Miller School Among Most Represented Centers at World’s Largest Alzheimer’s and Dementia Meeting
With several dozen abstracts and multiple oral presentations, the John. P. Hussman Institute for Human Genomics and the Department of Neurology played a prominent role at the Alzheimer’s Association International Conference.
With several dozen abstracts and multiple oral presentations, the John. P. Hussman Institute for Human Genomics (HIHG) and Department of Neurology at the University of Miami Miller School of Medicine played a prominent role at the Alzheimer’s Association International Conference (AAIC).
Renowned for their Alzheimer’s disease genetic research, Hussman Institute faculty, postdocs and global collaborators presented more than 60 abstracts and several oral presentations, making it one of the highest-profile institutes at the meeting.
“From a scientific perspective, AAIC attracts experts across different domains, from basic scientists, geneticists and industry and technology leaders to clinicians and clinical researchers,” said Margaret Pericak-Vance, Ph.D., director of the Hussman Institute and the Dr. John T. Macdonald Foundation Professor of Human Genetics at the Miller School, who chaired the AAIC’s Prospective Special Session on Africa. “The importance of getting all those experts in one venue for face-to-face sharing and collaboration cannot be overstated in the quest to rid the world of dementia-related conditions.”
Delving into DAWN
Dr. Pericak-Vance leads one of the Hussman Institute’s largest ongoing projects, the DAWN Alzheimer’s Research Initiative, which involves four sites in the U.S. and sites in nine African countries that are part of the African Dementia Consortium. Alzheimer’s disease patients and non-cognitively impaired individuals are recruited to provide blood specimens for DNA and plasma for biomarker analysis as part of a global approach to prevention and treatment for Alzheimer disease. More than 60 international researchers from DAWN held an AAIC pre-conference workshop. The focus was on the next generation of scientists. Postdoctoral fellows presented their research from DAWN to the entire group, as well as members from the National Institute on Aging.
Dr. Pericak-Vance and DAWN collaborators Drs. Adesola Ogunniyi and Rufus Akinyemi from the University of Ibadan co-organized and moderated AAIC’s Featured Research Session, “Unraveling the Genetics, Biomarkers and Reducing the Burden of Dementia in Africa.”
The session featured talks by DAWN collaborators including Anthony J. Griswold, Ph.D., associate professor in the Dr. John T. Macdonald Foundation Department of Human Genetics and associate director of the Hussman Institute Center for Genome Technology, who presented, “Leveraging African Ancestry Diversity for Global Advances in Alzheimer’s Disease Genetics.” This talk highlighted the latest findings on the genetics of dementia, particularly in individuals of African ancestry. It included results from Biniyam Ayele, M.D., a neurologist from Ethiopia who is training in genomics at the Hussman Institute, who has identified several rare genetic variants that are unique to the African population.
Dr. Griswold chaired another session, “Biomarker Findings in Global Populations,” during which he looked at the preliminary findings on the plasma collected for the DAWN study.
“The results show that some of these biomarker profiles, particularly those related to neuroinflammation and neurodegeneration, differ slightly between Africans from the African continent and African Americans from the U.S.,” Dr. Griswold said. “This will impact how we design biomarker studies, as well as how we think about therapeutic outcomes and using them for disease diagnosis and monitoring at the global scale.”
Genetics and Function
The Hussman Institute researchers are working to understand the functional effects of genetic discoveries. Liyong Wang, Ph.D., research associate professor of human genetics at the Miller School, presented an abstract describing the group’s new functional tool, Enhanced Hi-C capture analysis (eHiCA) and its application to genome-wide association studies (GWAS). Luciana Bertholim Nasciben, Ph.D., an assistant scientist at the Hussman Institute, presented data on the strong, protective locus for APOE4 carriers that Hussman Institute investigators have found in people of African ancestry. She showed that the protective locus is traveling with an unusually large structural variant that contains DNA known to control APOE and other genes.
