Appendix I: McKnight Brain Institute Strategic Plan

• Dr. Rundek is a collaborative clinical researcher with established extensive collaborations on these large NIH-funded studies at Columbia University (INVEST and U01 eMERGE), at

Albert Einstein in the Bronx (Einstein Aging Study), and with national and international consortia (NINDS SiGN, ISGC, MRI-GENE).

• Drs. Sacco and Rundek have an active genetic research program as a part of the Family

Study with Dr. Blanton and Dr. Liyong Wang from the Miami Hussman Institute for Human

Genomics (HIHG).

• Drs. Sacco and Rundek participate and collaborate with the Hispanic Community Health

Study- Study of Latinos (HCHS/SOL), which is a multi-site NIH contract.

• Dr. Rundek collaborates with Mt. Sinai at Miami Beach, Florida International University (FIU) and Florida Atlantic University (FAU) on the Brain Vascular Imaging Phenotypes (VIP) study.

• Dr. Rundek collaborates with UM CFAR (Center for AIDS Research). As a result of this collaboration, the HIV Aging Scientific Working Group (HIV SWG) was recently established under co-leadership of Dr. Rundek.

• Dr. Della-Morte and Dr. Rundek are collaborating on a project aimed to evaluate the association between a well-established biomarker of systemic inflammation, the

Arachidonic Acid/Eicosapentaenoic Acid (AA/EPA) ratio with biomarkers of carotid atherosclerosis and biomarkers of cognitive degeneration. A NIH R21 grant proposal is projected to be resubmitted after addressing the reviewers’ comments.

• Dr. Della-Morte and Eng. Eugenio Martinelli launched as Co-Directors the IC-LOC (Interdisciplinary center for advanced studies on Lab-on-Chip and organ on-chip applications) Institute of Research at University of Tor Vergata, Rome.

Briefly Describe Plans for 2021

1. The MBI Strategic Plan

Our plan is to move forward with the implementation of the MBI Strategic Plan in 2021. In the First phase of the implementation, we will present our MBI Strategic plan to all of our MBI constituency and familiarize them with our MBI mission/vision and strategic plans. We will work with our members and collaborators to adopt our Core values and clearly present our Guiding principles, Goals and Strategies, Competitive Advantages, Plans, Actions, Metrics and Deliverables. Multiple meetings with various constituency will be organized to present and adopt our MBI Strategic Plan. It is imperative that in this first phase we clearly communicate: - What we do the best, - Who we are and why we exist, - What we stand for, - Where we are going and why, - What the strategic topics and issues are we need to address; and - What plans we need to align with.

It is likely that this first phase will take a significant amount of time in order to present our goals and objectives clearly and understandably, and most importantly, to articulate a crystal clear strategic direction of our MBI for the next 5 years.

The Second Phase will be planned in the later part of 2021 in order to clearly define who will be involved in specific goals, what their actions and deliverables will be, to provide tools and support, and estimate timelines for the completion of actions and goals.

Our MBI leadership will steer the MBI Strategic Plan implementation and manage its performance. The Scientific Advisory Board will oversee the MBI Strategic Plan implementation process and provide additional input if our Strategic Plan needs revisions during the process of implementation and execution.

The brief plans for 2021 presented below are listed by categories and selected individual MBI members and collaborators in alphabetical order:

2. Clinical-Translational and Population Based Research

• Dr. Crocco will develop a registry of well-characterized African American older adults at risk for Alzheimer’s disease and related dementias for the project “Building an Advanced

Cognitive and Biomarker Registry for African American Older Adults At-Risk for Alzheimer’s

Disease.” The project aims to assist in closing the gap of health disparities for these vulnerable older adults through clinical evaluation, novel cognitive tests sensitive to early cognitive impairment, as well as blood biomarkers and neuroimaging.

• In addition to the work Dr. Galvin will perform on his currently funded studies he will work on these projects in 2021:

- “Natives Engaged in Alzheimer’s Research (NEAR)” aims to engage, enroll and study American Indians, Alaskan Natives, and Native Hawaiians and Pacific Islanders in novel Alzheimer detection and treatment interventions and encourage biomarker and autopsy program participation. This project is submitted to NIA with Buchwald, Galvin, Kauwe (MPI) with Priority Score: 17 (No Percentile on P01 grants). “A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Study to Evaluate the Safety and Efficacy of CT1812 in Subjects with Dementia with Lewy Bodies” was submitted to the /NIA. The major goal of this project is to conduct a Phase 2 clinical trial of CT1812, a novel disease-modifying compound, in patients with mild to moderate dementia with Lewy bodies (DLB). Caggiano, Galvin (MPI) Role: MPI. Priority Score: 31 (16th Percentile). “Multicultural Community Dementia” Screening will conduct a population-based dementia screening, validate findings in a longitudinal study of ADRD biomarkers, and establish the potential benefits and harms of dementia screening in a multicultural sample. This proposal is submitted to the NIA, Role: PI. Priority Score: 34 (14th Percentile). - “Wabanaki Native American Research Centers for Health (NARCH)” was submitted to the NIGMS. The major goals of this project are to create research infrastructure to enable the Wabanaki Confederation to develop sustainable clinical and translational research programs in brain aging and dementia. Role: Project 1 Co-Lead. Priority Score: 26 (No Percentile on S06 grants). • Dr. Gomes-Osman will work on two proposals:

- ‘K01 Career Development Award,’ which was submitted to NIH in February 2020, scored but not funded. She resubmitted this grant in November 2020 and the reviews are pending.

- She submitted a grant proposal to the McKnight Research Foundation (MBRF)

Cognitive Aging and Memory Intervention Core to research: Harnessing Optimal

Mechanisms of Exercise for Cognitive Gains (HOME-Cog). It is a collaborative project between the Evelyn F. McKnight Brain Institutes (MBI) at University of Miami and

University of Florida that aims to inform the knowledge gap on the mechanistic action of exercise on the brain by characterizing important mechanisms of neuroplasticity and cardiovascular capacity, proposed to underlie cognitive response to exercise. The awardees haven’t been announced yet.

• Drs. Jiang and Wang will study the effect of circuit resistance training on retinal vascular and neuronal functions in older people. They plan to submit an R01 application to the NIH in 2021.

• Dr. Levin will work on these projects:

- “Vestibular Outcomes in Adults with Cognitive Impairment,” which was submitted to

NIH in collaboration with Dr. Liu from ENT. This study examines the interactions and overlap between vestibular, auditory and cognitive networks and their shared relationship throughout the aging process. If funded, it will begin in 2021.

- Dr. Levin will be working on the study recently funded by the Ed and Ethel Moore

Alzheimer Disease Research Program (DOH). The plan is to develop an educational intervention for Hispanic and non-Hispanic elderly individuals and their caregivers/partners who are residing independently in the community but susceptible to being scammed.

- Dr. Levin and her team will delve into data analysis for the psychosocial and neuropsychological components of the McKnight Brain Aging Study (MBAR). Dr.

Rundek will lead the development of manuscript proposals from MBAR results.

• Dr. Ramos started a new project with Avadel Pharmaceutical in 2020 titled “Open label study evaluating the effect of single dose sodium oxybate in Narcolepsy.” Work has started with planning the logistics, budget and IRB, but study recruitment will take place in 2021.

• Dr. Rundek will be working on a number of projects in the next year, including:

- “Carotid Ultrasound Imaging Markers of AGINg and Endothelial function in Risk of

Alzheimer’s Disease: The Florida IMAGINE Study of AD Risk,” which is new FL DOH Ed and Ethel Moore Alzheimer Disease Research funded research project.

- Dr. Rundek will continue her work on the “Family study and genetic and epigenetic risk of cognitive impairment,” funded by the NIH.

- She will continue her work as on the “Brain Vascular Imaging Phenotypes and Vascular

Comorbidities in Risk of Alzheimer Disease” that is funded by the NIH.

- Training and education in Clinical translational research as a part of “OneFLorida ADRC

REC AlzSTARS” program funded by NIA and working in the Clinical Core of 1FL ADRC on dementia adjudication.

- “COVID-19, Social Distancing, and Cognitive Impairment in 1Florida ADRC participants,” which is a new supplement awarded to 1FL ADRC. Dr. Rundek is MPI together with Dr. Curiel (UM) and Dr. Smith (UF).

- “Einstein Aging Study” competitive renewal will be submitted in 2021 and Dr. Rundek will be a MPI on a project on vascular contribution to the sleep and cognition in aging together with Dr. Carol Derby from Albert Einstein in NY.

- “HIV and Aging Scientific Working Group (SWG)” collaboration is a new group established by the UM CFAR (Center for AIDS Research) under co-leadership of Dr. Rundek. A UM CFAR competitive renewal will be submitted in 2021 and HIV SWG will be a separate proposal that Dr. Rundek will work on closely with the CFAR leadership.

• Dr. Sacco will continue his multiple and large research projects and leadership programs.

A planning phase for a renewal of the UM CTSI that he leads will start in 2021. He will also work on a resubmission of the NINDS NOMAS project in 2021 with the important goal to determine the role of specific immune and innate immunity pathways as well as gut microbiota-derived metabolites in longitudinal cognitive impairment. This program will provide data needed for a discovery of novel targets in the immune and specific metabolite pathways to prevent cognitive decline.

