EMBI Annual Report 2022

A P P E N D I C E S

APPENDIX 1 ...56

List of McKnight Affiliate Faculty and Trainees

APPENDIX 2 ...63

Top 20 Publications from FY22

APPENDIX 3 ...67

Presentations at scientific or public meetings

APPENDIX 4 ...73

Highlights of website development, media coverage and/or social media audience development

APPENDIX 5 ...87

Update on McKnight Neurocognitive Scholar Christian Agudelo, MD

Dear Trustees:

Please find enclosed the University of Miami Evelyn F McKnight Brain Institute Annual report As I reflect on 2022, I am proud of many things that demonstrate the maturing and expansion of our EMBI. If you visit our website at https://mbi-umiami.org and our social media pages, you will understand that our EMBI umbrella has grown in its coverage of cognitive clinical and translational research in all divisions in the Department of Neurology and the brain health and cognitive programs at the University of Miami Miller School of Medicine.

In 2022, the Department of Neurology at the University of Miami was ranked #25 in the US News and World Report in the Neurology and Neurosurgery specialty and, even more impressive, #18 in NIH funding Our EMBI continues to develop scientific programs according to our strategic plan and continues to offer a broad range of clinical and research training opportunities to clinical and translational trainees and researchers Led by Dr Rundek as the scientific director and the Evelyn F McKnight Chair for Learning and Memory in Aging, our EMBI focuses and offers a wealth of knowledge in clinical translational research, education, and mentorship, and provides neurocognitive research opportunities, all that are detailed in the report I am happy to confirm that Dr James Galvin, who is a world-renowned cognitive neurologist and researcher has started as the Chief of the Cognitive Division and has expanded the Comprehensive Center for Brain Health’s (CCBH) research and outreach into the in Boca Raton/Palm Beach community Our EMBI works closely with CCBH on clinical research and research mentoring, and clinical education and training in cognitive aging and brain health.

We continue our successful work on the integrative and collaborative programs with the Center for Neurocognitive Sciences and Aging led by Dr. David Loewenstein in the Department of Psychiatry. We have also extended our collaborations across the University, particularly through our Clinical Translational Science Institute (CTSI) and institutional neuroscience and aging collaborative programs and initiatives under leadership of Drs. Rundek, Loewenstein and Galvin in collaboration with the Department of Neurosurgery, Miami Project to Cure Paralysis, Center for AIDS Research (CFAR) and others Our collaboration with other EMBIs is strong We supported our Inter-institutional meeting this year and traveled to Arizona to attend the meetings in-person We work collaboratively on large projects with UA and on other grants and pilots with UF and UAB Our collaborations with other national institutions and partners is also strong We continue our research collaborations and programs with Columbia University, Albert Einstein in New York, University of Chicago, USCD, Harvard, and established new partnerships such as with University of Louisville We are partners with the AHA, AAN, and other professional and scientific organizations and NIH networks, including NeuroNEXT, StrokeNet, and ADRC.

L E T T E R F R O M T H E E X E C U T I V E D I R E C T O R

Dr. Rundek continues her work as the main PI for research training and education for the 1FL ADRC. She co-directs the 1FL ADRC AlzSTARS (Alzheimer's Disease Science Training to Advance Research Success) program together with Dr Glenn Smith at UF As Director of NIH StrokeNet and NeuroNEXT Training programs as well as of CTSI Kl2 program and MS in Clinical Translational Investigations, Dr Rundek is a key mentor to trainees in these programs Our mentees obtained K and K-like grants We expect more success as Dr Rundek has just received funding for a T32 in collaboration with Dr Jean-Louis in the Department of Psychiatry and submitted two additional T32s and a R25 with aging and neuroscience focus

Our strategic plan is entering the third year We are ahead in accomplishing our strategic goals in research, education, collaborations and community outreach. We are dedicated to our DIRECT (Diversity, Integrity, Responsibility, Excellence, Creativity, Teamwork) values. Our EMBI team is strong, cohesive, effective, and collaborative and is a role model for any collaborative research team.

Challenges however remain, while Covid has allowed us to reach many patients and research participants without Miami travel issues, the in-person portion of some studies continues to be limited. Together with Dr. Baumel and now with Dr. Galvin, our clinical and educational activities will continue to grow with the opportunities to recruit at least two more cognitive neurologists and train a strong team of clinical cognitive neurologists-scientists Our current neurocognitive team has provided virtual care for more than 2,000 patients this year

In 2023, we will continue our leadership in research, training and mentorship of the next generation of successful cognitive physician-scientists by recruiting another Evelyn F McKnight Neurocognitive Clinical Scholar in Brain Health and Aging as part of our postdoctoral training program With Drs Rundek, Sun, Levin, and Galvin, along with all existing EMBI faculty and EMBI Scientific Advisory Board members, the University of Miami EMBI and the Department of Neurology will continue its unique cognitive aging and memory clinical translational program and continue to advance research in age-related memory loss and cognitive decline and brain health through new programs, grants and other multi-disciplinary collaborations and partnerships. Finally, in January of 2023 the Alexandria and Bernard Schoninger Chair in Memory Disorders will be awarded to Dr. Galvin.

As I battle my health issues, I feel confident that our EMBI is in the capable hands of our team under leadership of Dr. Rundek, who has my full support as well as the support of our Institution, Dean Ford, our Scientific Advisory Board, and the leaders of the other EMBIs

Thank you for your continued support and collaboration in our efforts

Warmest regards, Ralph L. Sacco MD, MS, FAHA,

Dear Trustees:

As I reflect on 2022, I am proud of my 5th year co-leadership of the EMBI at the University of Miami Department of Neurology. Our EMBI continues achieving the objectives in all areas of our strategic plan goals: research, education, collaborations, and community outreach. We innovate and continue to extend our collaborations within our Institution, with other EMBIs, and with institutions nationwide. Our EMBI team is effective, collaborative, productive, and continuously strives to improve and advance our mission. We openly communicate and share our EMBI activities and results at multiple forums, from our weekly administrative and research meetings, to monthly seminars and journal clubs, clinical and research training programs and community outreach through social media and educational events. As a matured organization our formal Scientific Advisory Board meets formally twice a year, but also convenes at Dean’s team science research meetings, and Clinical Translational Science Institute collaborative neuroscience activities

We have advanced almost all our four strategic goals for 2022: (1) Continue development of our scientific programs directly related to our EMBI and the McKnight Brain Research Foundation mission Our new NIH grants and the Comprehensive Center for Brain Health (CCBH) led by Dr James Galvin continues the expansion of our research and scientific programs; (2) Continue clinical translational education and mentorship Dr Christian Agudelo, Michael Kleiman and Anita Saporta are advancing this goal together with Taylor Ariko, our PhD student in medical bioengineering, who will advance machine learning algorithms for the assessment of neuroimaging and cognitive phenotypes; (3) Promotecommunicationsand collaborations. We have significantly advanced our EMBI branding, established our EMBI logo and participated in several collaborative inter-institutional projects; and (4) Develop community outreach. We have been on the frontiers of social media outreach in our community and the leaders in virtual social and education events. We plan to continue with this major focus in 2023. I am also extremely proud of our exemplary EMBI research administrative team, Susan Fox-Rosellini, Stacy Merritt, and Marti Flothmann, who continue improving our web, social media development, and our community outreach.

In November 2022, I was elected to the Academy of Science, Engineering and Medicine in Florida (ASEMFL), a great honor which will expand my collaborations across the State of Florida and facilitate my engagement in discussions about research and global challenges our society faces I continue as President of the Intersocietal Accreditation Commission (IAC) Vascular Testing Board of Directors, the largest national accreditation body that accredits clinical nuclear/PET, MRI, CT, ultrasound, cardiac echo, and carotid stenting programs We have increased the number of accredited vascular testing facilities, particularly in neurovascular testing services, and through accreditation and research improved care for patients with vascular cognitive impairment (VCI).

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T T E R F R O M T H E S C I E N T I F I C D I R E C T O R

We have published a seminal IAC paper on the revised criteria for carotid stenosis that are now being adopted by many institutions as a new standard of care in their clinical practice for patients with carotid atherosclerotic disease, stroke and VCI.

This year was again full of achievements, but also challenges. In the first part of a post-Covid 2022 environment, we continued to be concerned for the health of our team members, patients and study participants Despite these issues, our programs have successfully continued and thrived, and our team members were encouraging and supportive of all of our EMBI members, collaborators, study participants, trainees and the community we serve

In our report and in this letter, we highlight our achievements, from numerous training and research grants submitted and received, to educational and training activities, success of our EMBI scholar and other trainees, community outreach and numerous established collaborations and new initiatives within our institution, with other EMBIs, and across institutions nationwide Among our most notable, is a renewal application of our CTSI in September, where I led the submission of CTSI K12 program as a Director. I have submitted six training grants to NIH as MPI (three T32s, one R25, NeuroNEXT and FL DOH fellowship); one T32 and FL DOH just received funding, one would need to be resubmitted and others are pending reviews. I have also submitted several collaborative NIH grants, which are pending review. It has been an intensive grant writing period and it will continue in 2023!

In 2023, I am committed to continue guiding the execution of our strategic plan, advancing our scientific and education mission, and advancing our training and mentorship In addition, I will continue advancing the Research Educational Core for the 1FL ADRC AlzSTARS (Alzheimer's Disease Science Training to Advance Research Success) program, which now has 8 trainees; 2 of which are from our EMBI, Magda Tolea and Regina Vontell In our collaborative and successful NIA award Precision Aging Network (PAN) led by Dr Barnes, I have taken a co-lead role of the PAN2 clinical project with Dr Lee Ryan We had a successful PAN startup year We prepared all regulatory and study documents, obtained IRB approval, prepared SOPs, and trained research teams in all procedures and data collections for a complex 2-day study visit protocol As a lead of the PAN2 Neurosonology Core in Miami, we completed in-person training sessions of all PAN sonographers from Emory, Johns Hopkins and U Arizona, in Miami, and certified them for performance of the standardized ultrasound scanning protocols.

To further advance our strategic programmatic development, I will continue to develop collaborations with other Centers and Institutes at UM as well as other EMBIs. This includes strong collaborations with the Cognitive Division and Comprehensive Center for Brain Health led by Dr. Galvin, who was appointed the new Director of our Cognitive Division this year. Our collaborations will continue with Center for Neurocognitive Sciences and Aging (Dr. Loewenstein), Hussman Institute for Human Genomics (Drs Pericak-Vance and Blanton), and Clinical Translational Science

Institute (CTSI) and Neuroscience program I will continue to be a senior leader of CFAR Scientific Working Group on Aging in HIV and serve on the CFAR Steering Committee I will also closely work with our Education Director Dr Sun on advancing our education mission and recruiting the best candidates for the Evelyn F McKnight Neurocognitive Clinical Scholar in Brain Health and Aging in 2023/2024

Finally, our EMBI is delving into several new and exciting research areas including, Neighborhood Greenness and Cognitive Performance, that was recently funded by NINDS and for which I serve as a MPI, Sleep in Neurocognitive Aging and Alzheimer’s Research (SANAR) led by Dr. Alberto Ramos that was just funded, a new study on cardiac determinants of cognitive health recently submitted to NIH in collaboration with Columbia University, four new federal grant research projects awarded to Dr. Galvin, and other grants, projects and research activities.

I am looking forward to another exciting and productive year for our EMBI.

Warmest regards, Tatjana Rundek, M D , Ph D

SCIENTIFIC DIRECTOR

Dear Trustees:

It has been a great pleasure to serve as the Education Director of the Evelyn F McKnight Brain Institute (EMBI). On behalf of the EMBI Education Program at the University of Miami Miller School of Medicine, I am pleased to present a summary of the educational activities organized at our institute in 2022.

Under the leadership of Dr. Sacco and Dr. Rundek, our EMBI educational program continued to play a vital role in providing education for the entire EMBI, in cultivating young scientists, physicians and students for their career development and research in aging and cognitive neurology as their career choice. We focused our efforts on reaching the diverse communities of South Florida to provide education on brain wellness in the aging population

General EMBI Education

We are committed to creating a nurturing learning environment for our neurology staff, graduate students, residents, fellows, and faculty at EMBI We organized a diverse range of research seminars, journal clubs, and brain cutting sessions for EMBI members, collaborators and trainees

Our educational activities were well attended and highly evaluated for relevance, impact and innovation We arranged presentations for our trainees giving them opportunities to hear feedback on their research projects and to improve their research and presentations skills as well as academic achievement outcome. We have supported our faculty and trainees by providing targeted research training in their specific interests and disciplines. We encouraged faculty and trainees to enroll in various workshops such as those offered through the CTSI (Clinical Translational Science Institute), including the research mentoring training program and grant writing workshops.

EMBI Training Program

One of our important missions in our EMBI is to support career development in cognitive neuroscience for the next generation. To provide individual training opportunities, we have focused on obtaining grants poised to recruit additional post-doctoral trainees as well as to fund current trainees and junior faculty Dr Rundek applied for and was awarded 2 training grants (T32 and FL DOH fellowship), which will facilitate the growth of our training program goal to increase the number of scientists and clinicians trained in aging and cognition Our EMBI faculty serve as educators and mentors for trainees with impressive grant portfolios including, an R25, K24, T32, Florida DOH, NIH and 1 Florida ADRC Center grants EMBI trainees are actively applying for F, K and R awards as well as other K-like foundation awards (e g American Heart Association, American Academy of Neurology, National Science Foundation and others)

L E T T E R F R O M T H E E D U C A T I O N D I R E C T O R

EMBI Community Outreach Program

This year we strived to provide outreach and education with the goal of maintaining and improving brain health in the aging population. We reached both Hispanic and non-Hispanic community members in Monroe, Dade, Broward and Palm Beach Counties. We worked with our current aging organization partners and continued to make new partnerships. We organized our Lecture Series for the fourth year with the Miami-Dade Public Library System and received overwhelmingly positive feedback with many requests for more series like this.

In 2023, we will increase our scope of EMBI education programs in-house and in the community. We will continue to organize seminar series, journal clubs, and brain cutting sessions. We plan to organize targeted research seminars to facilitate grant application and collaboration across institutes. We plan to recruit excellent candidates to be trained in cognitive neurology and neuroscience. Our focus will continue on obtaining post-doctoral training grants to satisfy the need for clinicians and scientists who can effectively and efficiently translate science into practice in the field of normal brain aging and Alzheimer’s and Alzheimer’s related disorders (AD/ADRD) for our rapidly growing aging population.

In 2023, I am planning to take a more prominent role in our Endowed Brain Bank. I will extend our education and research activities to include more brain pathology and neuroscience education for our trainees in neurology and psychiatry. I will also work with Dr. Rundek on identifying an EMBI Associate Education Director, who will help extend our education activities and who will be mentored to be my successor as I transition to a position of Director of Brain Bank in the next several years.

Thank you for your continued support and collaboration in our education and training efforts.

Warmest Regards, Xiaoyan Sun, MD, PhD

I N T R O D U C T I O N

In concert with our MISSION to accelerate discoveries of the causes and treatments of age-related memory loss and cognitive decline, to promote brain health through multi-disciplinary collaborations and partnerships, and to train new generations of skilled clinical and translational scientists specializing in age-related memory loss, cognitive decline and the promotion of brain health, along with our VISION to become a leading center for clinical and translational research into the causes, treatments and prevention of age-related cognitive disorders and promotion of brain health, the University of Miami Evelyn F. McKnight Brain Institute has strived to blossom and expand our reach. In this year’s report, we describe how we propelled our mission and vision forward.

Our Evelyn F McKnight Brain Institute (EMBI) continued to flourish in this post-pandemic environment, and we are so excited to share our achievements Dr. Sacco was selected by the American Heart Association (AHA) as a distinguished scientist and Dr. Rundek was elected to the Academy of Science, Engineering and Medicine of Florida (ASCMF). Dr. Galvin was appointed Chief of the Cognitive Division and his precision aging-like personalized medicine model for brain health became actualized with the opening of the Comprehensive Center for Brain Health (CCBH) Dr. Ramos started his large, multi-centered R01 research on sleep and neurocognitive aging Dr. Camargo completed all data collection for his McKnight Brain Foundation and AAN awarded research project entitled Reducing the Effects of Aging on Cognition with Therapeutic Intervention of an Oral Nutrient: A Pilot Trial (REACTION). Our EMBI was well represented at the 2022 Alzheimer’s Association International Conference (AAIC) in San Diego, Ca. We actively participated in the 13th McKnight Annual Inter-Institutional meeting held at the University of Arizona in Tucson Furthermore, we published impactful papers in the field of brain and cognitive aging research Drs. Rundek and Levin successfully initiated the NIA U19 Precision Aging Network (PAN) research project at the University of Miami. Dr. Sun expanded our educational collaborative programming and enhanced our specialization of community outreach and partnering. We continued to mentor numerous trainees who are successfully obtaining NIH K and K-like awards. Dr. Rundek submitted four NIH training grants to continue to support training programs and reach the next generation of clinician-scientists in cognition and aging She also co-led the resubmission of the University of Miami Clinical Translational Science Institute to NCATS as Director of the K12 Mentored Research Career Development Program in Clinical and Translational Science. Our commitment to broadening our reach within the community we serve via website and social media continued to be successful.

Our EMBI scientific, programmatic, training, education and outreach achievements and our most important achievements are described in this section, Institute FY22 at a Glance.

S c i e n t i f i c A c h i e v e m e n t s

D r . S a c c o ’ s A H A H o n o r

Dr. Sacco was selected as one of the American Heart Association’s (AHA) distinguished scientists, joining the ranks of other eminent professionals. The American Heart Association's Distinguished Scientists are a prominent group of scientists and clinicians whose work has importantly advanced our understanding of cardiovascular diseases and stroke. This award was created over 10 years ago to recognize AHA members for significant, original and sustained scientific contributions that have advanced the association's mission "Building healthier lives, free of cardiovascular diseases and stroke." Recipients of this prestigious award are honored during the Presidential Session at AHA Scientific Sessions.

D r . R u n d e k ’ s A S E M F L H o n o r

Dr. Rundek has been elected to the Academy of Science, Engineering and Medicine in Florida (ASEMFL). The ASEMFL is to the state of Florida what the National Academies of Science, Engineering, and Medicine are to the nation. The Floridabased organization is focused on providing unbiased, expert advice to state government and other organizations on current and future challenges facing the world and Florida in particular. To this end, ASEMFL elects scientists, engineers and physicians from around the state who have achieved national and international recognition for their scientific accomplishments.

