Alzheimer’s disease and post-traumatic populations.

As the leader of the ADRC’s new Research Education Component, I oversee the effort to train and develop a community of clinical, basic and translational Alzheimer’s disease researchers with the necessary clinical, scientific and technical competence to effectively collaborate to define the mechanistic and biological underpinnings of Alzheimer’s and related dementia, and to translate this understanding to improve the lives of those living with memory loss and dementia.

Olena Korvatska

Personal Statement

My research interests are focused on gene discovery and elucidation of molecular pathways underlying molecular mechanisms in cognitive decline caused by neurodegeneration and protein aggregation disorders. My current research projects involve both Mendelian (X-linked Parkinson and Spasticity) and complex disorders (such as Alzheimer’s disease). We analyze familial forms of diseases using exome sequencing and linkage mapping approaches. Candidate variants are validated using live patient cells and post-mortem tissue. Further functional insights are gained by generation of model cell lines and/or transgenic mice. The strategy allowed uncovering various disease mechanisms central to pathogenesis: protein misfolding and aggregation, deletion/duplication of genic regions and tissue-specific alternative splicing.