• Dr. Seixas-Saporta is currently working on the analysis of the McKnight Frailty Project data and plans to publish the results in 2021.

3. Basic Science

• Dr. Della-Morte will work on two projects:

“The Batman Project” that aims to investigate the mechanisms of defense against virus typical of bats that can be translated to fight against COVID-19 Pandemic. This project is funded by the University of Tor Vergata.

- “The role of PUFAs in Subclinical Cerebro-vascular Imaging Phenotypes and Clinical

Vascular Disease” This project was submitted as R21 to NIH with plans for resubmission this year.

- “PERSEO - Biological utilization of Organ on a Chip Technology” this project was submitted to the Italian Minister of Health and work will start in 2021 if funded.

• Dr. Raval will be working on the research project "Therapeutic interventions for poststroke rehabilitation." She will aim to get a better understanding of how nicotine in combination with oral contraceptive leads to altered energy metabolism. This will help her to design novel therapeutic targets to lower cerebral ischemic damage in co-morbid ischemic patient populations which is the goal of this upcoming research.

• Dr. Vontell will be working next year on one of the proteins thought to be involved is Neurogranin (Ng), which is a protein kinase C substrate that binds calmodulin in the nonphosphorylated state in the presence of low Ca2+ concentrations. Ng is thought to play

a role in the cascade of events for the postsynaptic transmission and it is triggered by the binding of glutamate to NMDA receptors, particularly in the hippocampal region. Therefore, it plays an important role in learning and memory and CSF Ng is considered a biomarker for synaptic dysfunction. She will explore the mechanism underlying selective synaptic damage and memory loss seen in aging and AD.

4. Education

We see the need now more than ever to develop a robust scientific educational program. With faculty and staff working in separate locations, education is a great way to keep all informed and connected, albeit virtually. Our MBI 2020 Research Seminars Series via Zoom was better attended than ever, with attendance by faculty, clinicians, trainees and researchers from various Centers, Institutes and affiliations. We were able to learn more about other UM aging programs and disciplines, to have great scientific discussions, to hear fresh ideas and truly utilize every moment of meeting time to collaborate and plan future MBI collaborations. We are planning more interactive brainstorming/collaborating research meetings and new research seminars in our series in 2021.

Providing outreach and education to the senior community on aging and healthy brain initiatives is part of our strategic plan and it is especially essential to reach this population now. We will continue to partner with the Miami-Dade Public Library System and other community resources. The Miami-Dade Mayor’s office changed leadership this fall but we hope to connect with the new mayor in 2021 about continuing the Mayor’s Initiative on Aging program. We will be partnering with the city of Doral’s Silver Club which encompasses 900 members, of which 200 are currently very active to provide education and outreach. The Connection with the Doral Silver Club has already been made through the Councilwoman Digna Cabral in the City of Doral. We are planning an array of virtual educational offerings and activities both in English and Spanish.

5. 12th Annual McKnight Brain Research Foundation Inter-Institutional

Meeting

The agenda has been finalized and logistical details and further plans will be finalized in 2021. The draft agenda is attached in Appendix VIII.

Were any funds used for a Prohibited Purpose during the report period?

N/A

Endowment Investment Results and Budget

See Appendix VI.

Do you recommend any modification to the Purpose or mandates in the Gift Agreement?

No

Did all activities during the report period further the Purpose?

Yes- Completion of our Strategic plan will considerably further our MBI purpose.

Please describe any negative events (loss of personnel, space, budget, etc.) that occurred during the report period and the possible impact on carrying out the Gift Agreement.

The Pandemic and resulting lockdown affected some MBI plans for 2020 including many research studies being on hold and canceling the McKnight Brain Research Foundation 12th Annual InterInstitutional Meeting. The 12th Annual Inter-Institutional Meeting will be held virtually on April 28-29, 2021.

Please provide any general comments or thoughts not covered elsewhere – a response is not required. Please respond only if you would like to add something not otherwise covered elsewhere.

N/A

What social media platforms are you active on and how many followers do you have?

Our MBI is active on the social media channels using the University Miller School of Medicine @Umiamimedicine and the Department of Neurology @Umiamineuro channels with hashtags #UMMBI. The channels have developed substantial followers over the past 5+ years, thus offering a much broader platform than just the one the UM-MBI could develop and create. We have a presence on Facebook, Twitter and Instagram. Facebook has 6,300 followers with an average of 150 reached by UM-MBI related posts. Twitter has 800 followers with an average of 100 reached by UM-MBI related posts. Finally, while our Instagram channel has 1,599 followers, we have not used it for MBI posts. We utilized social media to recruit for the Precision Aging Pilot Project. These are explained in Appendix VII.