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Dr. Galvin and his recently recruited and talented research team at the Comprehensive Center for Brain Health (CCBH) work has focused on applying a precision medicine-like, personalized approach to brain health and the prevention of cognitive decline. He has successfully obtained four new NIH funded research projects this year. His team in total has 28 grants (NIH, Alzheimer's Association, American Academy of Neurology/McKnight, and others) currently totaling $155 Million. To accomplish the objective of these projects, Dr. Galvin and his team have established 56 unique research collaborations with academia, industry and community partners as illustrated in the model below that used Social Network Analysis. This model illustrates not only the density and complexity of their research collaborations, but also defines two distinct networks, one focusing on brain health and dementia prevention and Alzheimer’s Disease (AD), and another focusing on Lewy body dementia (LBD).

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’ s C o l l a b o r a t i v e S u c c e s s

We highlight one of Dr. Galvin’s major projects, a brain health platform that is shown to correctly segregate healthy controls from MCI and ADRD in a time and cost-efficient fashion. He developed a brain health platform that combines resilience, vulnerability and performance to assess brain health and the risk of Alzheimer’s disease and related disorders (AD/ADRD). He uses a combination of measures that take approximately 15 minutes to evaluate an individual and therefore use precision aging techniques for developing personalized strategies. He has a patent pending for his brain health platform. His overall objective involves researching the brain and cognitive aging and building a better brain through the aging process.

C O L L A B O R A T I O N S ( 5 6 )

R A I N H E A L T H / A D

E W Y B O D Y

E M E N T I A

S u c c e s s o f S A N A R

The success of Dr. Alberto Ramos’s Sleep in Neurocognitive Aging in Alzheimer’s Disease (SANAR) study was among our EMBI major scientific accomplishments this year. This $14 million R01 multicentered grant was awarded to investigate the impact of obstructive sleep apnea (OSA) on cognitive aging and the risk of Alzheimer’s disease and other related dementias in Hispanic/Latino adults. It is a grand study requiring an abundance of coordinating across the four major US sites, committees, staff and Co-PIs to operationalize. Dr. Ramos together with his co-investigators and Dr. Rundek has assembled a research analytic team composed of a senior statistician, two neuroscience graduate students, two neurology instructors and experts in cognitive disorders and neuroimaging markers of neurodegeneration. In preparation for this project application, he completed

multiple analyses examining associations between sleep apnea, cognitive decline, mild cognitive impairment and neuroimaging markers of vascular disease and neurodegeneration using MRI. Some of these results were presented in two presentations at the Association of Professional Sleep Societies Meeting (SLEEP 2022) in Charlotte, North Carolina. Both presentations were selected for oral/platform and poster presentations. Dr. Ramos and his team also completed analysis evaluating modifiers of sleep and cognitive decline with visual impairment findings, which were presented at the 2022 Alzheimer’s Association International Conference (AAIC) in San Diego, Ca.

S u c c e s s o f R E A C T I O N S t u d y

In 2018, Dr. Christian Camargo received a “McKnight Clinical Translational Research Scholarship in Cognitive Aging and Age-Related Memory Loss” grant from the McKnight Brain Research Foundation through the American Brain Foundation, and the American Academy of Neurology. The study Reducing the Effects of Aging on Cognition with Therapeutic Intervention of an Oral Nutrient: A Pilot Trial (REACTION) reached the completion of patient data collection in December of 2022. This grant award provided a tremendous foray for Dr. Camargo (former McKnight funded trainee and current Assistant Professorneurocognitive neurologist in the Cognitive Division) to pursue his research interest in the oral multi-nutrient Souvenaid’s ability to promote the formation of new synapses and possibly improve cognitive symptoms associated with decreased synaptic plasticity.

Dr. Camargo and the study coordinator, Marisa Modjeski, exceeded the enrollment goal and focused on subject retention and completion. The REACTION study project manager Stacy Merritt, administered all neurocognitive tests in English, while Dr. Katalina McInerney, the study co-investigator, aided in the cognitive study design and administered Spanish neuropsychological assessments. The study team overcame hurdles posed by the Coronavirus pandemic by swiftly moving to operating the study and conducting cognitive testing entirely virtually. The team personally delivered the study product Souvenaid, in many cases and the utmost precautions were taken when there was in-person communication with participants. Subjects were enrolled with a 50% chance of taking the inactive (placebo) product and felt they were volunteering to make a difference in scientific knowledge of the aging brain and the effects of Souvenaid on memory and cognition. Not only did this help foster science and to truly use the AAN/MBRF funding in the most effective way, additionally, relationships were formed with 67 study subjects who are now loyal followers of our EMBI website, social media, and community education core. They have a great interest to participate in enrolling in other brain and cognitive aging studies, particularly in the NIA Precision Aging Network (PAN) study.

I n t e r - I n s t i t u t i o n a l M e e t i n g

The 13th Annual McKnight Brain Research Foundation Inter-Institutional Meeting “Power of Precision Aging Approaches to Brain Health & Cognition” was hosted by the Evelyn F. McKnight Brain Institute at the University of Arizona, March 23-25.

We were very excited to participate in the 13th Annual McKnight Brain Research Foundation InterInstitutional meeting at University of Arizona EMBI and seeing our MBRF Trustees in-person, and colleagues and dear friends from other EMBIs Our entire EMBI core team was present at this meeting, and contributed to its great scientific success Our EMBI team conducted numerous discussions and in-person meetings with scientists and clinicians from other EMBIs, and created new collaborative team science partners We are grateful to the MBRF for sponsoring the event and to the UA EMBI for organizing and hosting it. It was a great reunion after the 2-year hiatus. Twenty UM EMBI members, collaborators and trainees attended. Five EMBI attendees were involved in the sessions as listed below.

Dr. Tatjana Rundek presented Creative Recruiting Strategies, and Successes

Dr. Susan Blanton presented Biological Clocks in Families.

Dr. Ralph L. Sacco participated in the Panel: "Next steps to make solutions for optimizing cognitive health a reality – or how to take our science out of the lab and make it useful for people.”

Dr. Christian Agudelo (McKnight Neurocognitive Scholar) presented Sleep and Cognition in Hispanic Community Health Study – Study of Latinos (HCHS-SOL)

Dr. Bonnie Levin was the moderator for the “Novel Methods for Recruiting and Retaining Diverse Participants for Studies of Brain and Cognitive Aging” session

E M B I a t A A I C

Three EMBI faculty were interviewed about their research and presentations at the Alzheimer’s Association International Conference (AAIC).

This is a prestigious achievement as the AAIC is the preeminent AD conference Dr. Rundek presented on improved cognitive prediction after inclusion of vascular neuroimaging biomarkers in the prediction models Dr. Galvin discussed building a better brain as we age Dr. Ramos discussed the relationship of sleep and neurodegeneration, and Dr. Camargo was interviewed about his clinical approach to Alzheimer’s Disease. In total, seven EMBI trainees and four faculty gave presentations.

Scientific Publications of Note in 2022

“

Stroke Genetics Informs Drug Discovery and Risk Prediction Across Ancestries”

Published online in on September 2022, Drs. Sacco and Rundek were authors on a large genomic collaborative stroke study that informs drug discovery and risk prediction across ancestries. A large international study gathering >200,000 stroke patients and >2 million control individuals from five different ancestries identified association signals for stroke and its subtypes at 89 (61 new) independent genetic loci. The study provides critical insight to inform future biological research into the pathogenesis of stroke and its subtypes. This was one of the most impactful articles published in Nature in 2022.

https://www.nature.com/articles/s41586-022-05165-3

“Associations

Between Vascular Risk Factors and Perivascular Spaces in Adults with Intact Cognition, Mild Cognitive Impairment, and Dementia”

Published September of 2022 in , the research led by Dr. Rundek, contributes to a growing knowledge of brain imaging biomarkers of aging and age-related cognitive changes As a potential biomarker, enlarged perivascular spaces around small intracerebral vessels may be an early indicator of dysfunctional transport of nutrients and clearance of waste products, which is the critical function of perivascular spaces This may be the first step in the process of neurodegeneration and other age-related brain disorders https://pubmed.ncbi.nlm.nih.gov/35871327/

“Cardiovascular Correlates of Sleep Apnea Phenotypes:

Results from the Hispanic Community Health Study/Study of Latinos”

In this article published online in the in April 2022, Dr. Ramos and colleagues reported three different subtypes of sleep apnea that are linked to cardiovascular risks among Hispanics. The team’s goal was to characterize obstructive sleep apnea phenotypes in Hispanics/Latinos and examine prevalent and incident stroke risk factors Findings in this publication are important because identifying obstructive sleep apnea phenotypes can facilitate personalized care, better inform treatment decisions, and could lead to improved clinical outcomes https://journals plos org/plosone/article?id=10 1371/journal pone 0265151

"Genome-Wide Association Study of Executive Function in a Multi-Ethnic Cohort Implicates LINC01362: Results from the Northern Manhattan Study”

Published in Neuroscience of Aging in December 2022, this research (that involved Drs Sacco, Rundek and other EMBI associates) was novel and unique as there were only few genome-wide association studies (GWAS) of executive function, and none conducted in underrepresented minority populations A GWAS composite measure of executive function that included measures of mental flexibility and reasoning using data from the Northern Manhattan Study, was done on a racially and ethnically diverse cohort (N=1077, 69% Hispanic, 17% non-Hispanic Black and 14% non-Hispanic White) Four SNPs located in the long intergenic non-protein coding RNA 1362 gene, LINC01362, on chromosome 1p31 1, were significantly associated with the composite measure of executive function in this cohort (top SNP rs2788328, ß=0.22, p=3.1×10−10). The data showed that when using a diverse sample from three race/ethnic groups, evidence was found for common variants on 1p31.1 to be significantly associated with a composite measure of executive function. Further investigation into the role of this region in executive function is warranted. https://www.sciencedirect.com/science/article/abs/pii/S0197458022002524

“Patterns of Healthcare Use and Mortality After Alzheimer's Disease or Related Dementia Diagnosis Among Alaska Native Patients: Results of a Cluster Analysis in a Tribal Healthcare Setting”

This paper published in in July 2022 reports on research done by Dr. Galvin and colleagues on Alaska Natives and American Indians (AN/AI), who now represent a rapidly aging population with disproportionate burdens of Alzheimer's disease and related dementias (ADRD) risk factors The study objective was to characterize healthcare service use patterns and mortality in the years following ADRD diagnosis for patients in an Alaska Native Tribal health system The study sample included all AN/AI patients aged 55 or older with an ADRD diagnosis who were seen between 2012-2018 (n = 407) Cluster analysis was used to identify distinct patterns of healthcare use for primary care, emergency and urgent care, inpatient hospital stays and selected specialty care. They compared demographic and clinical factors between clusters and used regression to compare mortality. Results indicated that those receiving the most services had the greatest healthcare-related needs and increased mortality. Future research could isolate factors that predict service use following ADRD diagnosis and identify other differential health risks. https://pubmed.ncbi.nlm.nih.gov/36072365/

“Validity of the NIH Toolbox Cognitive Battery in a Healthy Oldest-old 85+ Sample”

This is one of the first McKnight Brain Aging Registry (MBAR) papers with others to be submitted and/or published It was written by several of our MBAR researchers including Drs. Rundek and Levin, and was published online (ahead of print) in 2022 This paper is novel in its discussion of an important research tool being tested in an over 85 cohort The research concluded that the NIH Toolbox Cognitive Battery (NIH TB-CB) is a valid assessment for the oldest-old samples, with

relatively weak validity in the domain of executive functioning. This cohort’s ability to use a computer may impact composite scores, possibly due to the executive demands of learning to use a tablet. Strong relationships of executive function with other cognitive domains could be due to cognitive dedifferentiation Overall, the NIH TB-CB could be useful for testing cognition in the oldest-old and the impact of aging on cognition in older populations https://www cambridge org/core/journals/journal-of-the-international-neuropsychologicalsociety/article/validity-of-the-nih-toolbox-cognitive-battery-in-a-healthy-oldestold-85sample/65D80CA089651B24321E21D8606ABEA6

“Vascular Cognitive Impairment (VCI)”

This important review paper in Neurotherapeutics co-authored by Drs. Rundek, Tolea and Camargo among others, was issued in January of 2022. It presents recent developments in age-related vascular cognitive impairment (VCI), its mechanisms, diagnostic criteria, neuroimaging correlates, vascular risk determinants, and current intervention strategies for prevention and treatment of VCI. It also summarizes the most recent and relevant literature in the field of VCI. It concludes that VCI clinical and scientific framework that accounts for complexity of vascular factors and overlaying diagnoses will help drive translational research for improved understanding and ultimately lead to effective prevention and treatment of VCI in clinical practice. https://pubmed ncbi nlm nih gov/34939171/

The University of Miami (UM) led by Dr. Galvin uses a screening tool, the Brain Health Platform to identify Alzheimer’s risk with patients and research participants at the Comprehensive Center for Brain Health and relies on the following assessments to determine someone’s brain health and future risk; the Resilience Index, a measure of risk of ADRD, the Vulnerability Index and the Number-Symbol Coding Task, a measure of brain performance. Results showed that the Brain Health Platform can effectively and accurately identify even the very mildest impairments due to ADRD, leveraging brief yet powerful and actionable indices of brain health and risk that could be used to develop personalized, precision medicine-like interventions This study is discussed in the Journal of Alzheimer’s Disease in (in press)

“The Brain Health Platform: Combining Resilience, Vulnerability, and Performance to Assess Brain Health and Risk of Alzheimer's Disease and Related Disorders”

“Age-related Focal Thinning of the Ganglion Cell-inner Plexiform Layer in a Healthy Population”

Published in June, 2022 in Quantitative Imaging in Medicine and Surgery, our EMBI neuroophthalmologists Drs. Jiang, Wang, Rundek, Levin and colleagues wrote about their research exploring changes to the retina as an early biomarker of the aging process Learning the underlying age-related biological phenomena is important to improve the understanding of the ageing process

This is the first study to apply UHR-OCT for visualizing the age-related alteration of intraretinal layers in a general population The most profound change of the optic nerve fiber is an oval-like focal thinning in GCIPL, which occurred in the inferior sector within the inner annulus and was strongly related to increased age https://qims amegroups com/article/view/92965/html

“Structural Basal Ganglia Correlates of Subjective Fatigue in Middle-Aged and Older Adults”

Led by Dr. Levin and her trainee Nik Banerjee, this research on structural basal ganglia correlates was published in December 2022 in the Journal of Geriatric Psychiatry and Neurology It is significant because fatigue is highly prevalent in all phases of aging and is understudied This study is among the first to show that reduced basal ganglia volume is an important neurostructural correlate of subjective fatigue in physically able middle-aged and older adults without neurological conditions

https://journals sagepub com/doi/10 1177/08919887211070264

We are a Collaborative Integrative Translational Trans-disciplinary Institute (CITTI) of over 100 clinical and translational scientists dedicated to translating discoveries into interventions to reduce agerelated memory loss and improve brain health in partnership with communities

Our EMBI places an emphasis on the strengths of our research training and clinical team in close integration with our programmatic clinical activities through our Clinical Cognitive Division (Dr Galvin, Director), Memory Clinic (Dr Baumel, Lead) with the Department of Psychiatry's CNSA (Dr Loewenstein, Director, and Drs Crocco and Curiel, Co-directors), the Comprehensive Center for Brain Health (Dr Galvin, Director) and Schoninger Neuropsychology program (Dr Levin, Director), which fosters effective research translation strategies for early diagnosis, treatment and prevention of agerelated memory loss and cognitive decline.

Dr. Galvin has been appointed Director of the Cognitive Division this year to lead our clinical team in the cognitive division in collaboration with EMBI Our clinicians are Dr Bernard Baumel, Lead of the UM Memory Program, Dr Xiaoyan Sun, Educational Director and Co-Director of the UM Brain Endowment Bank, Dr Christian Camargo our AAN/MBRF Scholar, and Dr Michelle Marrero, a former EMBI Clinical Fellow. Our clinical training and educational program in aging and age-related cognitive impairment of our EMBI is housed in the Cognitive Division of the Department of Neurology.

Comprehensive Center for Brain Health

Dr. Galvin is the EMBI Cognitive Division Director, and Director of the Comprehensive Center for Brain Health (CCBH). His CCBH is fully operational now, with staff, clinicians and trainees totaling almost 30 individuals. This officially extends our cognitive aging scope of scientific research, clinical care, and ability to make an impact on, and to influence patients and community members from the Florida Keys to Boca Raton and the Palm Beaches Dr Galvin was named the Alexandra and Bernard Schoninger Endowed Chair in Memory Disorders The ceremony will take place on January 19, 2023 The Schoningers were home builders and shopping center pioneers whose children attended University of Miami and thus were delighted to make gifts to the University that went further through other matching gifts This gift was matched by the MBRF gift in 2014, creating the Evelyn F. McKnight Endowed Chair for Learning and Memory in Aging that Dr Rundek holds, as well as the Schoninger Endowed Chair in Memory Disorders that is held by Dr Galvin

C O G N I T I V E D I V I S I O N I N T H E D E P A R T M E N T O F N E U R O L O G Y

Schoninger Neuropsychology Program

Led by Dr. Bonnie Levin, the Schoninger Neuropsychology Program provides a full range of interventions designed to mitigate age-related memory loss and other cognitive changes associated with the aging process Used in conjunction with neuropsychological testing to identify areas of cognitive weakness, patients are offered a uniquely tailored program to address their specific needs in areas that offer potential for intervention This precision-based delivery of services focuses on developing realistic goals and practical, accessible plans of action A major strength of the program is that nearly all of the interventions can be administered via a virtual platform or face-to-face meetings Dr. Katalina McInerney is an instrumental part of the program She sees patients clinically as well as participates in research projects She contributes to clinical trials spanning from administering neuropsychological tests and tracking/monitoring the cognitive abilities and mood of participants on large sponsored clinical trials and assists in the design and implementation of site initiated clinical trials. The program has seven faculty who see patients, four fellows and ten practicum students. A main research focus of the Schoninger Program is to investigate and mitigate frailty-associated risk of cognitive decline through the Frailty Research Program that collects information for the Frailty Registry. The Frailty Registry database currently has over 500 participant records with over 100 individual-level variables.