“One of the challenges over the past decade is understanding what the precise genes are that are found through GWAS studies, as most disease-associated regions lie in the regulatory areas of the genome and which exact gene they are interacting with is not known,” said study lead Jeffery M. Vance, M.D., Ph.D., professor of human genetics and neurology and director of the Center for Genomic Education and Outreach at the Miller School. “eHiCA is a very flexible approach using HiC, a chromatin 3D approach, that now allows us to see what genes are interacting with the GWAS-associated regions, a long desired finding. APOE4 is the strongest genetic risk factor for Alzheimer’s disease and is carried by about half of all AD patients. Identifying the protective mechanism in African ancestry is thus a key target for discovery. Both studies move us one step closer to using these genetic discoveries towards therapeutic interventions.”
Alzheimer’s Risk, Cognitive Health
Brian W. Kunkle, Ph.D., M.P.H., assistant professor of human genetics and head of the Genetic Epidemiology Division in the Center for Genetic Epidemiology and Statistical Genetics at the Miller School, presented findings on genetic risk for Alzheimer’s based on sex. Oladotun Olalusi, a Nigerian neurologist and assistant scientist at the Hussman Institute, gave a presentation on emerging risk factors for cognitive dysfunction among older Nigerians. Daniel Dorfsman, Ph.D., a Hussman Institute postdoctoral fellow, presented on genetic variants in HIVEP3 being associated with cognitive “superaging” in the Amish.
While the HIVEP3 gene has been implicated in the biology of Alzheimer’s disease, this study suggests there may be variants of the gene that preserve episodic memory, according to the study’s senior author, William K. Scott, Ph.D., professor of human genetics at the Miller School and co-director of the University of Miami Brain Endowment Bank.
“We studied 2,000 Amish people and found 83 superagers, defined as people who had the episodic memory of someone in their mid-40s despite being older than 80 years, and reported at AAIC that 95% of the superagers in our study carried at least one of the protective variants of the HIVEP3 gene,” Dr. Scott said. “This suggests that HIVEP3 is not just a risk factor for Alzheimer’s disease but there may be a form of the gene that contributes to exceptional memory.”
Finally, Makaela Mews, a researcher from Case Western Reserve University, reported on data from Dr. Griswold’s NIH-funded Multi-Ancestry Genomics, Epigenomics, and Transcriptomics of Alzheimer’s (MAGENTA) study.
“The MAGENTA study highlights differences in how genes are being regulated across ancestries and how that might impact how we think about Alzheimer’s disease pathology,” Dr. Griswold said.
Neurologists Share Data, Expertise
Miller School faculty from the UM Brain Endowment Bank, Evelyn F. McKnight Brain Institute, Comprehensive Center for Brain Health (CCBH) and Center for Cognitive Neuroscience and Aging shared novel findings and insight on new and investigational Alzheimer’s disease drugs and new ways to diagnose and assess cognitive decline and environmental impacts on cognitive health, according to James Galvin, M.D., M.P.H., professor of neurology at the Miller School, chief of the Division of Cognitive Neurology, founding CCBH director and director of the Lewy Body Dementia Research Center of Excellence.
Dr. Galvin’s presentations featured topline results from a phase II study of the investigational drug zervimesine for treatment of dementia with Lewy bodies (DLB). He also presented initial results from a population-based study of Alzheimer’s disease in American Samoa.
In a featured research session, Dr. Galvin presented on the COG1201 SHIMMER study (NCT05225415), in which he and colleagues evaluated 130 adults with mild-to-moderate DLB. Participants were randomly assigned to a daily oral dose of zervimesine or placebo for six months. SHIMMER showed zervimesine had a positive impact on neuropsychiatric, cognitive, motor and functional symptoms, according to Dr. Galvin.
“Patients with DLB who were treated with zervimesine scored an average of 86% better than patients receiving placebo on the neuropsychiatric inventory (NPI-12), a tool that measures 12 separate behavioral symptoms that are hallmarks of DLB,” according to meeting coverage by Psychiatric Times.
