ANNUAL REPORT July 1, 2019 to June 30, 2020 1 Table of Contents Preface ........................................................................................................................ Page 3 Introduction to the Annual Report ........................................................................... Page 5 Institutional Information ........................................................................................... Page 12 - Research Summaries - Key Personnel Project Progress Reports ......................................................................................... Page 47 - Project Progress Reports by Institution 2019-2020 Publications, Manuscripts, & Grants - Publications and Manuscripts ........................................................................... Page 226 - Current and Pending Grants ............................................................................ Page 267 Scientific Abstracts .................................................................................................. Page 316 Institutional Budgets and Justifications ........................................... See companion report 2 Preface The COVID-19 pandemic is upon us, and it has had a profound impact on us all. It has already taken major tolls on our safety, well-being, economic stability, work and way of life. It has impelled us to find new ways to protect and address the needs of our patients, research participants and families, colleagues, communities and each other, avert an overwhelming healthcare program, and prepare for the challenges and uncertainties that lie ahead. It has led us to rearrange our clinical and research priorities and rise to the immediate challenges while finding ways to address our longstanding goals. It has called on us to do so from a social distance, yet do it together. Like others around the world, researchers, clinicians and organizations in the Arizona Alzheimer’s Consortium continue to respond to this rapidly responding crisis in ways that put everyone’s safety first, adhere to the social distancing precautions needed to dampen the virus’s spread, and reduce the chance that scarce healthcare resources will be overwhelmed. At the same time, we have sought to fulfill the stated objectives of the Consortium and its National Institute on Aging (NIA) supported Arizona AD Center (ADC) as much as possible. We have modified or temporarily suspended many studies, sought to communicate virtually with our patients, participants and families, and reserved in-person visits for those activities that are deemed essential to our stakeholder’s safety and well-being. Due to the social distancing precautions, we canceled the Annual Scientific Conference, which the University of Arizona was scheduled to host in May, we plan to conduct our annual External Advisory Committee Meeting virtually in June, and we sought and kindly received permission from the Arizona Department of Health Services (ADHS) to complete several projects after the standard June 30 deadline. Despite these precautions, we continue to make great progress, and we have included this year’s project progress reports and research abstracts, publications, and grants in this Annual Report, submitted our annual non-competing ADC progress report to NIA, begun to prepare for our five-year competing ADC grant application in September, and plan to hold a smaller conference for our young investigators when appropriate later this year. While it was necessary to cancel this year’s Annual Conference, it was a painful decision. We are pleased to report that the University of Arizona has again agreed to host next year’s conference and that Dr. Zaven Khachaturian (the galvanizing force behind development of the infrastructure for AD research and a valued advisor to our consortium) has again agreed to provide the Leon Thal Memorial Lecture at that time. Finally, we will evaluate the possible need to reschedule our annual Public Conference, which normally takes place in October, if indeed circumstances warrant a restructuring or rescheduling of this important event. Like everyone else, I have been astounded by the myriad of ways in which you, our clinical and research colleagues, have worked together to prioritize the safety and well-being of our patients, research participants, and their families, including our particularly vulnerable older adults, as well as the ways you have been there for each other. I have been moved by your compassion, creativity, sacrifice and “in this together” spirit, and by the courage of our clinical colleagues on the front lines. You have responded to this crisis with uncommonly common heroism, you have embraced the opportunity do so, and you have found ways to further address our longstanding goals along the way. I am extremely grateful to my clinical and research colleagues, patients, research participants and families in the Arizona Alzheimer’s Consortium for all you do to make us proud. You have found ways to address the needs of our patients and research participants, while continuing to make major contributions to the study of Alzheimer’s disease (AD), related disorders and the aging brain, and you continue to give us a chance to achieve our ambitious goals. 3 My Consortium colleagues could not be more grateful to our Arizona Department of Health Service leaders, elected officials, and organizational leaders for their enthusiastic and steadfast support. You have shown extraordinary support in financially good times and bad, including during the current crisis. You have recognized the need to make a difference in the fight against AD, shared our sense of urgency, and given us the chance to do so right here in Arizona. While not contagious, AD and related dementias have been described by the World Health Organization and other policy leaders as the coming 21st century pandemic, a ticking time-bomb that is projected to affect well over 100 million families around the world within the next 20 years due to the growing number of people living to older ages. Together, we have a chance to help transform the understanding, treatment and prevention of AD, and we have a fighting chance to do so before 2025. No matter how disruptive or long-lasting, we will do our part to respond to the COVID-19 crisis, we will continue to play leadership roles in the effort to avert the coming AD pandemic, and we will do so right here in Arizona. With best wishes for everyone’s health, safety and well-being during this challenging time, Eric M. Reiman, M.D. Director, Arizona Alzheimer’s Consortium 4 Introduction to the Annual Report Background The Arizona Alzheimer’s Consortium is the nation’s leading model of statewide collaboration in Alzheimer’s disease (AD) research. It includes more than 150 researchers and staff from seven principal organizations, including Arizona State University, Banner Alzheimer’s Institute, Banner Sun Health Research Institute, Barrow Neurological Institute, Mayo Clinic Arizona, the Translational Genomics Research Institute, and the University of Arizona, and from four affiliated organizations, including the Critical Path Institute, Midwestern University, Northern Arizona University and the University of Arizona College of Medicine, Phoenix. Established in 1998, the Consortium is intended to make a transformational difference in the scientific fight against AD, to engage Arizona’s underserved and understudied Native American and Latino communities, to help address the unmet needs of patients and family caregivers, and to advance the understanding and promotion of healthy cognitive aging. The Consortium’s major themes are the early detection and prevention of AD. Its primary goal is to find effective AD prevention therapies as soon as possible. The Consortium is widely recognized as a model of multi-institutional collaboration in biomedical research. It capitalizes on complementary resources and expertise from different disciplines and organizations to address scientific problems in the most impactful way. Its researchers receive critical support from the state of Arizona (through the Arizona Department of Health Services [ADHS]), the participating organizations, a competitive Arizona AD Core Center (ADCC) grant from the National Institute on Aging (NIA), and numerous other grants and contracts. Eric M. Reiman, MD, is the Director of the Consortium and the NIA-sponsored ADCC, Richard Caselli, MD, is the ADCC’s Associate Director, and Carol Barnes, PhD, chairs the Consortium’s 26-member Internal Scientific Advisory Committee. Mr. David Jerman is Administrative Director of the Consortium’s state- and organizational-supported research program, Mrs. Andrea Schmitt is Administrative Director of its ADCC grant, and Executives from each of the seven principal organizations serve on the Consortium’s Board of Directors. The Consortium’s external advisors include Drs. Marilyn Albert, Zaven Khachaturian, Bruce Miller, and Thomas Montine, who are internationally recognized for their contributions and leadership roles in the study of AD and/or related disorders. They conduct annual site visits, review the progress and productivity of the Consortium and ADCC, and provide formal feedback and recommendations to the researchers, NIA, and state. The Arizona Alzheimer’s Consortium capitalizes on the state’s strengths in brain imaging and emerging fluid biomarkers, genomics, the computational, mathematical and statistical analysis of complex data sets, the basic, cognitive and behavioral neurosciences, clinical and experimental therapeutics,