Helena Chang Chui received her MD from The Johns Hopkins University School of Medicine and completed her residency in neurology and fellowship in behavioral neurology at the University of Iowa Hospitals and Clinics. She is the author of more than 182 publications and has served on the editorial boards for Stroke, Alzheimer Disease and Associated Disorders and JAMA Neurology. Chui holds the Raymond and Betty McCarron Endowed Chair at the Keck School of Medicine and is internationally recognized for her research in Alzheimer disease (AD) and vascular cognitive impairment. She is the principal investigator for the National Institute on Aging-funded Alzheimer Disease Research Center, as well as a multi-institutional program project on vascular dementia. During the past 30 years, her research interests have focused on vascular contributions to cognitive impairment in late life. She has been particularly interested in non-occlusive pathways leading from vascular risk factors to vascular brain injury or AD pathology.

What initially attracted you to study Alzheimer disease and related disorders?

Looking back at the key turning points in my career, I can appreciate some intentional choices, a lot of opportunities, many wise and generous mentors, and a community of colleagues and patients. I think I inherited some of my best qualities from my parents, e.g., a strong work ethic from my father and a good dose of empathy from my mother. I chose medicine as the crossroads between science and service. My patients, who have faced incredible losses and hardship, have always kept me grounded.

I landed in neurology because I invited Antonio Damasio, MD, PhD, then at the University of Iowa, now at USC, to discuss schizophrenic “word salad,” and he generously invited me to train with him in behavioral neurology. Neurology focuses on the essence of human existence and experience, the workings of our brain and mind. What could be more exciting and fulfilling?

After finishing my residency in neurology and a fellowship in behavioral neurology, Leslie Weiner, MD, offered me a position as assistant professor at USC. He assigned me to Rancho Los Amigos Medical Center, where I joined an interdisciplinary geriatric program led by Bryan Kemp, PhD. Memory loss was the complaint du jour … and Alzheimer disease became the focus of my research.

In 1976, Robert Katzman, MD, then at the Albert Einstein College of Medicine, called national attention to the looming “silent epidemic” of Alzheimer disease. Both the United States and California legislatures responded by establishing a network of federal and state Alzheimer disease research centers. In 1984, under the inspired leadership of Caleb Finch, PhD, the Alzheimer Consortium of Southern California was awarded one of the first 5 NIA-funded Alzheimer Disease Research Centers. USC is also the home of two California Alzheimer Centers, led by Lon Schneider, MD, and Freddi Segal-Gidan, PhD. Thus, a period of combined federal and state funding fostered a generation of Alzheimer disease researchers, including my own.

The ADRC provides the opportunity to bring people together from many disciplines (basic science, translational scientists, clinicians, allied health professionals) to work together on the complex problems associated with Alzheimer disease. During the past 5 years, USC has strategically invested in Alzheimer disease, attracting world-class talent in vascular neurobiology with Berislav Zlokovic, MD, PhD; neuroimaging with Arthur Toga, PhD, and Paul Thompson, PhD; and clinical trials with Paul Aisen, MD. USC has become a veritable powerhouse in Alzheimer research.

Your research involves neuroimaging and neuropathological correlations. What influenced your decision to focus on this approach?

MRI imaging was just coming online as I started my academic career in 1981. The defining hallmarks of Alzheimer disease only could be detected by post-mortem autopsy. My mentor and department chair, Les Weiner, recommended that I combine behavioral neurology with another academic discipline, such as genetics, pathology or imaging. He also guided me to an NIH-funded career, starting with a K-award to study the nucleus basalis and locus ceruleus in Alzheimer disease with William Bondareff, MD, followed by an R01 to study the relationship between senile plaques and cerebral blood vessels at the electron microscopic level with Lynn Perlmutter, PhD.

By 1992, quantitative analyses of MRI scans were well underway. Building on talent distributed throughout the California Alzheimer Diagnostic and Treatment Centers, I became the principal investigator of the Aging Brain: Vasculature, Ischemic, and Behavior program project (P01 AG12435), a prospective, longitudinal study focused on the interactions between vascular factors and Alzheimer disease (1995 to 2015). The program project represented an interdisciplinary collaboration between investigators at USC; the University of California, San Francisco; the University of San Diego; UC Berkeley; and UCLA, who employed state of the art neuropsychological, neuroimaging and neuropathology methods to address the relationship between vascular and Alzheimer disease.

MRI provides a surrogate measure of disease progression and an outcome measure for clinical drug trials. Now amyloid and tau PET imaging provide an alternative method to detect the molecular signature of AD, namely amyloid plaques and p-tau neurofibrillary tangles. For a new fellow or faculty member interested in the disease of the 21st century, neuroimaging is a dynamic and timely scientific approach.

Could you share some of your group’s research findings?

The impact of subcortical ischemic vascular dementia (e.g., lacunar infarcts and white matter changes) on cognition is relatively modest, compared to the effects of AD pathology (Chui HC et al., Annals Neurol 2006; 60: 677). Both arteriosclerosis and AD contribute independently to cortical atrophy and cognitive impairment (Jagust W et al., Ann Neurol 2008; 63:72). However the relationship between atrophy and cognitive impairment differ in AD vs arteriosclerosis. For a similar degree of atrophy, AD is associated with much greater cognitive impairment than is arteriosclerosis (Zheng L et al., JCBM 2015). Higher levels of HDL-cholesterol and dodecohexanoic acid (DHA) are associated with less beta-amyloid accumulation on PET scan (Reed BR et al., JAMA Neurology 2014; 71:195; Villeneuve S et al., Neurology 2014; 83:40; Yassine et al., JAMA Neurology in press). These findings suggest that a healthy lipid profile might offer some protective effects against AD.

What advice do you have to junior faculty members to improve their competitiveness in getting research grants?

The distribution of effort typically changes over one’s academic career. In order to be successful as an independently funded investigator, a junior faculty member must devote 60-80 percent of their time to research, publishing, and writing grants. Another key ingredient is finding a supportive and successful mentor, who can provide guidance, make connections and open doors. Les Weiner advised me that it was our duty to serve on NIH study sections. Indeed, study section proved to be an invaluable, hands-on, training session on the finer aspects of writing grants. As Chair of the Department of Neurology, I have personally chosen more administrative and mentoring responsibilities, and am able to spend less time in research. However, within our vibrant academic community, I find great joy and meaning in fostering the research careers of the next generation of neurology residents and faculty.