Center for Neuroscience and Cognitive Aging (CNSA)

Led by Dr. David Loewenstein, the CNSA includes Dr Curiel, a recognized minority leader in AD clinical research and Diversity Core Lead of the 1FL ADRC, and the CNSA Medical Director, Dr. Elizabeth Crocco, who is a recognized clinical AD investigator and Chief of Geriatric Psychiatry This Center’s mission is to be a national and international leader in understanding the aging brain and a hub to develop and implement the most state-of-the-art techniques for the study of brain disorders

The CNSA is grounded upon three pillars: research, clinical care and education Their scientists are leaders in the development of cutting-edge methodologies to diagnose and treat cognitive disorders In 2022, the CNSA and EMBI continued as collaborators on the 1FL ADRC and continued to meet regularly on the translational vascular imaging projects VIP and IMAGINE

Brain Endowment Bank

The Department of Neurology Brain Endowment Bank™, led by Dr. William Scott and Dr. Xiaoyan Sun (is one of six NIH designated NeuroBioBank brain and tissue biorepositories in the nation with a large AD/ADRD and control brain repository from diverse populations The Brain Endowment Bank encourages brain donation to support medical and scientific researchers, who study the human brain in search of better medications and treatments, and ultimately a cure for brain diseases and disorders EMBI and the Cognitive Division participate and support collaborations with this outstanding UM Neuroscience Program including Drs. Regina Vontell and David Davis. Dr. Sun will take on a role requiring more responsibility at the NeuroBioBank in 2023, including the coordination of brain cutting sessions for EMBI Members and Collaborators. Both Dr. Vontell and Davis’s grants in 2022 are listed on pages 50 and 52. Dr. Davis completed an important manuscript describing environmental exposure to atmospheric BMAA in olfactory tissues in Alzheimer's disease patients that was submitted to the journal Toxicology Reports.

The world-renowned UM Bascom Palmer Institute (BPI) has been ranked the #1 eye hospital in the country by the US News & World Report’s Best Hospitals issue for the 20th time this year BPI faculty, Drs. Hong Jiang and Jinhua Wang (Mentor/Faculty) are active EMBI members with a research focus on ocular biomarkers of cognitive aging and dementia They collaborate with Dr Rundek on microvasculature and microcirculation changes and with Dr Galvin on retinal amyloid imaging in brain aging, MCI and AD/ADRD They are also Co-Investigators with Dr Signorile from the Director of the Laboratory for Neuromuscular Research and Active Aging on the pilot study Circuit Resistance Training and Retinal Vascular Changes in Older Persons Drs Jiang and Wang have a collaborative grant with the UAB EMBI that is listed in the collaborative programs with other McKnight Institutes section

The UM Clinical Translational Science Institute (CTSI), led by Dr. Sacco is a university-wide institute dedicated to accelerating and transforming culturalized clinical translational (C/T) science and serves as the Miami Hub of the national CTSI consortium to advance scientific discoveries into improved health. The CTSI together with its programs (biostatistics, epidemiology and research design; informatics and data science; community and stakeholder engagement; team science; integrating special population; regulatory, network capacity, translational workforce development, KL2, and pilot program) provides infrastructure and resources for C/T research and clinical trial readiness to address new pandemics or emergencies and support education, training and diverse translational workforce development (TWD)

Dr. Rundek is Director of the CTSI KL2 Program and is Director of a MS degree in Clinical Translational Investigation (MCSTI), a highly integrated, cross-disciplinary program to train the next generation of translational scientists-leaders Dr Rundek participated in the CTSI renewal and submitted a CTSI K12 program grant to build upon the 10 years of success in her prior CTSI KL2 leadership, where she trained 21 Scholars who have 176 publications directly related to their KL2 projects and successfully competed for over $50M in research funding Consistent with the overall CTSI theme, half of the KL2 scholar research projects were on minority health and health disparities A new proposed CTSI K12 program will develop a robust, broad clinical translational workforce of diverse scientists who are not only domain experts but also bring a more nuanced, systems-level understanding of translational research and dissemination and implementation science to improve the health of our community, address health disparities and promote health equity.

Frost School of Music

The Frost School of Music at the University of Miami is one of the most highly acclaimed innovative music schools in the United States It is a progressive school that fosters students to build themselves into self-assured music professionals Its award-winning faculty vigorously and effectively seeks to improve the world through ardent musical performances, impactful research, and exceptional teaching Drs. Theresa Lesiuk, Xiaoyan Sun, Bonnie Levin and Roger McIntosh collaborated on the project The Neural Network Connectivity of Autobiographical Music in Adults with Mild Cognitive Impairment and Mild Alzheimer’s Disease. The aims of the project are to investigate the activated neural networks of autobiographical versus novel music in the patients with Mild Cognitive Impairment (MCI) and mild Alzheimer’s disease (mAD). The study uses a within-subjects and between-subjects design with 24 participants with MCI/mAD and a control group of 10 cognitively normal controls The three conditions (i e , recorded autobiographical music, novel music, white noise) will be randomly counter-balanced This will foster significant collaborations with the arts and cognitive aging

OneFlorida ADRC (1FL ADRC) continues to operate under the leadership of Dr. Loewenstein, one of the 1FL ADRC Directors Dr. Rundek serves as Co-Director of 1FL ADRC REC AlzSTARS (Alzheimer’s Science Training to Advance Research Success) together with Dr Glenn Smith from UF Two AlzSTARS post-doctoral graduates are part of EMBI, Magdalena Tolea, CCBH and Regina Vontell, UM Brain Endowment Bank Together with 1FL ADRC, UM has a strong national presence in AD/ADRD genetic research, particularly in minority populations though the Hussman Institute for Human Genomics (HIHG).

Hussman Institute for Human Genomics (HIHG) is led by Dr. Margaret Pericak-Vance. HIHG is leading a national initiative in the whole genome sequencing for ethnically diverse AD cohorts and the project on the origin of AD in people of African Ancestry. The HIHG received a National Human Genome Research Institute (NHGRI) and NIA grant of over ten million dollars to focus on individuals with mixed genetic backgrounds. This research champions UM’s commitment to diversity and hemispheric collaborations. Dr. McInerney, part of the Schoninger Neuropsychology Program, is a neuropsychologist on the Whole Genome Sequencing in Ethnically Diverse Cohorts for the Alzheimer Disease Sequencing Project Follow-up Study focusing on adjudication, harmonization and training efforts aimed at better understanding the role of genetics in Alzheimer's disease in diverse populations

The Peritz Scheinberg Cerebral Vascular Disease Research Laboratories

The laboratories continue to conduct research on cerebral circulatory control mechanisms in animal models which have evolved over the years into studying cerebral ischemia from molecular biology to physiology and behavioral testing, with the goal of finding novel therapies. Their scientists are constantly in search of novel findings, seeking to expand the knowledge of cerebrovascular disorders with the aim to treat and enhance quality of life. Dr. Perez-Pinzon, Dr. Rundek, along with Dr. Young collectively made scientific headway with the project Investigation of the Impact of Capillaries and Neutrophils to Blood Flow Changes in a VICD Model and Mixed AD Model. Dr. Dave is a Research Associate Professor whose research includes studying potential signaling pathways responsible for neuronal death in neurodegenerative diseases, especially cerebral ischemia. He received an award from the Journal Stroke, co-authored several publications and was part of several abstract/poster presentations at scientific meetings Dr. Raval co-authored 9 manuscripts in 2022 and authored several abstracts/posters accepted at scientific meetings and conferences Dr. Pinto is an assistant research professor who has been involved in understanding the possible neuronalspecific role of mitochondrial dysfunctions and mitochondrial DNA deletions and depletion in different mouse models of aging and neurodegenerative diseases Dr. Oliver Bracko, our most recent scientist collaborator, received three grants including 1 NIH co-authored 2 publications and gave 5 presentations at scientific meetings

We continued to fulfill our mission and vision via our ongoing partnerships and collaborations in 2022. This illustration captures the expansive reach of our cross departmental and disciplinary relationships, which truly enhance our EMBI.

We maintained working relationships and collaborations with our key and enduring programs, solidified existing ones and developed new ones. Here is an overview of our closest programmatic ties.

Our New Partners in Research and Training in 2022

Precision Aging Network

While in 2019, our EMBI received support from the MBRF to work on a pilot project to gather data to support the University of Arizona’s U19 grant submission led by Dr Carol Barnes, the official and in depth partnering began this year In late 2021, NIH awarded a $60 million grant for the multicentered Precision Aging Network (PAN) Since then and throughout 2022, we have been deeply involved in setting up the Precision Aging Network (PAN) research infrastructure, IRB, protocols, SOPs and other activities at UM for this complex research program. It is a partnership focused on sustaining healthy minds for life. PAN’s approach is to discover personalized solutions to improve brain health and has partnered with the NIH MindCrowd program. MindCrowd is the first crowd sourced scientific research project to understand how the brain ages to prevent diseases like dementia and is seeking to enroll one million people to take an online memory and attention test. The PAN project seeks to learn key drivers of healthy brain functioning through the aging process, how to achieve optimal brain function across the life span, and how researchers can help to predict, prevent or slow unwanted age-related changes in brain and cognitive health Dr. Rundek is the Site PI and PAN Clinical Project 2 Co-Director with Dr Lee Ryan from UA Dr. Levin is a Co-Investigator at the UM site Our site also has an extensive team that includes Susan Fox-Rosellini, Marti Flothmann, Digna Cabral, Anara Feal Rodriguez, Marisa Modjeski and Stacy Merritt

Launch of PAN at UM

We had a successful launch of the Precision Aging Network (PAN) project at our EMBI, led by Drs. Rundek and Levin. A team of 10 embarked on this endeavor for over a year to get it off the ground. With this tremendous team effort that included multiple moving parts such as weekly meetings with the lead site, internal weekly meetings, regular communication and scientific meetings, an in-person meeting at UA, in-person training meetings at UM, local and central IRB submissions and approvals, biospecimen processing and storage arrangements, acquisition of study space, state-of-the art MRI protocols and ultrasound neurovascular imaging, and so much more. Dr. Rundek, leader of the Carotid Ultrasound Core study-wide, organized and hosted a training at our site for all clinical sites (Emory, Georgia Tech, Johns Hopkins, UA, and UM) She gave a presentation on the history and technology of carotid ultrasound imaging The training involved demonstrations by the lead ultrasound technician, training in performing standardized and validated ultrasound protocols in which all sonographers were trained and certified to perform the scanning according to the research protocols Rigorous QC and adherence with the protocol measures are in place, and re-training planned if needed We have started enrollment at UM, with our first participant enrolled on December 20, 2022

Movement Disorders Division

Dr. Ihtsham Haq is Director of the Movement Disorder Division at UM Department of Neurology and a new collaborative researcher in our EMBI His overall research interest has been in understanding and improving the care of patients with movement disorders and Lewy Body Dementia with a focus on technology and brain circuitry One of his priorities is to take concrete steps to ensure historically underrepresented patients are provided an opportunity to participate in research at UM, including pipeline programs, advocacy and disparity research He has been an important collaborator with our imaging pipeline initiative and meets regularly with the EMBI team regarding the two funded research projects funded by FL Department of Health (Dr. Rundek PI on both), Carotid Ultrasound Imaging Markers o AGINg and Endothelial function in Risk of Alzheimer’s Disease The Florida IMAGINE Study of AD Risk (VIP); and Caroti Ultrasound Imaging Markers of AGINg and Endothelial function i Risk of Alzheimer’s Disease: The Florida IMAGINE Study of A Risk (IMAGINE) study. He has been a terrific collaborator and mentor to our PhD student and junior faculty on the researc projects and has contributed greatly to moving these project ahead He joins us in this multi-disciplinary collaboration including the Center for Cognitive Neuroscience and Aging, th Department of Radiology and Biomedical engineering Dr Ha was recently named the Cornfeld-Hurowitz Endowed Chair of Movement Disorders

Center for Translational Sleep and Circadian Sciences in the UM Department of Psychiatry Dr. Girardin Jean-Louis, Director of this recently established center, is a newly recruited leader in sleep science at UM He comes from NYU and brings unique expertise to this partnership with EMBI EMBI has established a solid collaborative program with him and his team The vision of the Center for Translational Sleep and Circadian Sciences is to serve as a collaborative learning laboratory and a university-wide resource to stimulate, support and evaluate high-priority research in sleep and circadian sciences His Translational Circadian Sleep Laboratory (TCSL) focuses on translational mechanistic studies of sleep and circadian disruption in AD/ADRD pathogenesis and cognitive function, with a particular focus on minority populations and health disparities. As a leader of the NIH Program to Increase Diversity Among Individuals Engaged in Health-Related Research (PRIDE), Dr. Jean-Louis puts health disparity research and training of underrepresented minorities on the frontline at UM. PRIDE is a national stewardship program for training of minority post-doctoral and junior faculty investigators in translational science. While at Columbia University, Dr. Rundek was a lecturer and a mentor in the PRIDE program. As Dr. Jean-Louis brought PRIDE to UM, Dr. Rundek will participate again in PRIDE as an investigator and a mentor.

Immediately upon arrival to Miami, Dr. Jean-Louis continued collaborating with Dr. Rundek and became one of our new EMBI collaborators. Together, they have already submitted three training grants to NIH as MPI, specifically geared toward training and recruiting future minority scientists: two T32s and one R25 From the aspects of structure, organization and data collection needed for successful submission, these are the most challenging and extensive grant types to prepare

The first T32 training grant submitted to the NIH’s National Heart, Blood and Lung Institute (NHBLI), received a fantastic score and has been accepted for funding. The Promoting Academic Workforce Diversity in Translational Behavioral and Cardio-Metabolic Research-PINNACLE project will train, mentor and sustain a network of twelve underrepresented minority post-doctorate trainees committed to developing independent academic careers in translational and behavioral

cardiovascular health research This will have a strong impact in achieving the national mandate (Healthy People 2030) to increase diversity in the academic workforce, thus expanding capacity to implement translational models to improve health quality and equity. PINNACLE will begin the first trainee enrollment in January 2023.

The second training program grant, a T32 was submitted to the NIA, Cross-disciplinary research opportunity for training in AD/ADRD science-CrossROADS. It is a 2-year program for MDs and PhDs with the overall goal to increase the number of diverse AD/ADRD investigators-leaders in crossdisciplinary clinical and translational (C/T) research, who can 1) effectively and rapidly disseminate, implement and translate discoveries to practice and community and 2) address the special health challenges and health disparities of the diverse AD/ADRD patients we serve through team science and collaborations in partnerships with AD/ADRD community partners and diverse health care stakeholders While this T32 is a great program with many resources and partnerships to make it successful, it was not funded on the first submission and will be resubmitted in May 2023

The third training grant Dr Rundek submitted with Dr Jean-Louis was an NINDS-R25 program in neuroscience research titled Congruent Mentorship to Reach Academic Diversity In Neuroscience Research-HARNESS The HARNESS Program aims to select qualified under-represented minority postdoctoral PhDs and MDs with great potential to contribute to current knowledge of evidencebased neuroscience models to study neurological diseases The program mentors would increase trainees’ self-efficacy to pursue an academic career that will be achieved via mentoring and active coaching to acquire expertise in behavioral neuroscience and health equity. Trainees would be given intensive individualized training and guidance in grant writing to acquaint them with the NIH review process. This grant application is pending NIH review.

The University of Miami Center for AIDS Research (CFAR) is the first NIH-funded AIDS research center in Florida. The US south is disproportionately impacted by HIV and Florida has the highest number of new HIV diagnoses in the country The Miami CFAR is poised to make a difference with a multipronged approach to combat the HIV epidemic: to provide scientific leadership, to foster integration of basic, clinical, and behavioral/social HIV/AIDS research, and to fill recognized gaps in research and practice

Dr. Rundek’s collaboration with CFAR will formally continue as its funding was just renewed for another 5 years She will continue to be a co-leader of the CFAR Scientific Working Group (SWG) on Aging in HIV and serves on the Steering Committee as a senior investigator in aging research. In this role, she provides leadership, expertise, and mentorship in aging and age-related HIV neurological comorbidities. The goal of a SWG is to promote multi-disciplinary collaborations that result in successful applications for new HIV/AIDS research awards. Through EMBI, she also provides opportunities to HIV investigators at every stage of their career level to utilize infrastructure and resources of EMBI, including the opportunities to obtain the EMBI pilot awards in cognitive aging.

The HIV and Aging SWG was organized in February 2019 to meet the needs of an underrepresented area of research A HIV and Aging symposium held December 2019 by the SWG further linked the CFAR with the other centers and institutes on campus, drawing audience participation from the Evelyn F McKnight Brain Institute, Miami CTSI, FDOH, the SCCC and the Community Co-Leaders: Drs Suresh Pallikkuth, Tatjana Rundek, and Emmanuel Thomas

Training

Dr. Rundek’s dedication to training and mentoring along with the EMBI’s integration of clinical, translational and basic science sets the stage for our mission to train future clinicians and scientists in age-related cognitive decline She continuously sought new training grant opportunities and announcements throughout the year She submitted five training grants to NIH this year, of which two were funded (T32 and FL DOH), one will be re-submitted, and two are awaiting scoring details (NINDS R25 and NCATC CTSI K12) Three were in collaboration with Dr Jean-Louis which are discussed above on pages 31. One was an application to the Florida DOH Ed and Ethel Moore Alzheimer’s Disease Research Program, that was just awarded in December 2022

EMBI leaders Drs. Rundek, Sun, Levin and Galvin along with our EMBI collaborators have been mentoring promising junior faculty and students throughout the year. See Appendix 1 training tables on pages 60-62.

