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(ARML) Program and Cognitive Aging and Memory (CAM) Program 2016 Annual Report

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(ARML) Program and Cognitive Aging and Memory (CAM) Program 2016 Annual Report Age-related Memory Loss (ARML) Program and Cognitive Aging and Memory (CAM) Program 2016 Annual Report Prepared for the McKnight Brain Research Foundation by the University of Florida McKnight Brain Institute and Institute on Aging Table of Contents Letters from UF/MBI Leadership .................................................................................................................................................................................. 3-7 Age-related Memory Loss (ARML) Program and the Evelyn F. McKnight Chair for Brain Research in Memory Loss...... 8-25 Cognitive Aging and Memory Clinical Translational Research Program (CAM-CTRP) and the Evelyn F. McKnight Chair for Clinical Translational Research in Cognitive Aging ....................................................... 26-59 William G. Luttge Lectureship in Neuroscience ...............................................................................................................60-61 Faculty Biographical Sketches ........................................................................................................................................ 62-184 Selected Publications .................................................................................................................................................... 185-315 Offi ce of UF Senior Vice President for Health Aff airs 1515 SW Archer Road, Suite 23C1 Gainesville, FL 32608 P.O. Box 100014 Gainesville, FL 32610-0014 Phone: 352.733.1700 Fax: 352.733.1201 UFHealth.org Patient Care ● Research ● Education UF Health is a collaboration of the University of Florida Health Science Center, Shands hospitals and other health care entities.s. 3 PO Box 100015 Gainesville, FL 32610-0015 352-273-8500 Office 352-846-0185 Fax mbi.ufl.edu January 15, 2017 The McKnight Brain Research Foundation SunTrust Bank Mail Code FL-ORL-2160 300 South Orange Avenue, Suite 1600 Orlando, FL 32801 Dear MBRF Trustees, It is my pleasure to submit this 2016 Annual Report of the Age-Related Memory Loss (ARML) program and the Cognitive Aging and Memory Clinical Translational Research Program (CAM- CTRP). In serving as the Interim Director of the Evelyn F. & William L. McKnight Brain Institute (MBI) of the University of Florida (UF) for most of this year, I sought to maintain the missions of the MBI and the associated facilities, and facilitate collaborations among researchers that would translate into therapeutic advances. I would like to express my sincere appreciation to the MBRF for your unfailing support of our programs and me during this transition period. 2016 featured significant changes in the MBI’s leadership and administration. Dr. Todd Golde became the MBI’s new Director on December 1, 2016, succeeding Dr. Tetsuo Ashizawa. My service as Interim Director ended commensurate with this appointment; however, I am pleased to continue serving as the MBI’s Deputy Director under Dr. Golde. Dr. Golde is professor of neuroscience and director of UF’s Center for Translational Research in Neurodegenerative Disease and the 1Florida Alzheimer’s Disease Research Center consortium of institutions. He has served the MBI for six years as both an investigator and a leader, pioneering programs to closely link basic-science laboratory work with patient-based studies to translate new discoveries into diagnoses and treatments. In accepting his new appointment, Dr. Golde stated, “We’ve made a lot of investments in neuromedicine and neuroscience research at the Health Science Center over the last five years,” he said. “We have outstanding investigators, and I want to help them collaborate, find synergies, and share resources so we can continue our growth in this area. Moving forward, we’d like more connections between research at the lab bench and care at the bedside.” In September, the MBI also welcomed a new Director of Operations, Mr. Kenneth Marx. Ken served previously as chief administrator for UF’s department of emergency medicine for 15 years and has over 25 years of administrative experience in academic medical centers. His knowledge of the College of Medicine and the UF Health Systems and personnel is of great value to the MBI and enables us to move forward rapidly. Ken succeeds Kelly Sharp, who is The Foundation for the Gator Nation An Equal Opportunity Institution 4 now executive director of administration and finance at the UF College of Pharmacy. We wish to thank Kelly for his numerous contributions to the MBI’s growth and success and for all he has done to help Ken and me this past year. He did much to enable the successes the MBI has had over the past 5 years. Other notable changes in 2016 include the