“Hallucinations, delusions and anxiety, measured by NPI-12, are considered among the most troubling to patients and caregivers, which made zervimesine’s impact even more notable,” Dr. Galvin said in the article.
New Data on Approved Drug for Early Alzheimer’s
AAIC 2025 offered a high-visibility venue for the Miller School Department of Neurology’s extensive research on the recently approved lecanemab for early Alzheimer’s disease. A study on the real-world use of lecanemab in early Alzheimer’s disease suggests that most patients maintain their cognitive abilities without significant progression of the disease.
“However, some patients experienced side effects, which were generally manageable,” according to Christian J. Camargo, M.D., assistant professor of cognitive neurology at the Miller School and study co-author.
Miller School researchers also reported on studies showing potential disparities in the use of lecanemab in Black patients, findings that high-risk groups taking the drug, including those on blood thinners, experienced no severe bleeding events and data suggesting that neurologists using lecanemab report high satisfaction with the drug.
“We shared our findings from a study looking at how patients are diagnosed and treated with lecanemab across various health care settings, the outcomes from which will help to optimize care pathways to improve access and treatment success,” Dr. Camargo said. “One of our oral presentations also looked at how the use of blood tests to diagnose Alzheimer’s is becoming more common, offering a less invasive and potentially quicker alternative to traditional methods.”
Environmental Impacts on Cognitive Decline
AAIC featured posters by Lilah Besser, Ph.D., M.S.P.H., research assistant professor of neurology at the Miller School and the CCBH, looking at topics such as neighborhood greenness in midlife and its association with cognitive decline in later life.
“In this multi-site U.S. study, we found that individuals who lived in greener neighborhoods during midlife (from 45 to 54 years of age) had slower decline in processing speed over time in later life, or when 55 years and older,” Dr. Besser said.
In another poster looking at associations between neighborhood-built environment characteristics and cognitive function in a population of older adults living in southcentral Florida, Dr. Besser and colleagues found that the associations between neighborhood open/park space and retail space and global cognitive function varied significantly depending on neighborhood socioeconomic status.
And in a “Healthy Brain Initiative” poster, Dr. Besser and her team shared that middle- to older-age adults in South Florida with higher systemic inflammation who had greater neighborhood tree canopy access tended to have better brain health.
Novel Approaches to Brain Health Assessment
Michael Kleiman, Ph.D., research assistant professor of neurology at Miller School and the CCBH, presented three posters this year, including “The Brain Health Index: Integrating Vulnerability, Resilience, and Functioning Into a Unified Measure of Cognitive Health and Neurodegenerative Risk.”
“This examines a new index we created that combines measures of modifiable and non-modifiable risk factors of pathology-independent cognitive impairment,” he said. “I also presented ‘Automated Scoring of Narrative Recall Assessments Using Large Language Models Enables Exploration of Alternate Scoring Criteria,’ which summarizes my study on large language models (LLMs), which scored neuropsych assessments as accurately as humans. It demonstrates a method to test new scoring criteria using LLMs to quickly test the accuracy of each scoring criteria strategy.”
Dr. Kleiman’s research on his “Puppy Escape” narrative shows an ability to detect preclinical Alzheimer’s disease with only a 15-minute delay compared to the 30-minute delays in standard narratives.
Tags: Alzheimer's disease, APOE 4 gene, Brain Endowment Bank, Center for Cognitive Neuroscience and Aging, Comprehensive Center for Brain Health, dementia, Department of Neurology, Dr. Anthony Griswold, Dr. Brian Kunkle, Dr. Christian Camargo, Dr. James Galvin, Dr. Jeffery Vance, Dr. John T. Macdonald Foundation Department of Human Genetics, Dr. Lilah M. Besser, Dr. Liyong Wang, Dr. Margaret Pericak-Vance, Dr. Michael Kleiman, Dr. William Scott, Evelyn F. McKnight Brain Institute, genetics, genomics, John P. Hussman Institute of Human Genomics, Lewy body dementia