CHRISTIAN AGUDELO

ANITA SAPORTA

SONYA KAUR

SARAH GETZ

REGINA VONTELL MAGDA TOLEA

Christian Agudelo, MD is our EMBI Neurocognitive Scholar (Mentors: Drs. Rundek and Ramos). Dr. Agudelo is a neurologist with a sleep and cognitive fellowship. He has been a model scholar, actively working on grant applications, publishing papers from his research, and participating in education and community outreach efforts He has been successful in obtaining a NIH Diversity Supplement to his mentor’s (Dr Alberto Ramos) NIH R01 grant, Sleep in Neurocognitive Aging and Alzheimer’s Research (SANAR) with funding staring in January 2023 His accomplishments in 2022 are detailed in Appendix 5, pages 87-95

Anita Seixas Dias Saporta, MD (Mentor: Dr Rundek), is trained in neuroimaging research in multimodalities (mainly MRI and PET) She oversees the post processing of MRIs and medical data for subjects enrolled in the Schoninger Frailty Database led by Dr. Levin. This Registry has detailed medical and neuropsychological data of subjects seen in Dr. Levin’s clinic with memory complaints. Anita collaborates on two projects led by Dr. Rundek. The Carotid Ultrasound Imaging Markers of AGINg and Endothelial function in Risk of Alzheimer’s Disease: The Florida IMAGINE Study of AD Risk is currently in the collection and data processing stage. She quantifies silent cerebrovascular disease related lesions, such as white matter hyperintensities and enlarged perivascular spaces. She is in the data analysis stage for publications and generation of pilots for novel projects for the Brain Vascular Imaging Phenotypes, Vascular Comorbidities, and the Risk for Alzheimer Disease: The Florida VIP Study of AD Risk. She has collaborated on three published papers this year and one that is in press

Sonya Kaur, PhD (Mentors: Drs Rundek and Levin) is an Assistant Professor in the Department of Neurology Division of Neuropsychology Schoninger Neuropsychology program Her research focuses on mechanistic pathways that mediate cognitive impairment in aging She has a special interest in examining the impact of lifestyle interventions (e g exercise, sleep) on markers of disease progression in a variety of neurodegenerative processes This year, she applied for three grants 1) McKnight Inter-Institutional Pilot award, 2) Florida Department of Health (DOH) pilot award and 3) the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Scholar’s program. She contributed to the EMBI community outreach program by presenting on sleep and aging and has written a sleep blog on the EMBI website. She has also co-authored six publications in 2022. Two of them are from collaborations made in the American Academy for Sleep Medicine SOAR program. This collaboration has resulted in to two co-authored publications in the area of sleep, vascular risk factors and Alzheimer’s Disease biomarkers in older adults without cognitive impairment.

Regina Vontell, PhD, MA (Mentors: Drs. Sun, Scott, and Rundek) is a Research Assistant Professor and Associate Director of the Brain Endowment Bank Her primary research has focused on the inflammatory mediators in the brain and their relation to complex diseases She has been instrumental in studies that identify potential targets for neuronal inflammation This year she received funding for three projects she will be an Investigator on and submitted the manuscript Inflammasome Signaling Proteins in Neurons and Microglia in Early, Intermediate Stages of Alzheimer’s Disease to the journal Brain Pathology and co-authored and presented abstract/poster presentations at important scientific meetings She was interviewed for her presentation at the 2022 AAIC She also led the Open Scope Presentation, What to Do With p62 and led a Student Tour and Brain Dissection.

Magda Tolea, PhD (Mentors: Drs. Galvin and Rundek) is a Research Assistant Professor at the UM Comprehensive Center for Brain Health (CCBH) where she is the Associate Director of Research Her current research focuses on the intersect between physical dysfunction and cognitive impairment, more specifically on sarcopenia and its role as a potential predictor of cognitive decline and dementia in later life In 2022 she spent time opening the Research Center at the CCBH and preparing for a new NIH/NIA R01 drug trial that she is the Site PI and Co-Investigator on, Mild to Moderate Dementia with Lewy Bodies. She completed her analysis for Aim 1 of her ADRC AlzSTARS project focused on the cross-sectional relationships of sarcopenia and cognitive performance in cognitively normal but at-risk older adults. She submitted a manuscript to the Journal of Alzheimer’s Disease Reports and went through two rounds of revisions. She serves on a dissertation committee for a PhD candidate.

Lilah Besser, PhD, MSPH (Mentor: Dr. Galvin) is a Research Assistant Professor at the UM Comprehensive Center for Brain Health (CCBH). Her current research centers on the intersections between neighborhood built and social environments, healthy aging and brain health. She is the Principal Investigator on two grant-funded projects: Longitudinal Associations Between Neighborhood Greenspace and Brain Aging in Cognitively Normal Older Adults and Neighborhood Segregation and Longitudinal Change in Brain Health Measures She received funding this year to study three different projects from 1) Alzheimer’s Association, 2) NIH and 3) C4R Early Investigator Award She published a paper in a high impact journal on neighborhood segregation She is Co-I on NIH/NIA R01 grant application submitted in November 2022. She co-chaired two Structural/Social Determinants of Health work group for Social/Structural Determinants of Health Working groups for the 1) Multi-Ethnic Study of Atherosclerosis and 2) Diversity and Disparities Professional Interest Area for the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART). She presented at multiple conferences/meetings.

Michael Kleiman, PhD (Mentor: Dr. Galvin) is a Postdoctoral Fellow and Data Scientist at the UM Comprehensive Center for Brain Health (CCBH). Dr. Kleiman’s area of focus is on the intersection between neurology, cognitive psychology and data science. He has developed tools and machine learning models that use neurobehavioral markers as well as health records, cognitive exam scores and neuroimaging data for assessing current impairment and predicting future risk of impairment This year, he began collecting data for the Behavior-based Automated Cognitive Assessment of Neurodegeneration (BACAN), which examines both gaze and speech behavior to measure cognitive domain performance within prodromal and preclinical Alzheimer’s disease He was a recipient of an Alzheimer’s Association International Research Grant and awarded the McKnight Clinical Translational Research Scholarship in Cognitive Aging (See Honors and Awards section on pages 49-50)

Taylor Ariko, BS (Mentors: Drs. Rundek and Zhao) is a PhD Student in the College of Biomedical Engineering and is our EMBI trainee. She has been instrumental in working with the DOH IMAGINE Study (Rundek PI) and has been working on the MRI post-processing pipeline under the supervision of the study physicist. She programed and coded the pipeline for WMHV and DTI image sequences and processed the images. She has also been trained to perform carotid ultrasounds. This year she co-authored three publications. She presented her work at four University of Miami scientific forums, co-authored one abstract/ poster for the 2022 AAIC and submitted three abstracts for the 2023 American Academy of Neurology (AAN) meeting

Botagoz Aimagambetova, MD (Mentors: Drs Rundek and Tulay) completed an MD degree and a residency in medicine/cardiology in Kazakhstan She has studied ultrasound and functional evaluation of cardiovascular diseases and is trained in a full range of noninvasive diagnostic cardiac exams She is currently working on a Master’s in clinical and translational research at the University of Miami (Program Director, Dr. Rundek). Her primary research interest is the determination of cardiovascular risk factors in the etiology of neurodegenerative processes in an elderly population. Her current research which is a registered protocol for a systematic review is “How arterial stiffness measured by pulse wave velocity correlates with cognitive decline in hypertensive individuals?” The research part of the review through the PubMed, Web of Science, Embase, Scopus, and CINAHL databases with the UM Calder Library system is complete She submitted an abstract to the 2023 American Academy of Neurology (AAN) Conference titled Estimated Pulse Wave Velocity Inversely Associates with Cognition in the Northern Manhattan Study She also submitted an abstract to the 2023 UltraCon powered by AIUM titled The Role of Beta-Stiffness Index and Estimated Pulse Wave Velocity in Cognitive Aging

Nicole Dueker, PhD (Mentors: Drs. Wang, Blanton, and Rundek) is a research scientist at UM and is an EMBI trainee. She performs statistical and genetic epidemiological analyses in various datasets, including the Northern Manhattan Family Study, UK Biobank, ADNI and others. Her primary work focuses on performing analyses on and investigating the relationship between epigenetic age acceleration and stroke intermediate phenotypes as well as epigenetic changes and their association with carotid bifurcation in a large sample of extended families from the Dominican Republic She also contributes to grant writing for proposals involving the family study dataset as well as developing her own independent grants A manuscript was accepted for publication in the journal Neurobiology of Aging She presented an awarded poster at the American Society of Human Genetics (ASHG) this year She submitted an R03 to the NIA which was scored but not funded (Genetic Variation in Social Connectivity and its Association with MCI and AD/ADRD) and will be resubmitted in 2023. She co-taught a course in the PhD in Genetics- HGG621: Design & Analysis of Human Genomic Studies.

Sarah Getz, PhD (Mentors: Drs Galvin and Levin) is an instructor at the Comprehensive Center for Brain Health (CCBH) She has been working on her Neurocognitive Correlates of Scam Susceptibility in Age-Related Hearing Loss project funded by the McKnight Brain Research Foundation through the American Brain Foundation and the American Academy of Neurology. She was a recipient of an Alzheimer’s Association International Research Grant. (See Honors and Awards section on page 49) She submitted a K01 grant this year which was scored 8 points below the payline. Drs. Wilson and Grilli from the University of Arizona EMBI are both external advisors for the application that she will resubmit in 2023. There is a patent pending with an assessment she has created along with Dr. Levin.

Scientific Education

On October 21st we had a special Grand Rounds guest speaker as a collaboration with the UF Evelyn F. and William L. McKnight Brain Institute. Dr. Eduardo Candelario-Jalil, Associate Professor in the Department of Neuroscience presented “Multipronged Approaches to Targeting Neuroinflammation and Blood-brain Barrier Damage in Ischemic Stroke ”

The EMBI monthly seminar series featured:

Oliver Bracko, PhD "Contribution of Neutrophils to Microvascular (dys)function" January 26th, 2022

Teresa Lesiuk, PhD, MT-BC “Music Training for Cognition Enhancement in PD” February 23, 2022

Karen Nuytemans, PhD “Genetic Studies in Dementia Across Ancestries" March 9th, 2022

Alex Horenstein, PhD "Mobile Experiments: Method and Application(s)" April 13th, 2022

Ayham Alkhachroum, MD, MSc "Biomarkers of Consciousness Recovery After Acute Brain Injury" May 18th, 2022

Lilah M Besser, PhD, MSPH "Neighborhood Greenspaces and Cognitive and MRI Outcomes in Older Adults" June 8th, 2022

Ekaterina Denkova, PhD "Investigating Brain Network Configurations During Rest and Task with Frequent Mind Wandering" August 10th, 2022

Christian Agudelo, MD "Gray Matter Microstructure as a Sleep Apnea Related Marker of Cognitive Decline" September 21st, 2022

Danylo Cabral, PT, PhD "Exercise for Brain Health: Investigations into the Underlying Mechanisms of Neuroplasticity and Cardiovascular Health in Aging Adults" October 12th, 2022

UM Medical Residents Journal Club Collaboration with EMBI

McKnight Cognitive Resident Journal Club - Ritwik Bhatia, MD "Association Between TBI-Related Hearing Impairment and Cognition: A TRACK-TBI Study" January 27th, 2022

McKnight Cognitive Resident Journal Club - Lisa Surowiec, MD "Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality" April 22nd, 2022

McKnight Cognitive Resident Journal Club - Jude Charles, MD "Rapidly Progressive Dementia: When to Suspect Autoimmune Encephalitis" September 14th, 2022

UM Department of Neurology Grand Rounds

Bonnie Levin, PhD "The Diagnostic Dilemma of MCI: The Case for a More Complex Phenotype" November 18th, 2022

Medical Resident and Fellow Training

Crucial to the field of aging, Dr. Crocco our EMBI collaborator from the CNSA has an intensive involvement in the training of the Jackson Memorial and University of Miami fellows and residents each year. She provides training to fellows and residents specializing in aging, which is especially important as there is a great need for clinicians in the field of aging. Although her case conferences and other training offerings are organized for psychiatry residents and fellows, our neurology trainees are invited We hold quarterly neurology-psychiatry collaborative educational sessions and grand rounds

Here is an overview of her training.

She holds Weekly Case Conference for the JMH Geriatric Psychiatry Training Program and coordinates and supervises all geriatric psychiatry fellows’ weekly presentations of patient’s case history, including biological, psychological and sociological data and formulates an integrated treatment plan.

She leads JMH Geriatric Psychiatry Residency Training Program Weekly Journal Club consisting of weekly coordination and supervision of all geriatric psychiatry fellows with the objective of critical evaluation of peer-reviewed, original research articles and learning to apply knowledge to the care of their geriatric patients.

She leads the Geriatric Psychiatry Seminar consisting of weekly developing and implementing basic, core curriculum-focused conference that covers knowledge and skill areas necessary to the successful completion of the geriatric psychiatry training program and commonly seen diagnoses in geriatric psychiatry

She directs the JMH General Psychiatry Residency Training Program and develops and implements comprehensive geriatric specialty lectures in all 4 years of general psychiatric residency training Topics include: normal aging, late-life schizophrenia, late-life depression, ECT, bereavement, neurodegenerative disorders, Alzheimer’s, Vascular, Lewy body disease, neuroimaging and caregiving issues. She also leads the Geriatric Psychiatry Training Program for Jackson Memorial Hospital and the Geriatric Psychiatry Lecture Series.

Community Outreach

This year we continued our community outreach via in-person presentations as well as virtual, reaching Monroe, Miami-Dade, Broward and Palm Beach Counties, as well those who live up north in the warmer months who are able to join via Zoom.

Dr. Galvin gave over 20 educational presentations in the Palm Beach County community addressing over 1,000 people Providing educational talks in our most northern outreach area is serving as an important resource to this aging population

Drs. Magda Tolea and Sarah Getz presented "Lifelong Promoters of Brain Health" as part of a lunch and learn Boynton Beach Library Brown Bag Series

Our EMBI junior faculty continued the “Maintaining a Healthy Aging Brain in a Pandemic World” series in 2022 for the Miami-Dade Public Library System The series continued in a virtual format which allowed the educational talks to reach far beyond the local library that sponsored each event. Over 200 community members were in attendance for these talks. Each presentation was followed by a lengthy question and answer session in which the attendees had the opportunity to speak directly to the doctors. Presentations in the series included:

"How to Sleep to Preserve Brain Health" by Dr. Agudelo

"How Mindfulness Affects the Brain" by Dr. McInerney

"How Nutrition Affects the Brain" by Dr. Marrero

"How Aging Impacts Memory and Cognition" by Dr. Camargo

"Brain Health and Stroke Prevention" by Dr. Marulanda-Londono

"How Sleep Affects the Brain" by Dr. Kaur

Dr. Galvin partnered with the Hussman Institute for Human Genomics (HIHG) to host the Comprehensive Center for Brain Health 2022 Fall Conference. The conference was very well attended.

Junior Faculty from Dr Levin’s Schoninger Neuropsychology Program gave these community presentations

Latino Center on Aging 9th Annual Conference “Una Vida Sin Memoria: Latinos & Alzheimer’s” Parkinson’s Disease in Latinos by Dr Sarno

Living Well with PD: Education Symposium

Invited Panelist for Parkinson’s Association of Southwest Florida, Naples, FL by Dr. Sarno

Virtual Spanish Language Educational Summit Alzheimer’s Foundation of America

Brain Health, Detection, and Diagnosis in the Latino Community by Dr. Buré-Reyes

Parkinson’s Foundation

Hacia Adelante: Navegando el Mar del Parkinson by Drs. Sarno and Buré-Reyes

Center on Aging “Para Mayores” La Poderosa 670 AM Weekly Radio Show

Alzheimer’s Disease and Hispanics: Una Vida Sin Memoria by Dr Sarno

Radio Segment (Spanish) on “Para Mayores” La Poderosa 670 AM

Alzheimer’s Disease: Signs, Symptoms, What to Do & Where to Go for Help by Dr Sarno

iheart Radio Podcast: Estamos Contigo

The Importance of Engagement of Minorities in Research by Dr McInerney

Dr. Crocco gave the following trainings and lectures to the community and to caregivers specifically for the “Alzheimer’s Disease Initiative (ADI) Caregiver Training Seminars in Dementia” in Miami-Dade County. She developed and coordinated four hours of state mandated training to caregivers, ADI respite and daycare professionals and para-professionals for CEU accreditation provided in both English and Spanish. She developed and coordinated four hours of state-mandated dementia training to caregivers in respite and daycare centers for the “ADI Caregiving Training Program in Dementia” in the Florida Keys.

M o s t I m p o r t a n t R e l e v a n t S c i e n t i f i c A c h i e v e m e n t s

Dr. Rundek’s submitting four elaborate and extensive NIH training grants to attempt to recruit the next generation of aging and cognition scientists

Dr. Rundek’s participation in the leadership of the Miami CTSI resubmission and successful renewal of the Miami Center for AIDS Research (CFAR) and Scientific Working Group on Aging and HIV.

Dr. Sun’s initiation and submission of the research grant on the relationship between music and autobiographic memory with the UM Frost School of Music to build a collaboration with aging research and the arts.

Dr. Galvin’s work that focused on applying a precision medicine-like, personalized approach to brain health and the prevention of cognitive decline His group has 28 grants (NIH, Alzheimer's Association, American Academy of Neurology/McKnight) currently totaling $155 Million To make this happen, they have established 56 unique research collaborations with academia, industry and community partners

In 2022 the EMBI stayed within budget. The endowment return revenue was slightly higher than the previous year.

The EMBI completed all programs and supported all researchers and staff as planned.

u r r e n t B u d g e t a n d E n d o w m e n t I n v e s t m e n t R e p o r t

Dr. Rundek, our EMBI Scientific Director has an impressive portfolio of scientific collaborators in our department, institute and university, with other McKnight Brain Institutes as well as across the nation. This graph illustrates the extensive reach of her collaborations

C o n t i n u e d c o l l a b o r a t i o n w i t h o t h e r M c K n i g h t I n s t i t u t e s

NIA U19 Precision Aging Network (PAN) a partnership focused on sustaining healthy minds for life by discovering personalized solutions to improve brain health.