reorganization of the CAM-CTRP group, directed by Dr. Ronald Cohen. Further description of these changes is provided by Dr. Cohen in his introductory letter to the CAM-CTRP section of this Report. We thank the MBRF for support in ensuring this transition was completed with minimal interruption to Dr. Cohen’s group’s research. CAM’s work, along with that of many other researchers at the MBI, will be augmented by the recent installation of a second 3T MRI magnet. The Siemens 3T MRI/S Prisma is a state-of-the- art $3 million scanner that has the strongest gradients available for human imaging, advanced motion correction capabilities and increased scanning flexibility. The addition of this unit and construction of the associated facilities were key features of a broader renovation of the MBI’s Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) core facility this past year. Much excellent work has been performed this year by the members of CAM-CTRP and the ARML programs. As brief examples, the ARML members have received 5 new NIH grants— three to Dr. Burke, one to Dr. Maurer, and one to Dr. Foster. These are focused on mechanisms of aging and are the beginning of the translational pipeline to the CAM. The CAM faculty had several papers in high profile journals, addressing age-related impairment in executive function examined at the circuit and molecular levels, as well as studies addressing pharmacological treatment involving GABAb receptors. The ARML continued to make progress in facilitating collaborations across institutes, including establishing protocols for examining exosomal microRNA as part of the Cognition and Neuroimaging Core and development of a computational pipeline for analysis of genome-wide methylation data (DMAP2) for examining the epigenetics of age-related memory impairment http://compbio.ufl.edu/software/dmap2/. ARML faculty and students also established collaborations addressing the unique and emerging idea that cognitive decline involves an interaction of the brain and peripheral systems. Peripheral factors such as systemic inflammation, exosomes in the blood, and age-related changes in peripheral organs (e.g. muscle) can result in sleep disturbances and a decline in executive function and memory, which are observed in the elderly. The exciting aspect of these investigations is that they appear approachable by therapeutic interventions. The CAM-CTRP group also had an extraordinarily successful year. A number of large grants were funded, one of which was the ACT R01, a multisite randomized control trial funded by the NIA for combating cognitive aging using noninvasive adjunctive interventions. This will be the largest tDCS trial in history, and the first multisite clinical trial across multiple McKnight sites. CAM also was key in the establishment of an MBRF-supported Cognitive Aging and Memory Intervention Core across all McKnight Brain Institutes. This Core will facilitate multi-MBI site clinical trials and collect information on MBI-based clinical trial resources and investigators 5 (PIs: UA, Gene Alexander, UAB: Virginia Grissom, UM: Tatiana Rundek, UF: Ron Cohen and Adam Woods (contact PI). While we regularly announce publications and grant submissions, one particular CAM manuscript providing evidence that short and long-term heavy drinking behavior accelerates cognitive aging (published in Alcoholism: Clinical and Experimental Research) was covered by over 50 online and other media outlets, including US News and World Report. Finally, Dr. Cohen received funding for the SHARC study, a U01 from NIAAA that was a renewal funding for the Southeastern HIV and Alcohol Research Center. This renewal funding was obtained with Dr. Cohen as deputy director of SHARC, with specific focus on how HIV and alcohol accelerate cognitive aging, a prime model of a co-morbid condition’s impact on the aging process in the human brain. Thus, while we continue our mechanistic basic science research and descriptive clinical studies, we are delivering on a challenge to strengthen the collaborations between CAM-CTRP and ARML programs, with the aid of new translational members of the teams. We hope to further develop our clinically meaningful translational research, which we anticipate will flow from bench to bedside, and with the help of our clinical translational colleagues, back to the bench for proof of mechanism when a relevant clinical observation is made and needs further basic studies to confirm and develop potential interventions. As discussed frequently by the Board and the leadership of CAM-CTRP and ARML, we need a number of researchers who will work closely with both basic scientists and clinical scientists to operationalize this pipeline. It is my privilege to be one of those scientists. Dr. Golde’s vision includes facilitating this pipeline in aging and memory research; he and I will both be part of the clinical
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