Collaborators: UM - Drs. Rundek, Levin; UA - Drs. Barnes, Ryan

Funding notice for the Florida Consortium to Reduce Misinformation and Exploitation in Alzheimer’s Disease was received in late 2021. It is funded by the Florida DOH Ed and Ethel Moore Alzheimer’s Disease Research Program. Study set-up including IRB approval, commenced this year. The consortium will utilize joint efforts to fight the burgeoning health crisis of misinformation and exploitation in Florida targeting older adults at risk for Alzheimer’s Disease The project builds on research showing parallel disease and fraud vulnerability trajectories rendering older individuals with cognitive impairments, in particular those from underserved racial/ethnic backgrounds, most vulnerable to deception Findings will be used to design interventions in concert with community partners

Collaborators: UM - Dr. Levin; UF - Dr. Ebner; UCF - Dr. Lighthall

W i t h M c K n i g h t I n s t i t u t e s

C O L L A B O R A T I V E P R O G R A M S W I T H M C K N I G H T A N D N O N - M C K N I G H T I N S T I T U T E S

OneFLorida ADRC REC Alzheimer’s Science Training to Advance ResearchSuccess (AlzSTARS) a program to train diverse,multidisciplinary early stage Investigators

Collaborators: UM - Drs. Rundek, Loewenstein; UF - Dr. Smith

Improving Age-Related Cognitive Decline with Exercise in Hypertensive Older Adults: A Pilot Study to Investigate A Retinal Microvascular Biomarker and the Role of IGF-1 MBRF Cognitive Aging and Memory Intervention Core Grant

Collaborators: UM - Drs. Jiang, Wang; UAB - Dr. Lazar

The MBRF Cognitive Aging and Memory Intervention Core awards grants to collaborations among McKnight Brain Institutes on a pilot-study that researches interventions to reduce age-related memory loss and cognitive decline. MBRF Cognitive Aging and Memory Intervention Core Grant Co-Chairs: UM - Dr. Levin; UAB - Dr. Lazar

The UF and UM MBIs collaborated on this research project that was presented at the 2022 Alzheimer's Association International Conference (AAIC) Region specific reduction of neurogranin immunostaining in the hippocampus of Alzheimer’s disease brains

Collaborators: UM - Drs. Vontell, Sun, Davis; UF - Dr. DeKosky

The McKnight Brain Aging Registry (MBAR) study, a collaboration between all four McKnight Institutes has a working group that met regularly in 2022 to review and approve ideas for manuscript submissions Some upcoming proposals are below and the published paper is mentioned on page 20.

“Surviving and Thriving: Evidence for Cortical GABA Stabilization in Cognitively-Intact Oldest-Old Adults” (led by UF)

“Associations Between Exercise Type, Fluid Intelligence, and Processing Speed in the Oldest-old” (led by UF)

“System and Network Segregation relates to Cognition in the Healthy Oldest-Old” (led by UAB)

Dr. Rundek worked with non-McKnight institutes in 2022 on important research collaborations and grant proposals. Here are four new collaborations made this year in which two include the acquisition of new grants and two submissions that are pending review.

Dr. Rundek submitted a grant to NIH with Columbia University (Dr Marco Di Tullio):“Subclinical cardiovascular disease and cognitive function” to evaluate the relationship between cardiovascular abnormalities at an early, subclinical stage and cognitive function, and their possible effects on cognitive decline over time The results of the study may open new horizons in the research on the heart and cognitive function, and possibly indicate new mechanisms of cognitive deterioration that could be targeted for preventive treatment (pending review).

Dr. Rundek submitted a grant with Columbia University (Drs. Moise Desvarieux and Linda Fried) and University of Chicago (Dr. Abibul Ahsan) called PANRECCA, with the overall goal to place the patients and communities impacted by SARS-COV2 at the center of the research in order to improve clinical outcomes and quality of life by 1) advancing understanding and management of post-acute manifestations of SARS-CoV-2 (PASC) in their layered complexity, 2) improving the trajectory these patients endure during their lives, and 3) determining the role of health systems, locality, diversity, socioeconomic factors, timing, and seasonality of infection, viral variants, and vaccination rates in this context (pending review)

This R01 grant (PI: Loewenstein, Co-PI: Rundek) Innovative Deep Phenotyping of African Americans (AAs) at Risk for Alzheimers disease was recently funded The project will deeply phenotype AAs using novel cognitive and biomarker assessments that consider the multiple comorbidities identified in this population The study leverages our vast expertise in neuroimaging and conducting home-based assessment to evaluate clinical and neuropsychological status with equipment that we place within the home

Dr. Rundek in collaboration with UCSD (PI: Dr. Hector Gonzalez; Co-PI: Rundek) just received funding for an NIA R01 titled Study of Latinos-Investigation of Neurocognitive Aging-Alzheimer's disease. The major goals of this project are to study the neurocognitive assessments, MRIs, and PETs among HCHS/SOL participants with cognitive decline and impairment and those meeting MCI and ADRD research criteria.

H o n o r s a n d A w a r d s

On December 12th, at the American Academy of Neurology (AAN) Department Chair Summit, AAN President Orly Avitzur, MD, MBA, announced the renaming of the event to the Ralph L. Sacco Neurology Chair Summit. The naming of the summit in honor of Dr. Sacco, is observation of his relentless commitment to neurology and neurological patients.

Dr. Galvin, Cognitive Division Director, and Director of the Comprehensive Center for Brain Health (CCBH) has been given the Alexandra and Bernard Schoninger Endowed Chair in Memory Disorders There will be a ceremony on January 19, 2023

Ashish Rehni, mentored by Dr Dave, received the Trainee Professional Development Award from the Society for Neuroscience

Nicole Dueker received a Reviewers Choice Abstract for ASHG 2022 which was scored in the top 10% of all abstracts accepted at the annual meeting of American Society of Human Genetics, the largest professional membership organization for specialists in human genetics.

In recognition of his work fostering successful academic careers, Girardin Jean-Louis, Ph.D., director of the Center for Translational Sleep and Circadian Sciences at the University of Miami Miller School of Medicine, has received this year’s Diversity, Equity, and Inclusion Leadership Award from the Associated Professional Sleep Societies, a joint venture of the American Academy of Sleep Medicine (AASM) and the Sleep Research Society

Girardin Jean-Louis, Ph.D., and Kannan Ramar, M.D., president of the Associated Professional Sleep Societies Board of Directors

Three important scientists of our EMBI were celebrated for their leadership and collaborations on International Women’s Day this year. International Women’s Day March 8, 2022

We would like to thank our amazing women leaders who lead with kindness and confidence and create a strong and collaborative team!

Dr. Rundek was elected to the Academy of Science, Engineering and Medicine in Florida (ASEMFL).

N e w G r a n t s f o r E M B I T r a i n e e s

Dr. Agudelo, the McKnight Neurocognitive Scholar was awarded a Diversity Supplement to his mentor’s (Dr Ramos) NIH R01 grant, Sleep in Neurocognitive Aging and Alzheimers Research (SANAR) The overall goal of the parent grant is to test the hypothesis that early and persistent exposure to obstructive sleep apnea increases cognitive decline, mild cognitive impairment, and ADRD Upon the release of funds, this award will support 75% of Dr Agudelo’s effort toward research for two years and provide funds for travel to conferences He was selected for and attended the 2022 Programs to Increase Diversity Among Individuals Engaged in Health Related Research (PRIDE). Dr. Agudelo was specifically selected to attend the Behavioral Medicine and Sleep Disorders Training Institute of PRIDE, which was a 2-week in person career development workshop hosted by the University of Miami Milller School of Medicine in 2022.

Recipients of the Alzheimer’s Association International Research Grants

Four researchers at the University of Miami Miller School of Medicine received Alzheimer’s Association International Research Grants (among them two of our EMBI trainees- Sarah Getz and Michael Kleiman), giving UM the most funded projects of any university in Florida in the organization’s 2022 cycle.

Sarah Getz, PhD, instructor of neuropsychology in the Department of Neurology and Michael Kleiman, PhD, postdoctoral data scientist both mentored by Dr. Galvin, received an Alzheimer’s Association International Research Grant. The International Research Grants program primarily funds early-career scientists working on new ideas in Alzheimer’s research. This effort is part of a comprehensive funding strategy implemented by the Alzheimer’s Association to attract new scientists to the field in an effort to lead future breakthroughs while generating new data and strategies on the disease

Sarah Getz will use her grant funds to research the project Decision Making and Advanced Planning Care in Alzheimer’s Disease She will recruit participants from a pool of 850 adults over 60 with fluid imaging and genetic biomarkers to investigate susceptibility to decision-making problems She plans on using a novel paradigm to measure financial susceptibility and neurocognitive evaluations with the help of her mentor Dr Galvin

Michael Kleiman will use his grant funds for his proposal Mapping Trajectories of Speech Metrics in Preclinical Alzheimer’s Disease. The project aims to detect amyloid, a marker of Alzheimer’s disease, in patients through speech behavior before irreversible damage is done in the brain. Dr. Kleiman uses measured speech behavior using simple picture description or story recall tasks, spectral analysis of audio files, and sentiment analysis using natural language processing to differentiate between people with high and normal amyloid levels Another target of Dr Kleiman’s, involves searching for relationships between speech metrics and other data obtained from the CCBH This includes medical, lifestyle and nutritional data, among others

Michael Kleiman was also awarded the McKnight Clinical Translational Research Scholarship in Cognitive Aging and Age-Related Memory Loss to study his project Assessing Trajectories of Discrete Measures of Speech Behavior in Age-related Decline. The major goal of this project is to investigate the trajectory of speech degradation due to normal age-related cognitive decline using both connected and unconnected speech tasks and natural language processing machine learning algorithms.

Lilah Besser had three grants funded in 2022.

Early Career Investigator Award - Collaborative Cohort of Cohorts for COVID-19 Research (C4R). role: Co-I.

Alzheimer’s Association Research Grant - Neighborhood Segregation and Longitudinal Change in Brain Health Measures. Role: PI.

NIH/NIA R21 - Objectively Measured Neighborhood Greenness in Midlife and Late-life Cognitive and Brain Imaging Outcomes: The Multi-Ethnic Study of Atherosclerosis Role: PI

Dr. Tolea received a Florida DOH Ed and Ethel Moore AD Consortium Grant Optimizing Rural Community Health through Interdisciplinary Detection and Care (ORCHID).

Dr. Vontell was funded to work on three NIH projects this year:

She is an Investigator (PI: Bhattacharya) on an NIH/NIA R01 titled Neuroregeneration in Alzheimer’s Disease.

She is an Investigator (PI: Scott,) on an NIH grant for the NIH NeuroBioBank and Tissue Repository. This will foster the development of a centralized brain and tissue biorepository to supply neurodegenerative, developmental and psychiatric diseased tissue to academic and industry scientists in order to advance biospecimen science and the economic opportunities emerging in the biomedical and biotechnology sectors

She is an Investigator (PI-Scott) for the NIH BRAIN initiative cell atlas network (BICAN)

New Grants for EMBI Faculty

Dr. Rundek received funding for these submissions in 2022

Dr. Rundek’s training grant submission to the Florida DOH Ed and Ethel Moore Alzheimer’s Disease Research Program was funded in the amount of $100,000 00 The training project TRANSlational Fellowship Opportunity for Research on Multimorbidity in Alzheimer’s Disease: TRANSFORM-AD will aim to increase the number of diverse AD/ADRD investigators-leaders in cross-disciplinary clinical translational research, who can effectively and rapidly translate, implement, and disseminate discoveries to practice and community, and to address the special health challenges and health disparities of the diverse AD/ADRD patients we serve through team science and collaborations with community partners and diverse health care stakeholders.

Dr. Rundek’s collaborative T32 training grant study PINNACLE was funded (Role: Co-I). Details on page 31.

Drs. Loewenstein and Rundek (Co-Investigators) received an R01 grant to study Innovative Deep Phenotyping of African Americans (AA) at Risk for Alzheimer's disease. Details on page 51.

The UM CFAR funding was renewed for five years (Role: Senior Investigator and Steering Committee member) Details on page 32

Dr. Rundek as a Co-I received an NIA R01 titled Study of Latinos-Investigation of Neurocognitive Aging-Alzheimer's disease Details on page 46

Dr. Galvin received 4 new NIH awards this year

NIH R01 supplement award to study Retinal Amyloid Imaging with our EMBI collaborators Drs. Jiang & Wang. The major goals of this project are to develop, validate and test retinal amyloid imaging using confocal scanning laser ophthalmoscopy and optical coherence tomography in a longitudinal study of ADRD biomarkers in a deeply phenotyped multicultural sample of older adults. Role: PI

NIH/NIA R01to research A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients with Mild-to-Moderate Dementia with Lewy Bodies. The major goal of this project is to conduct a Phase 2b clinical trial of Neflamapimod, a novel disease-modifying compound, in patients with mild to moderate dementia with Lewy bodies. Role: MPI.

NIH/NIA RF1 Alzheimer’s Disease and Related Dementias (ADRD) Prevalence in American Samoa. The major goals of this project are to assess ADRD health literacy and research readiness, establish the prevalence of mild cognitive impairment and ADRD, and study genetic and plasma ADRD biomarkers Role: MPI

NIH/NIA R56 Deep Phenotypic Characterization of Prodromal Dementia with Lewy Bodies The major goal of this study is to model prodromal DLB using deep phenotyping and describe the risk of conversion to clinical symptomatic stages of disease in order to increase accurate and early diagnosis, develop therapeutic targets, and improve health outcomes in DLB Role: PI

Dr. Sun received an award as a Co-Investigator to study the Neural Network Connectivity of Autobiographical Music in Adults with Mild Cognitive Impairment and Mild Alzheimer’s Disease from the Lee Peach Foundation This is the basis of her newest partnership with the UM Frost School of Music

Dr. Davis was awarded the following grants in 2022.

Herbert W. Hoover Foundation: Detecting Nanoplastics in the Olfactory Pathway: A Feasibility Study Role: PI

NIH NINDS - Single-nucleus Transcriptome Profiling Across Multiple Brain Regions in Parkinson's Disease Role: Co-I

U S Department of Veterans Affairs - The National Posttraumatic Stress Disorder Biorepository Brain Role: Co-I

NIH NINDS - The NIH Brain and Tissue Repository Role: Co-I

Dr. McIntosh received a Center for AIDS Research (CFAR) Small Pilot Program grant to study Geriatric Resilience Informed by Precision Selection (GRIPS) Role: PI; Co-Investigator: Dr. Levin

Dr. Bracko received three grant awards this year:

One was an R21 from the NIH for Investigating the cause of cerebral blood flow reductions in a mouse model of frontotemporal dementia.

Another was an AARG grant from the Alzheimer’s Association to research Single-cell analysis of neutrophil subpopulations and their contribution to vascular inflammation in mouse models of Alzheimer’s disease

The third was a Provost's Research Award for the role of neutrophils in microvascular dysfunction in mouse models of Alzheimer’s disease

Name (in alphabetical

FACULTY (LEADERSHIP & MEMBERS)

Institute Role Area of Expertise

Radiology, Physics (MRI)

Neurobiology, Basic Science

Neuro-opthalmology,

Neuropsychology

order)

Noam Alperin, PhD Neuroimaging Core Director

Christian Camargo, MD Member Neurology

Kunjan R Dave, PhD Member

David Della-Morte, MD, PhD Member Neurology

Joyce Gomes-Osman, PT, PhD Member Physical Therapy, Neurology

Hong Jiang, MD, PhD Member

Neurology

Bonnie Levin, PhD Cognitive Core Director & Scientific Advisory Board

Miguel Perez-Pinzon, PhD Member & Scientific Advisory Board Neuroscience

Tatjana Rundek, MD, PhD Scientific Director & Scientific Advisory Board Neurology, Epidemiology

Ralph L. Sacco, MD, MS Executive Director & Scientific Advisory Board Neurology, Epidemiology, Genetics

Xiaoyan Sun, MD, PhD Educational Director & Scientific Advisory Board Neuroscience, Biochemistry

FACULTY (COLLABORATORS)

Name

(in alphabetical order) Institute Role Area of Expertise

Lilah Besser, PhD, MSPH

Collaborator

Neurology

Susan Blanton, PhD Collaborator Genetics

Oliver Bracko, PhD Collaborator Neuroscience

Scott Brown, PhD Collaborator Public Health

Elizabeth Crocco, MD Collaborator Psychiatry

Chuanhui Dong, PhD

James Galvin, MD, MPH

Collaborator

Epidemiology, Biostatistics

Collaborator & Scientific Advisory Board Neurology

Sarah Getz, PhD Collaborator

Neuropsychology

Ihtsham Haq, MD

Collaborator

Neurology

Girard Jean-Louis, PhD

Collaborator

Psychiatry, Neurology

FACULTY (COLLABORATORS CONT.)

Name (in alphabetical order) Institute Role Area of Expertise

David

Loewenstein PhD Collaborator & Scientific Advisory Board

Michelle Marrero, MD Collaborator

Katalina McInerney, PhD Collaborator

Roger McIntosh, PhD Collaborator

Milena Pinto, PhD Collaborator

Alberto Ramos, MD

Collaborator

Neuropsychology

Neurology

Neuropsychology

Psychology

Neuroscience

Neurology, Sleep Medicine

Ami Raval, PhD

Collaborator

Neuroscience, Epidemiology

Magdalena Tolea, PhD Collaborator Neurology

Regina Vontell, PhD, MA Collaborator Neurology

Jianhua Wang, MD, PhD Collaborator

Neuro-ophthalmology, Neurology

Name (in alphabetical order) Institute

TRAINEES

Role

Area of Expertise

Christian Agudelo, MD McKnight Cognitive Scholar Neurology

Mentor

Tatjana Rundek, MD, PhD Xiaoyan Sun, MD, PhD Alberto Ramos, MD

Abdulrahman Allaf MD Student Neuro-ophthalmology Hong Jiang, MD, PhD Jinhua Wang, MD, PhD

Botagoz Aimagambetova, MD Post-Doctoral Fellow

Neurology Tatjana Rundek, MD, PhD

Ayham Alkhachroum, MD Assistant Professor Neurology Tatjana Rundek, MD, PhD

Taylor Ariko, BS PhD Student Biomedical Engineering Tatjana Rundek, MD, PhD

Nikhil S. Banerjee, PhD Post-Doctoral Fellow Neuropsychology Bonnie Levin, PhD

Zoe Bassett Undergrad Trainee Neuroscience Ami Raval, PhD

Sharvan Chabria, BS Practicum Student Neuropsychology Bonnie Levin, PhD

Supriya Chakraborty PhD Student Biology Oliver Bracko, PhD Kaitlyn Chang Graduate Trainee Neuroscience Ami Raval, PhD

Jack Cipolla MD Student Neurology

Hong Jiang, MD, PhD Jinhua Wang, MD, PhD

Estefany Saez Clark, MA Practicum Student Neuropsychology Bonnie Levin, PhD

Ileana Pacheco-Colon Post-Doctoral Fellow Neuropsychology Bonnie Levin, PhD

E. Valerie Daniel, PhD Post-Doctoral Fellow Public Health James Galvin, MD, MPH

Katie Dillon, MA Graduate Trainee Neuroscience, Psychology Roger McIntosh, PhD

Alexander Douma Undergrad Student Neuroscience

Ami Raval, PhD

Emma Ducca, PhD Post-Doctoral Fellow Neuropsychology Bonnie Levin, PhD

Iris Escobar PhD Student Neurology Miguel Perez-Pinzon, PhD

Eric Fagerli PhD Student Neuroscience Miguel Perez-Pinzon, PhD

Alferado Fernandoez Undergrad Student Neuroscience

Elizabeth Gabrielli, MD Post-Doctoral Fellow

Anesthesiology

Ami Raval, PhD

Alberto Ramos, MD

Name (in alphabetical order)

Institute Role Area of Expertise

Nakisa Ghannad, MS Practicum Student

Mentor

Neuropsychology Bonnie Levin, PhD

Ryan Gober, BS PhD Candidate Neuroscience Regina Vontell, PhD

Eugenia Victoria Gomez Undergraduate Student Neuroscience Milena Pinto, PhD

Christian Gonzalez, PhD Post-Doctoral Fellow Neuropsychology David Loewenstein, PhD

Zachary Goodman Practicum Student Neuropsychology Bonnie Levin, PhD

Emmanuel Gorrin Graduate Trainee Neuroscience Ami Raval, PhD

Scott Harcourt Post-Doctoral Fellow Neuropsychology Bonnie Levin, PhD

Diana Hipcample, PhD Post-Doctoral Fellow Neuropsychology David Loewenstein, PhD

Kia Howard, BS Pre-Doctoral Trainee Neuroscience Roger McIntosh, PhD

Charlie Jackson Graduate Student Neuroscience Miguel Perez-Pinzon, PhD

Karlon Johnson, PhD Pre-Doctoral Trainee Public Health Tatjana Rundek, MD, PhD

Nathan Johnson PhD Candidate Neurology Xiaoyan Sun, MD, PhD

Sonya Kaur, PhD Instructor Neuropsychology

Bonnie Levin, PhD Tatjana Rundek, MD, PhD Alberto Ramos, MD

Michael Kleiman, PhD Data Scientist Experimental Psychology James Galvin, MD, MPH

Kayla Kotalik, BS Practicum Student Neuropsychology Bonnie Levin, PhD

Nastajjia Krementz, MD Stroke-Net Fellow Neurology, Stroke Ralph Sacco, MD, MS

Eduaro Leal, PhD Post-Doctoral Fellow Neuropsychology David Loewenstein, PhD

Che Liu Graduate Student Neuroradiology Noam Alperin, PhD

Rosario Pintos Lobo Practicum Student Neuropsychology Bonnie Levin, PhD

Berk Mankaliye Undergrad Trainee Neuroscience Ami Raval, PhD

Jacquelyn Moffit, MA Practicum Student

Neuropsychology Bonnie Levin, PhD

Emily Cecilia Morales Graduate Student Biochemistry Ami Raval, PhD

Name (in alphabetical order)

Institute Role Area of Expertise

Mentor

Amanda Neves Post-Doctoral Trainee Basic Science Neurology Milena Pinto, PhD

Stephanie Novotny, MS Pre-Doctoral Trainee Neuropsychology Bonnie Levin, PhD

Alexandra Ortega Post-Doctoral Fellow Neuropsychology David Loewenstein, PhD

Deirdre O’Shea Post-Doctoral Fellow Neurology James Galvin, MD, MPH

Nidhi H Patel, MD Graduate Trainee Neurology, Stroke Ralph Sacco, MD, MS

Sonya Patel Undergrad Student Neuroscience

Ami Raval, PhD

Gina Perez Undergrad Student Neuroscience Ami Raval, PhD

Jahanett Ramirez, MD, MPH Post-Doctoral Trainee Neurology Alberto Ramos, MD

Varun Reddy Student Neuroscience

Ami Raval, PhD Ashish Rehni, PhD Post-Doctoral Fellow Neuroscience Kunjan Dave, PhD Dayana Rodriguez Post-Doctoral Fellow Neuropsychology Bonnie Levin, PhD

Anita Seixas Dias Saporta, MD McKnight Fellow Neurology, Imaging

Tatjana Rundek, MD, PhD Ralph Sacco, MD, MS

Ratanpriya Sharma, MA Graduate Trainee Neuroscience, Psychology Roger McIntosh, PhD

Hossein Shayestehyekta, MD Post-Doctoral Trainee Neurology

Jonathan Siegel Graduate Student Biochemistry

Ava Simms, MD Post-Doctoral Trainee Neurology

Christina Stutts Graduate Student Music Therapy

Hong Jiang, MD, PhD Jinhua Wang, MD, PhD

Ami Raval, PhD

Hong Jiang, MD, PhD Jinhua Wang, MD, PhD

Xiaoyan Sun, MD, PhD

Nicole B Sur, MD Assistant Professor Neurology, Stroke Tatjana Rundek, MD, PhD

Thomas Tsai, MS Practicum Student Neuropsychology Bonnie Levin, PhD

Sebastian Vargas-George

Undergrad Trainee

Neuroscience

Ami Raval, PhD

Chiara Villa Post-Doctoral Trainee Neurology Milena Pinto, PhD

Megan Wurtz Undergrad Trainee Neuroscience

Ami Raval, PhD

A P P E N D I X 2

Rundek T, Del Brutto VJ, Goryawala M, Dong C, Agudelo C, Saporta AS, Merritt S, Camargo C, Ariko T, Loewenstein DA, Duara R, Haq I Associations Between Vascular Risk Factors and Perivascular Spaces in Adults with Intact Cognition, Mild Cognitive Impairment, and Dementia. J Alzheimers Dis. 2022;89(2):437-448.

Rundek T, Tolea M, Ariko T, Fagerli EA, Camargo CJ. Vascular Cognitive Impairment (VCI). Neurotherapeutics. 2022 Jan;19(1):68-88.

Iadecola C, Fisher M, Sacco RL. Introduction to the Compendium on Stroke and Neurocognitive Impairment. Circ Res. 2022 Apr 15;130(8):1073-1074.

Mishra A, Malik R, Hachiya T, Jürgenson T, Namba S, Posner DC, Kamanu FK, Koido M, Le Grand Q, Shi M, et al Stroke genetics informs drug discovery and risk prediction across ancestries Nature. 2022;611(7934):115-123

*Drs. Sacco and Rundek were involved in this large international publication

Feigin VL, Brainin M, Norrving B, Martins S, Sacco RL, Hacke W, Fisher M, Pandian J, Lindsay P World Stroke Organization (WSO): Global Stroke Fact Sheet 2022 Int J Stroke 2022 Jan;17(1):18-29 doi: 10.1177/17474930211065917. Erratum in: Int J Stroke. 2022 Apr;17(4):478.

Beaman C, Kozii K, Hilal S, Liu M, Spagnolo-Allende AJ, Polanco-Serra G, Chen C, Cheng CY, Zambrano D, Arikan B, Del Brutto VJ, Wright C, Flowers XE, Leskinen SP, Rundek T, Mitchell A, Vonsattel JP, Cortes E, Teich AF, Sacco RL, Elkind MSV, Roh D, Gutierrez J; Alzheimer's Disease Neuroimaging Initiative. Cerebral Microbleeds, Cerebral Amyloid Angiopathy, and Their Relationships to Quantitative Markers of Neurodegeneration. Neurology. 2022 Apr 19;98(16).

Hinchman CA, Cabral DF, Ciesla M, Flothmann M, Nunez C, Rice J, Loewenstein DA, Kitaigorodsky M, Cahalin LP, Rundek T, Pascual-Leone A, Cattaneo G, Gomes-Osman J Exercise engagement drives changes in cognition and cardiorespiratory fitness after 8 weeks of aerobic training in sedentary aging adults at risk of cognitive decline Front Rehabil Sci 2022 Aug 2;3:923141

Deng Y, Wang H, Simms AG, Hu H, Zhang J, Gameiro GR, Rundek T, Signorile JF, Levin BE, Yuan J, Wang J, Jiang H Age-related focal thinning of the ganglion cell-inner plexiform layer in a healthy population Quant Imaging Med Surg 2022 Jun;12(6):3034-3048

Adjoian Mezzaca T, Dodds LV, Rundek T, Al Hazzouri Z, Caunca MR, Gomes-Osman J, Loewenstein DA, Schneiderman N, Elfassy T. Associations Between Cognitive Functioning and Mortality in a Population-Based Sample of Older United States Adults: Differences by Sex and Education. Journal of Aging and Health 2022 Oct;34(6-8):905-915

Ali M, Falkenhain K, Njiru BN, Murtaza-Ali M, Ruiz-Uribe NE, Haft-Javaherian M, Catchers S, Nishimura N, Schaffer CB, Bracko O VEGF signalling causes stalls in brain capillaries and reduces cerebral blood flow in Alzheimer's mice Brain 2022 May 24;145(4):1449-1463

McIntosh RC, Lobo J, Paparozzi J, Goodman Z, Kornfeld S, Nomi J Neutrophil to lymphocyte ratio is a transdiagnostic biomarker of depression and structural and functional brain alterations in older adults. J Neuroimmunol. 2022 Apr 15;365:577831.

Brody M, Agronin M, Herskowitz BJ, Bookheimer SY, Small GW, Hitchinson B, Ramdas K, Wishard T, McInerney KF, Vellas B, Sierra F, Jiang Z, Mcclain-Moss L, Perez C, Fuquay A, Rodriguez S, Hare JM, Oliva AA Jr, Baumel B. Results and insights from a phase I clinical trial of Lomecel-B for Alzheimer's disease. Alzheimers Dement. 2022. Epub ahead of print.

Rafati AH, Ardalan M, Vontell RT, Mallard C, Wegener G. Geometrical modelling of neuronal clustering and development Heliyon 2022 Jul 8;8(7)

Loewenstein DA, Curiel Cid RE, Kitaigorodsky M, Ortega A, Hincapie D, Zheng DD, Amaya A, Gallardo L, Manso L, Sosa J, Crocco EA Persistent Failure to Recover from Proactive Semantic Interference on the Cognitive Stress Test Differentiates Between Amnestic Mild Cognitive Impairment, Pre-Mild Cognitive Impairment, and Cognitively Unimpaired Older Adults J Alzheimers Dis 2022;90(1):313322

Joshi MS, Galvin JE Cognitive Resilience in Brain Health and Dementia Research J Alzheimers Dis 2022;90(2):461-473.

Mirabnahrazam G, Ma D, Beaulac C, Lee S, Popuri K, Lee H, Cao J, Wang L, Galvin JE, Beg MF. Predicting Alzheimer's disease progression in healthy and MCI subjects using multi-modal deep learning approach. Alzheimers Dement. 2022 Dec;18 Suppl 2:e060949.

Liu C, Lee SH, Loewenstein DA, Galvin JE, Camargo CJ, Alperin N. Poor sleep accelerates hippocampal and posterior cingulate volume loss in cognitively normal healthy older adults. J Sleep Res 2022 Aug;31(4):e13538

Garcia S, Saldana-Caboverde A, Anwar M, Raval AP, Nissanka N, Pinto M, Moraes CT, Diaz F Enhanced glycolysis and GSK3 inactivation promote brain metabolic adaptations following neuronal mitochondrial stress Hum Mol Genet 2022 Mar 3;31(5):692-704

Nolin SA, Cowart H, Merritt S, McInerney K, Bharadwaj PK, Franchetti MK, Raichlen DA, Jessup CJ, Hishaw GA, Van Etten EJ, Trouard TP, Geldmacher DS, Wadley VG, Porges ES, Woods AJ, Cohen RA, Levin BE, Rundek T, Alexander GE, Visscher KM. Validity of the NIH toolbox cognitive battery in a healthy oldest-old 85+ sample. J Int Neuropsychol Soc 2022:1-10.

Publications by Trainees as Lead Authors

Goodman ZT, Banerjee N, Rooks J, McInerney K, Sun X, Getz S, Kaur S, Sun-Suslow N, Junco B, Levin BE Measuring the Frailty Phenotype and its Association with Cognition in Mid-Life and Older Age J Alzheimers Dis 2022;89(2):415-426

Daniel EV, Kleiman MJ, Galvin JE. Exploring Reasons for Differential Vulnerability and Alzheimer's Disease Risk in Racial and Ethnic Minorities J Alzheimers Dis 2022 Nov 24

Kleiman MJ, Ariko T, Galvin JE; Alzheimer’s Disease Neuroimaging Initiative. Hierarchical Two-Stage Cost-Sensitive Clinical Decision Support System for Screening Prodromal Alzheimer's Disease and Related Dementias. J Alzheimers Dis. 2022 Dec 7.

Kleiman MJ, Plewes AD, Owora A, Burkhardt AS, Grout RW, Dexter PR, Fowler N, Galvin JE, Ben Miled Z, Boustani M. Digital detection of dementia (D3): A pragmatic cluster-randomized trial examining the application of patient-reported outcomes. Trials, 23:868, 2022.

Besser LM, Meyer OL, Jones MR, Tran D, Booker M, Mitsova D, Peterson R, Galvin JE, Bateman JR, Hayden KM, Hughes TM Neighborhood segregation and cognitive change: Multi-Ethnic Study of Atherosclerosis Alzheimers Dement 2022 Jul 23

Besser LM, Mitsova D, Williams CL, Wiese L Redlining and Neighborhood Walking in Older Adults: The 2017 National Household Travel Survey Am J Prev Med 2022 Dec;63(6):926-934

Besser LM, Bean C, Foor A, Hoermann S, Renne J Evaluating Racial/Ethnic Equity in PlanningRelated U.S. Health Impact Assessments Involving Parks and Greenspaces, Journal of the American Planning Association 2022, DOI: 10.1080/01944363.2022.2096100.

Besser LM, Galvin JE. Rural Versus Non-Rural Residence and Psychosocial Outcomes Among Caregivers of Patients with Dementia and Related Disorders. J Alzheimers Dis. 2022;85(3):993-999.

Dueker ND, Wang L, Gardener H, Gomez L, Kaur S, Beecham A, Blanton SH, Dong C, Gutierrez J, Cheung Y-K, Moon Y, Levin B, Wright CB, Elkind M, Sacco RL, Rundek T. Genome-Wide Association Study of Executive Function in a Multi-Ethnic Cohort Implicates LINC01362: Results From the Northern Manhattan Study Neurobiology of Aging Online, ahead of Print December 5, 2022

Reddy V, McCarthy M, Raval AP. Xenoestrogens impact brain estrogen receptor signaling during the female lifespan: A precursor to neurological disease? Neurobiol Dis. 2022 Feb;163:105596.

Silva NCBS, Bracko O, Nelson AR, de Oliveira FF, Robison LS, Shaaban CE, Hainsworth AH, Price BR Vascular cognitive impairment and dementia: An early career researcher perspective Alzheimers Dement (Amst) 2022 Apr 27;14(1):e12310

Alkhachroum A, Bustillo AJ, Asdaghi N, Ying H, Marulanda-Londono E, Gutierrez CM, Samano D, Sobczak E, Foster D, Kottapally M, Merenda A, Koch S, Romano JG, O'Phelan K, Claassen J, Sacco RL, Rundek T Association of Acute Alteration of Consciousness in Patients With Acute Ischemic Stroke With Outcomes and Early Withdrawal of Care Neurology 2022;10

Book Chapters

Rundek T. Neurovascular ultrasound (Chapter 24). In: Merritt’s Neurology, 14th Edition, Louis ED, Mayer SA, Rowland JP (Eds); Wolters Kluwer, 2022; 208-216.

Rundek T, Yang D, Simonetto ML, Campo N, Cabral D Intracerebral Venous System: Monitoring by Transcranial Color Coded Duplex Sonography (Chapter 28) In: Neurosonology in Critical Care Rodriguez, Baracchini (Eds); Springer Nature Switzerland AG 2022; 483-494

Del Brutto V, Rundek T, Sacco RL Prognosis after stroke (Chapter 17) In: Stroke- Pathophysiology, Diagnosis, and Management Mohr JP, Grotta, Alberts GW, Broderick JP, Asner SE, Lo EH, Mendelow D, Sacco RL, Wong LKS (Eds); Seventh edition, Elsevier Inc , 2022; 207-220

Espinel Z, Crocco EA, Dementia. In: Taking Care of You: The Empowered Woman’s Guide to Better Health, MI O’Connell, KL Haq. (Eds); Mayo Clinic Press: Rochester, MN, 2022.

Srshadri S, Caunca M, Rundek T. Vascular Dementia and Cognitive Impairment (Chapter 18). In: Stroke- Pathophysiology, Diagnosis, and Management. Mohr JP, Grotta, Alberts GW, Broderick JP, Asner SE, Lo EH, Mendelow D, Sacco RL, Wong LKS (Eds); Seventh edition, Elsevier Inc., 2022; 221236.

Semple PF, Sacco RL An Atlas of Stroke (The Encyclopedia of Visual Medicine Series) London Espinel Z, Crocco EA, Mental status in the moment In: Geriatric Psychiatry (What Do I Do Now Psychiatry), ME Agronin, IV Vahia (Eds); Oxford University Press: NY, Chapter 3, 2022

Rueda-Lara M, Crocco EA, I’m always afraid In: Geriatric Psychiatry (What Do I Do Now Psychiatry), ME Agronin, IV Vahia, (Eds); Oxford University Press: NY, Chapter 13, 2022

Luca L, Crocco EA, It’s just a nightcap In: Geriatric Psychiatry (What Do I Do Now Psychiatry), ME Agronin, IV Vahia, (Eds); Oxford University Press: NY, Chapter 28, 2022.

A P P E N D I X 3

M E E T I N G S

This year’s Alzheimer’s Association International Conference took place in San Diego and five EMBI TRAINEES from our EMBI presented their work. Three of the presenters are trainees being mentored by our EMBI cognition scientists and one presentation was a collaborative effort with the UF MBI.

AAIC Presentations Given by our EMBI Trainees

Taylor Ariko, Hannah Gardener, Bonnie Levin, Xiaoyan Sun, Stacy Merritt, Weizhao Zhao, Consuelo Mora-McLaughin, Jose Gutierrez, Mitchell S.V. Elkind, Ralph Sacco, Noam Alperin, Tatjana Rundek. Impacts of Cerebral Small Vessel Disease on Global and Domain-Specific Cognition. AAIC 2022. Poster Presentation, PRESENTER.

Lilah Besser, Marcia Pescador Jimenez, Oanh L. Meyer, Kristen M. George, Paris AJ Adkins-Jackson, Diana Mitsova, James E. Galvin. Neighborhood Greenspace as a Social Determinant of Health and How Associations with Brain Health Outcomes May Differ by Race/Ethnicity. AAIC 2022. Poster Presentation, PRESENTER

Julian Dallmeier, Regina Vontell, David Davis, Ryan Gober, Ayled Barreda, Xiaoyan Sun, Connor Wander, Todd Cohen, William K Scott Correlation of Corporaamylacea and pTau in Postmortem Hippocampal Human Brain Tissue AAIC 2022 Poster Presentation, PRESENTER

P R E S E N T A T I O N S A T S C I E N T I F I C O R P U B L I C

E. Valerie Daniel, Lisa Ann Kirk Wiese, James Galvin. Cognitive Screening among Older AfroCaribbean Adults in Rural Areas of South Florida. AAIC 2022. Poster Presentation, PRESENTER.

Michael Kleiman, Two-stage Cost-sensitive Clinical Decision Support System for Detecting Alzheimer's Disease. AAIC 2022. Poster Presentation, PRESENTER.

Regina T. Vontell, David A Davis, Julian Dallmeier, Ayled Barreda, Kaj Blennow, Henrik Zetterberg, Hlin Kvartsberg, Sakir Humayun Gultekin, Steven T DeKosky, Tatjana Rundek, William K Scott, Xiaoyan Sun Region Specific Reduction of Neurogranin immunostaining in the Hippocampus of Alzheimer’s Disease Brains *This is a multi-MBI collaboration with Dr DeKosky from the University of Florida MBI AAIC 2022 Poster Presentation, PRESENTER

AAIC Presentations Involving EMBI Cognitive Clinicians and Scientists

Tatjana Rundek, Victor Del Brutto, Mohammed Goryawala, Anita Seixas Dias Saporta, Stacy S Merritt, Christian Camargo, Christian Agudelo, Taylor Ariko, Chuanhui Dong, , Ranjan Duara, Ihtsham U Haq Determinants of enlarged perivascular spaces (ePVS) on MRI: The Florida Vascular Imaging Phenotypes (FL-VIP) Study of AD risk. AAIC 2022. Poster Presentation.

Christian Camargo, Katalina McInerney, Stacy S. Merritt, Marisa Modjeski, Danielle Counotte, Tatjana Rundek. Reducing the Effects of Aging on Cognition with Therapeutic Intervention of an Oral multiNutrient combination (REACTION): Study Design and Baseline Results. AAIC 2022. Poster Presentation.

Elizabeth Mahanna-Gabrielli, Sayaka Kuwayama, Wassim Tarraf, Delia Cabrera DeBuc, Jianwen Cai, Martha L Daviglus, Charlotte Joslin, David J Lee, Carlos Mendoza-Santiesteban, Ariana M Stickel, Diane Zheng, Hector M González, Alberto Ramos Sleep, self-reported ocular health, and cognition in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation of Neurocognitive Aging (SOL-INCA) AAIC 2022 Poster Presentation

Delia Cabrera DeBuc, Alberto R. Ramos, Anat Galor, Rishav Sapahia, Ardita Hasalami, Javier De Jesus Fernandez, Ranya Habash Kernel Flow and the Eye- Brain Connectome: Towards a more robust technique to identify high-risk individuals before cognitive decline AAIC 2022 Poster Presentation

Hong Jiang, Ava Gaye Yanique Simms, Bernard Baumel, Tatjana Rundek, Jinhua Wang. Impaired retinal capillary function in patients with clinical Alzheimer’s disease. AAIC 2022. Poster Presentation.

James Galvin chaired the “Neuropsychology: Measurement and markers of AD and non-AD dementias” session.

James Galvin. The Brain Health Platform: Combining Resilience, Vulnerability and Performance to Assess Brain Health and Risk of Alzheimer’s Disease and Related Disorders. AAIC 2022. Presentation.

James Galvin, Michael J Kleiman, Lun-Ching Chang The Brain Health Platform: Combining Resilience, Vulnerability and Performance to assess brain health and risk of Alzheimer’s disease and related disorders AAIC 2022

Da Ma, Cédric Beaulac, Sieun Lee, Karteek Popuri, Hyunwoo Lee, Jiguo Cao, Lei Wang, James E. Galvin, Mirza Faisal Beg Predicting Alzheimer’s disease progression in healthy and MCI subjects using multi-modal deep learning approach AAIC 2022 Poster Presentation

Naomi S. Chaytor, Elson S. Floyd, Yunusa M Olufadi, Dedra Buchwald, James E. Galvin, Maureen Schmitter-Edgecombe, Asrid M Suchy-Dicey. Intraindividual variability of cognitive performance and associations with magnetic resonance imaging in aging American Indians: Data from the Strong Heart Study. AAIC 2022. Poster Presentation.

Ghazal Mirabnahrazam, Da Ma, Cédric Beaulac, Sieun Lee, Karteek Popuri, Hyunwoo Lee, Jiguo Cao, Lei Wang, James E Galvin, Mirza Faisal Beg. Predicting Alzheimer’s Disease Progression in Healthy and MCI Subjects Using Multi-modal Deep Learning Approach. AAIC 2022. Poster Presentation.

Dr. Bracko organized the workshop Microvascular dysfunction in VCID: From bench to bedside AAIC 2022

Gober R, Davis D, Barreda A, Duque L, Garamszegi SP, Sun X, Scott WK, Vontell R Inflammasome assembly as a potential mechanism of microglial activation and neuroinflammation in schizophrenia Society for Neuroscience Annual Meeting 2022 San Diego, CA

Dallmeier J, Vontell R, Davis D, Gober R, Barreda A, Sun X, Wander C, Cohen T, Scott WK Regional population differences of Corpora amylacea in postmortem hippocampal human brain tissue. Society for Neuroscience Annual Meeting 2022. San Diego, CA.

Ashish K. Rehni, Sunjoo Cho, Kunjan R. Dave. Insulin-treated diabetic rats exhibit enhanced stroke risk for at least 7 days post-recurrent hypoglycemia exposure. Society for Neuroscience Annual Meeting 2022. San Diego, CA.

Sunjoo Cho, Ashish K. Rehni, Kunjan R. Dave. Chronic nicotine exposure increases blood-brain barrier permeability by decreasing tight junction protein levels and increases inflammation in aged male rats Society for Neuroscience Annual Meeting 2022 San Diego, CA

Oliver Bracko. The role of neutrophils in brain blood flow reductions in Alzheimer’s. Speaker at Mini Symposium at the Society for Neuroscience Annual Meeting 2022. San Diego, CA.

Oliver Bracko was Chair for the “Microvessel, Big Problem?: A Brain Journey From Health to Disease” session Symposium at the Society for Neuroscience Annual Meeting 2022 San Diego, CA

Milena Pinto Human Nmnat1 promotes autophagic clearance of amyloid plaques in a model of Alzheimer’s Disease Society for Neuroscience Annual Meeting 2022 San Diego, CA

Nathan d’Adesky, Shahil H Patel, Nicole Manelis and Ami P. Raval Sex difference in the cerebral metabolism of amino acid in rats after electronic cigarette derived nicotine exposure Society for Neuroscience Annual Meeting 2022. San Diego, CA.

Hari Pradhyumnan, Berk Mankaliye, Shahil H. Patel, Helen Bramlett and Ami P. Raval Effects of electronic cigarette vaping on histamine metabolism in rats of both sexes. Society for Neuroscience Annual Meeting 2022. San Diego, CA.

Shahil H. Patel, Isabel Saul, Kunjan R. Dave, Miguel A. Perez-Pinzon and Ami P. Raval. Nicotine withdrawal and stroke outcome in female rats. Society for Neuroscience Annual Meeting 2022. San Diego, CA

Akgun B, Rajabli F, Adams L, Starks T, Laux R, Whitehead-Gay P, Kunkle B, Caban-Holt A, McInerney K, Cuccaro M, Vance J, Haines J, Smith Byrd G, Beecham G, Pericak-Vance M, & Seixas A The relationship of Alzheimer disease, genetic risk, and education in individuals of African Ancestry Annual Meeting of the American Society of Human Genetics October 2022 Los Angeles, CA

Nicole Dueker Epigenetic Age Acceleration is Suggestively Associated with Stroke Precursor Phenotypes American Society of Human Genetics Poster session and Poster talk at ASHG 2022 in Los Angeles

M. Muniz Moreno, K. Celis, F. RAJABLI, P. Whitehead, K. Hamilton-Nelson, G. Beecham, D. Dykxhoorn, K. Nuytemans, L. Wang, O.Gardner, D. Dorfsman, E. Bigio, M. Mesulam, D. Bennett, T. Schuckt, S. Weintraub, C. Geula, M. Gearin, C. Alba, C. Dalgard, D. Davis, W. Scott, J. L. Haines, M. Pericak-Vance, A. Griswold2, J. Young, J. Vance. Increased mitochondrial expression is associated with increased APOE e4 expression and affected by ancestry and sex. Annual Meeting of the American Society of Human Genetics. October 2022. Los Angeles, CA.

Two junior faculty in Dr. Galvin’s Comprehensive Center for Brain Health (CCBH) presented at the Gerontological Society of America.

Magdalena Tolea, Iris Cohen, James Galvin Mindfulness and Caregiving Experience in ADRD Gerontological Society of America Annual Scientific Meeting, Nov 2022

Lilah Besser Cognition in Context: Investigating the Role of Built, Social, and Natural Environments in Cognitive Aging. Gerontological Society of America Annual Scientific Meeting, Nov 2022.

Garamszegi SP, Banack SA, Cox PA, Bradley WA, Brand LE, Tischbein M, Stommel EJ, and Davis DA. Detection of the Cyanobacterial Toxin BMAA in the Olfactory Pathway of Postmortem Human Brains. 2022 Society of Toxicology Annual Meeting San Diego, CA.

Our Basic and Translational Science Researchers gave several important presentations in 2022.

Ashish K Rehni, Allen Liu, Sunjoo Cho, Kunjan R. Dave Insulin-treated diabetic rats demonstrate increased stroke risk when exposed to recurrent hypoglycemia Brain & Pet 2022 (Glasgow)

Sunjoo Cho, Ashish K. Rehni, Kunjan R. Dave TNF-α inhibition attenuates nicotine-induced BBB impairment and hematoma expansion in collagenase-induced ICH in rats. Brain & Pet 2022 (Glasgow).

Ashish K. Rehni, Sunjoo Cho, Ami P. Raval, Miguel A. Perez-Pinzon, Wenche Jy, Kunjan R. Dave. The therapeutic window of red cell microparticles in limiting intracerebral hemorrhage-induced hematoma growth in nicotine-exposed rats. International Stroke Conference 2022.

Kerr N, Sanchez J, Moreno WJ, Furones-Alonso OE, Dietrich WD, Bramlett HB and Raval AP. Irisin, elicited by low frequency whole body vibration or exogenously, improves post-stroke cognition and reduces infarct volume in middle-aged rats International Stroke Conference March 2022-Held Inperson and Virtual at New Orleans February 8-11 2022 (Refereed)

Drs. Jiang and Wang’s work was presented at the three important conferences this year.

Association for Research in Vision and Ophthalmology Conference.

Wang, Simms, Sadaghiani, Jiang, Morgan, Aguirre, Pattany, Detre, Jiang. Multi-center repeatability of macular capillary perfusion density using optical coherence tomography angiography. ARVO 2022 conference poster presentation

North American Neuro Ophthalmology Society Conference

Jiang, Signorile, Wang Improvement of retinal capillary function after high-speed circuit resistance training in healthy older adults. NANOS 2022 conference, featured poster.

American Academy of Ophthalmology Conference

Jiang, Signorile, Wang Improvement of retinal capillary function after high-speed circuit resistance training in healthy older adults. AAO 2022 conference, invited talk.

Katalina McInerney. Global Harmonization and Clinical Testing for AD/ADRD. Peru Alzheimer’s Disease Initiative (PeADI) scientific meeting in Lima, November 7, 2022

Katalina McInerney Practical Aspects of Study Collaboration Peru Alzheimer’s Disease Initiative (PeADI) scientific meeting in Cusco, November 8-12, 2022

A P P E N D I X 4

University of Miami Researchers on the Forefront of Alzheimer's and Dementia Research

The Evelyn F. McKnight Brain Institute and the Comprehensive Center for Brain Health were featured in the South Florida Hospital News and Healthcare Report.

H I G H L I G H T S O F W E B S I T E D E V E L O P M E N T , M E D I A

C O V E R A G E A N D / O R S O C I A L M E D I A A U D I E N C E D E V E L O P M E N T

Miller School Researchers Present High-impact Findings at World’s Largest Dementia Research Conference

By Lisette Hilton

Alzheimer’s and dementia experts with the University of Miami Miller School of Medicine presented on impactful research, including unique tools for early detection of cognitive decline and dementia, Alzheimer’s Disease genetic sequencing and much more at the recent 2022 Alzheimer’s Association International Conference (AAIC) in San Diego Miller School researchers contributed over 2 dozen presentations on a broad spectrum of topics at 2022 AAIC, the world's largest and most influential dementia research conference

An article published in the University of Miami INVENTUM and Research, Education & Medical News highlighted our EMBI researchers. Segments from the article are included below.

Drs. Galvin, Ramos, Camargo and Vontell were interviewed by various media teams at AAIC on their featured presentations.

Tatjana Rundek, M.D., Ph.D., professor of neurology, and scientific director of the Miller School's Evelyn F McKnight Brain Institute, and her Miller School team presented on the role of combined neuroimaging markers in cognitive decline and dementia “We have shown that MRI markers of white matter disease and ultrasound markers of atherosclerotic plaque in the carotid arteries are important predictors of cognitive decline beyond traditional vascular risk factors such as hypertension, diabetes, and hyperlipidemia,” Dr Rundek said “Their effect was consistent across different racial and ethnic groups ” Future research on these markers’ impact on could lead to interventions aimed at reducing the risk of future cognitive decline.

James Galvin, M.D., M.P.H., director of the Comprehensive Center for Brain Health and professor of neurology at the Miller School, presented research focused on early detection of cognitive impairment and understanding how risk and resilience factors explain differences in vulnerability to developing AD and related disorders across racial, ethnic and cultural groups. “While all physicians can diagnose mild cognitive impairment and AD and related disorders, the fact is that in the U.S. most diagnoses are not made until later stages of disease,” Dr. Galvin said. A key challenge with Alzheimer’s disease, he said, is that it’s difficult to assess a person’s brain health at the first visit and determine who is at risk and in need of a more extensive evaluation

William Keith Scott, Ph.D., executive director of the University of Miami Brain Endowment Bank, said his students presented two posters on their Ph D research projects One was research showing that the number of corpora amylacea (a circular structure that contains various waste products from cells) is associated with specific brain changes in people with AD Another poster highlighted work showing that inherited genetic variation in the mitochondrial genome may be associated with risk of dementia in Amish communities in Indiana and Ohio, and that this risk might be different in men and women “The volume of research being conducted on biomarkers, early detection, and longitudinal follow-up of cognitive impairment was overwhelming, and an indicator of how quickly that part of the field is developing,” Dr. Scott said.

Regina Vontell, Ph.D., assistant professor of neurology and associate director of the University of Miami Brain Endowment Bank, presented research focused on early detection of neurodegenerative changes seen in AD. “Our presentation investigated an important biomarker, neurogranin, which is detected in individuals with AD cognitive disorder. Our research shows that this protein is lost in specific regions in the brain’s hippocampus as the disease progresses We also show that there are structural changes to the neurons and the surrounding white matter in specific hippocampal regions,” Dr Vontell said

Lilah M. Besser, Ph.D., M.S.P.H., research assistant professor at the Comprehensive Center for Brain Health at the Miller School, said her team presented a literature review of published articles looking at associations between neighborhood greenspace exposure and AD and related dementia outcomes “Our goal as scientists was to determine the extent that studies included diverse racial/ethnic groups, the diversity of the studies’ geographic locations, and whether evidence suggests differences in associations depending on racial/ethnic group,” Dr. Besser said. The Miller school researchers found that nearly threequarters of studies found at least one positive association, such that individuals living in neighborhoods with more greenspace demonstrated better brain health outcomes.

Nutritional Intervention Studied in Cognitively Healthy

Older Adults

August 27,

2022

Christian Camargo, MD, discussed the design and feasibility of a fully virtual study testing the potential effects of Souvenaid — a once-daily multi-nutrient drink — on cognition in healthy aging adults in an exclusive MedPage Today interview.

Visual Impairment in Hispanic/Latinx People May Be Associated With Worse Measures of Cognition:

Understanding Brain Differences in MRI Markers, Sleep-Disordered Breathing of Latino Individuals:

Dr. Alberto Ramos, MD, MSPH, FAASM:

Dr Alberto Ramos discusses some of his research with the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), cerebrovascular risk factors and sleep:

In this Spanish interview, Dr Agudelo discussed how the quality of sleep could be affected by Daylight Saving Time The change in time, twice a year, in the United States has become a tradition, however, sleep experts indicate that perhaps we should say goodbye to this routine because Daylight Saving Time may not be beneficial for our health

Christian Agudelo, MD was interviewed on CNN regarding the time change and its effects on sleep and health.

Cuando dormimos profundamente, el cerebro se limpia de todas las tóxinas que genera durante el día, explica el neurólogo Christian Agudelo El médico analiza con la Dra. Azaret la importancia del sueño para tu corazón y cómo afecta a tu cuerpo el cambio de horario de verano a invierno

A new study led by researchers with the University of Miami Miller School of Medicine revealed that among older black adults, living in segregated versus more integrated neighborhoods is associated with a significant difference in cognitive processing speed

https://vjdementia com/speaker/lilah-besser/

https://physiciannews.umiamihealth.org/segregatedneighborhoods-associated-with-cognitivedecline-for-older-african-americans/

Lilah Besser Media

0 2 2 W E B S I T E R E D E S I G N

We redesigned our EMBI website mbi-umiami.org towards the end of 2021. The premise was to expand the site to serve as a unified information point about our EMBI leadership, organizational structure, collaborations, and partnerships and to be a resource for agerelated memory loss and cognitive impairment programs and activities. Our goal is to offer a wealth of resources on brain health and to be an interactive site with a large network of linked websites and resources. We used Google Analytics tracking to see who is visiting our site, where they come from, and where most time is spent. In addition to the general redesign, we have been implementing upgrades throughout the year such as adding social share buttons to our news posts and animating and linking our collaborators' umbrella to redirect to their respective sites (where possible).

In the coming years, we hope to attract more traffic to our site specifically through social media platforms like Facebook, Instagram, LinkedIn and Twitter. As we increase our efforts and interactions within these platforms, we hope to build more trust and familiarity with our followers by consistently providing them with helpful resources and valuable information. We often cross-link our different social media pages with our EMBI site and other verified UM pages. By increasing our visibility on these different platforms, we hope to establish credibility with our users and increase overall web traffic.

Jan1,2022-Dec31,2022

Over the past year, our website has seen an overall increase in performance, with a steady increase in traffic and engagement. We have seen an increase of 11.7% in new users, and visits to our webpage have grown by 10.4%. The time spent on the website has also increased by 14.4%.

One of our most recent improvements has been the implementation of social share buttons on each of the News Posts on our website. We hope this will increase interaction between our social media and website. Additionally, we are working on posting news items, blog posts, and other educational content on our website that can be linked to our social media posts, driving more traffic to the website. Examples of content we recently shared include information about sleep, The MIND Diet, and Neuroplasticity of the Brain & Physical Exercise.

This figure shows how users got to our webpage. Most commonly, users searched for us via organic search engines like Google. The second most common way of reaching our site was by directly typing in the EMBI URL. Other common routes were through social media or referrals from another medium. We have started sharing links to our new blog post as well as to previous blogs written by our team. We will be using this approach more in 2023, and will add more original articles and posts to our website.

New Blog post from Dr. Kaur about achieving better sleep, and the role of the glymphatic system in brain health

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Our social media continues to grow both in interaction and in the number of platforms we have a presence on. We have been posting more regularly on platforms we were already using and have opened new accounts in order to broaden our reach This year we created accounts on major platforms (Instagram and Linkedin) as well as some smaller local accounts such as Nextdoor. We've seen a steady growth in our reach on all Meta platforms. Our Facebook reach for this year saw over 20k% (1621) growth from last year, while our newer Instagram page which was created in July of 2022 is up to 200 in reach and 50 followers. This new account still has room for growth, and we will continue to push content to gain followers in 2023. We hope that as we grow these social media accounts, they will be utilized not only for research study recruitment, but for outreach and education in our communities. CLICK SOCIAL ICONS TO

Throughout 2022, we experienced a significant increase in our Facebook and Instagram reach. Through a combination of engaging content and strategic partnerships, we have been able to expand our online presence and to reach a wider audience. Our new LinkedIn account has seen the fastest growth, most of which is in the Miami-Fort Lauderdale Area.

We plan on working diligently in the coming year on more organized and strategic social media campaigns in an effort to connect with our audience and provide value through our content, as well as use our content to drive traffic to the Miami EMBI website. Our goal is to provide valuable educational content for our community so that they engage more with our social media accounts, as we work towards becoming a trusted source for new research and credible information on healthy brain aging.

F U T U R E P L A N S

Develop campaign goals: We plan on working towards increasing awareness of the University of Miami EMBI and our mission, research recruitment, and advertising and publicity for educational events.

Target audience: We are currently targeting people over 40 in Florida. With that in mind, we will be focusing more heavily on Facebook, Instagram, and Twitter, as well as LinkedIn for more professional development and scientific posts.

Develop campaign messaging: We will be focusing on creating messaging that will resonate with older adults, focusing heavily on healthy cognitive aging.

Create content: We plan to develop a content calendar that outlines the types of posts we believe would be interesting and educational for our followers, as well as commenting on relevant topics in health and research.

Campaign promotion via ads: We have mostly stayed away from paid advertising. However, for certain events and important messaging, it may be worth looking into, as social media ads are far more affordable than many other types of advertising and have the ability to reach more people than many traditional forms of advertising. As our followers grow, we also hope more people will find our content interesting enough to share, thus helping to increase our reach.

Measure and analyze: Towards the end of this year, we decided to invest more heavily in our social media through the purchase of Loomly. This tool not only allows us to post simultaneously to multiple platforms, but finally allows us to see advanced analytics overview of the posts' performance. This kind of insight will allow us to learn what our viewers engage with so that we can fine-tune our posting strategy and achieve better results in the future.

A P P E N D I X 5

E V E L Y N F . M C K N I G H T

In 2022, Christian Agudelo, MD, has continued his scholarship He has been meeting regularly with his mentoring team, Drs. Rundek, Sun, and Ramos, to track and evaluate the progress according to the goals of his Individual Development Plan.

This year, Dr Agudelo published 2 manuscripts, one in the the Journal of Applied Sciences (as first author) and another in Journal of Alzheimer’s Disease (as corresponding author). He also submitted a third manuscript for publication to Stroke (as first author), which is pending peer-review. Dr. Agudelo was also co-author on 4 abstracts accepted for presentation, 2 at the Annual Meeting of the Associated Professional Sleep Societies (Sleep 2022, Charlotte, NC) and 2 at the Alzheimer's Association International Conference (AAIC 2022, San Diego, CA). References for these are below.

Dr Agudelo was very active in grant submissions this year He was just awarded an NIH supplement (details presented below) and invited by the NIH to submit an R03 to extend this line of research.

N E U R O C O G N I T I V E S C H O L A R U P D A T E

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P U B L I S H E D R E F E R E E D M A N U S C R I P T S

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Agudelo C, Ramos AR, Sun X, Kaur S, Del Papa DF, Kather JM, Wallace DM. Alzheimer’s Disease Neuroimaging Initiative (ADNI). Sleep Disordered Breathing Risk with Comorbid Insomnia is Associated with Mild Cognitive Impairment Applied Sciences 2022 February 25; 12(5):2414

Rundek T, Del Brutto VJ, Goryawala M, Dong C, Agudelo C* , Saporta AS, Merritt S, Camargo C, Ariko T, Loewenstein DA, Duara R, Haq I. Associations Between Vascular Risk Factors and Perivascular Spaces in Adults with Intact Cognition, Mild Cognitive Impairment, and Dementia. J Alzheimers Dis. 2022 September 13; 89(2):437-448 PubMed ID: 35871327 *Corresponding author

M A N U S C R I P T S U N D E R R E V I E W

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Agudelo C, Ramos AR, Gardener H, Cheung K, Elkind MSV, Sacco RL, Rundek T. Sleep duration is associated with subclinical carotid plaque burden Stroke Submitted for peer review on 11/29/2022

A C C E P T E D R E F E R E E D A B S T

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S A N D P O S T E R S

Gonzalez, KA; Tarraf, W; Stickel, AM; Kaur, S; Agudelo, C; DeCarli, C; González, HM; Ramos, AR; Sleep duration and brain MRI measures: preliminary results from SOL-INCA MRI study. Annual Meeting of the Associated Professional Sleep Societies; Charlotte, NC; June 2022 (Refereed abstract)

Ramos, A; Gonzalez, K; Tarraf, W; Redline, S; Patel, S; Stickel, A; Agudelo, C; Kaur, S; Testai, F; Lipton, R; Isasi, C; Sotres-Alvarez, D; Gallo, L; DeCarli, C; Gonzalez, H; Sleep Disordered Breathing and MRI Makers of Brain Aging in the Hispanic Community Health Study/Study of Latinos. Annual Meeting of the Associated Professional Sleep Societies; Charlotte, NC; June 2022 (Refereed abstract)

R A

T

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Haq, IU; Del Brutto, V; Goryawala, M; Dias Saporta, AS; Merritt, SS; Camargo, C; Agudelo, C; Ariko, T; Dong, C; Loewenstein, D; Duara, R; Rundek, T; Association of enlarged perivascular spaces (ePVS) and MRI markers of small vessel disease (SVD) and neurodegeneration in the Florida Vascular Imaging Phenotypes (FL-VIP) Study of AD Risk. Alzheimer's Association International Conference; San Diego, CA; August 2022 (Refereed abstract)

4.

Rundek, T; Del Brutto, V; Goryawala, M; Dias Saporta, AS; Merritt, SS; Camargo, C; Agudelo, C; Ariko, T; Dong, C; Loewenstein, D; Duara, R; Haq, IU; Determinants of enlarged perivascular spaces (ePVS) on MRI: The Florida Vascular Imaging Phenotypes (FL-VIP) Study of AD risk. Alzheimer's Association International Conference; San Diego, CA; August 2022 (Refereed abstract)

D R . A G U D E L O ’ S A C H I E V E M E N T S , A W A R D S A N D R E C O G N I T I O N S I N C L U D E :

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He was awarded a Diversity Supplement to his mentor’s (Dr. Alberto Ramos) NIH R01 grant, Sleep in Neurocognitive Aging and Alzheimer's Research (SANAR, NIA R01 AG067568) Upon the release of funds, this award will support 75% of Dr. Agudelo’s effort toward research for two years and provide funds for travel to conferences.

2. 3. 4.

He submitted an application for a renewal of his current NIH Loan Repayment Program award This award provides $50,000 per year to pay for his eligible federal undergraduate and medical school debt

He submitted an invited letter of intent for an R03-type award for the Charleston Conference on Alzheimer’s Disease in September 2022.

He was selected and attended the 2022 Programs to Increase Diversity Among Individuals Engaged in Health Related Researchs (PRIDE) Dr Agudelo was specifically selected to attend the Behavioral Medicine and Sleep Disorders Training Institute of PRIDE, which was a 2-week inperson career development workshop hosted by the Univeristy of Miami Milller School of Medicine in 2022.

5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

He mentored a neurology resident at the University of Miami, Dr Dylan F Del Papa, who won first prize for a poster presentation at the 2022 University of Miami Department of Neurology Resident Research Day. (Sleep Disordered Breathing Risk with Comorbid Insomnia is Associated with Mild Cognitive Impairment)

He attended and presented at the data blitz of the 13th Annual McKnight InterInstitutional Meeting in March 2022 in Tucson, AZ

He joined the Editorial Board of Frontiers in Neurology in June 2022.

He joined the Editorial Board of the Journal of Alzheimer’s Dementia in July 2022

He completed a manuscript review for the journal Frontiers in Psychiatry in August 2022.

He completed a manuscript review for the journal Sleep Advances in August 2022

He completed a manuscript review for the journal Frontiers in Sleep in September 2022.

He was interviewed by CNN en Español in April 2022, discussing daylight saving time, sleep apnea and brain health

He was interviewed by CNN en Español in November 2022, discussing standard time and sleep apnea, and brain health.

As part of the McKnight Community Education Program, he presented in the Miami-Dade Public Library lecture series, Maintaining A Healthy Aging Brain. He discussed How to Sleep to Maintain Brain Health on July 12, 2022.

As part of the McKnight Community Education Program, he presented in the Miami-Dade Plublic Library lecture series, Living with Low Vision. He discussed How to Sleep to Maintain Brain Health on October 8, 2022.

Dr Agudelo’s program of research has an overarching theme to identify modifiable sleep-related biomarkers of cognitive aging. Ultimately, his goal is to modify sleep to ameliorate cognitive decline. By leveraging excellent mentorship, ongoing research within the University of Miami McKnight Brain Institute, his affiliation with the Hispanic Community Health Study/Study of Latinos, and access to Alzheimer’s Disease Neuroimaging Initiative (ADNI) data, Dr Agudelo developed three projects, of which one is completed As the Evelyn F McKnight Neurocognitive Scholar, Dr Agudelo has obtained the training and mentorship needed to complete Project 1, obtain NIH funding for Projects 2, translate project 3 into an integral part of his upcoming NIH K23 award application (Mentored Patient-Oriented Research Career Development Awards), and develop project 4 into an upcoming NIA R03 award application (Grants for Early Medical/Surgical Specialists' Transition to Aging Research)

Project 1: The association between co-morbid insomnia and sleep disordered breathing and mild cognitive impairment in the ADNI study.

Disrupted sleep has been associated with cognitive decline Few studies have evaluated associations between sleep disordered breathing (SDB) with comorbid insomnia and mild cognitive impairment (MCI). Using Alzheimer’s Disease Neuroimaging Initiative data, he evaluated cross-sectional associations between SDB with insomnia status and MCI. He included ADNI participants with normal cognition or MCI. Insomnia was defined by self-report. SDB risk was assessed by modified STOP-BANG He created logistic regression models to evaluate associations between four sleep disorder subgroups (low risk for SDB alone, low risk for SDB with insomnia, high risk for SDB alone, and high risk for SDB with insomnia) and MCI. Models adjusted for age, sex, BMI, APOE4 genotype, race, ethnicity, education, marital status, hypertension, cardiovascular disease, stroke, alcohol abuse, and smoking. The sample (n=1,391) had a mean age of 73.5±7.0 years 44 9% were female 72 0% were at low risk for SDB alone, 13 8% at low risk for SDB with insomnia, 10 1% at high risk for SDB alone, and 4 1% at high risk for SDB with insomnia. Only high risk for SDB with comorbid insomnia was associated with higher odds of MCI (OR 3.22, 95% CI 1.57-6.60). These findings inform the approach to current and future projects. In studies examining insomnia, Dr. Agudelo will adjust for sleep apnea.

Project 2: Obstructive sleep apnea may be a modifiable risk factor for cognitive disease mediated by the loss of gray matter microstructure integrity.

Project 2 is the topic of a recently awarded 2-year Diversity Supplement to Dr. Alberto Ramos’ existing R01 grant, SANAR (R01 AG067568). SANAR is determining the relationship between obstructive sleep apnea (OSA) and vascular determinants of cognitive decline among US Hispanic/Latino adults, who have >2-fold risk of dementia and early cognitive decline compared to non-Hispanic white adults. Trials of disease modifying therapies for cognitive disease have failed because they occur too late in the pathologic process. A critical gap in the development of effective therapy is the absence of (1) reliable preclinical biomarkers of cognitive disease associated with (2) modifiable risk factors of cognitive pathology To bridge this critical gap as a Supplement to SANAR, Dr Agudelo proposes that (1) gray matter (GM) microstructure integrity is a biomarker of preclinical cognitive decline, and (2) OSA is a modifiable risk factor for cognitive disease mediated by the loss of GM microstructure integrity. The primary aims of this project are (1) determine if prior and persistent exposures to OSA and OSA-related hypoxemic burden are associated with lower hippocampal GM microstructure integrity; (2a) determine if hippocampal GM microstructure integrity is associated with average 12-year cognitive change among participants with and without OSA; (2b) determine if hippocampal GM microstructure integrity mediates associations between OSA and 12-year average cognitive change; and (3) determine the independent and interactive association of non-dipping blood pressure and OSA with hippocampal GM microstructure integrity This study will use data from the multi-center community-based Hispanic Community Health Study/Study of Latinos, its completed ancillary studies (SOL-INCA, SOL-INCA MRI, Sueño), and the ongoing ancillary study (SANAR). Completed studies have acquired baseline self-reported sleep data, baseline and repeat cognitive evaluations 7 and 12 years after baseline, repeat portable sleep apnea tests 12 years after baseline, and MRI among 1,000 predominantly middled-aged and older participants with and without OSA and without cognitive disease MRI protocols included DTI, which measures GM microstructure integrity. SANAR is obtaining 24-hour ambulatory blood pressure monitoring (to measure non-dipping blood pressure, a feature of OSA) and repeat home sleep apnea tests (10 years later). This Diversity Supplement will fund 75% of his effort for two years.

Project 3: Mesial temporal lobe gray matter microstructure integrity as a marker of accelerated cognitive aging associated with sleep continuity and slow wave activity.

Project 3 will leverage data from Project 2 (the Diversity Supplement) and use data from the Hispanic Community Health Study/Study of Latinos Project 3 will be the basis of a mentored career development award application in 2023 (institutional KL2 or NIH K23). Dr. Agudelo proposes that (1) gray matter (GM) microstructure integrity is a marker of subclinical cognitive decline, (2) sleep continuity and slow wave activity during sleep are associated with lower GM microstructure integrity, and (3) lower GM microstructure integrity mediate a relationship between sleep and accelerated cognitive aging He hypothesizes that lower sleep continuity and lower slow wave activity during sleep are associated with lower GM microstructure integrity. Lower gray matter microstructure integrity, in turn, will mediate a relationship between sleep and accelerated cognitive aging. In addition to the measures used in Project 2, Project 3 will also use the sleep actigraphy data. This project will also propose the novel use of portable dry-lead electroencephalography (EEG) to measure sleep architecture, and specifically, slow-wave activity during sleep This project, as part of a 5-year career development award, will be the final stepping stone toward becoming an independent clinical scientist. He expects to submit this project as a mentored career development award application in the fourth quarter of 2023.

Project 4: Nap phenotypes and their association with cognition.

Project 4 will similarly leverage data from the Hispanic Community Health Study/Study of Latinos and serve as the basis for a 2-year NIA R03 award application (Grants for Early Medical/Surgical Specialists' Transition to Aging Research) Napping is an understudied phenomenon, and napping behaviors vary widely among different cultures and societies Furthermore, there are significant cultural and societal variations in napping behaviors Dr Agudelo proposes using the actigraphic data available for almost 2,000 participants of the Hispanic Community Health Study to determine how people nap. Specifically, using datadriven latent class analysis, phenotypes of napping can be developed that define different ways people nap regarding nap frequency, duration, timing, and selfreported daytime sleepiness He then will examine if any nap phenotypes are

associated with accelerated cognitive decline or protective against brain aging

This project will also leverage the portable dry-lead EEG proposed in Project 3. Project 4 will pilot the use of dry-lead EEG worn over multiple 24-hour periods, to capture the sleep architecture of napping in the real-world environment. This pilot will serve as proof of methodological concept and provide pilot data for a subsequent R01 grant application that incorporates portable EEG-derived sleep architecture into the study of napping, nap phenotypes, and cognitive aging

We are grateful for the funding to support Dr. Agudelo. As the Evelyn F. McKnight Neurocognitive Scholar, he has achieved the milestones needed to develop into an independent clinical scientist As of January 1st, 2023, he will be completely funded by his NIH Diversity Supplement, which will support his ongoing development and provide data needed for a competitive NIH K23 career development award application and beyond. He will join the Department of Neurology Faculty in June of 2023.