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We are a scientific community of clinicians and researchers and we partner with the University of California, San Francisco (UCSF) and the San Francisco VA Health Care System (SFVAHCS) to bring the power of modern medicine to the health of our nation’s Veterans.

Congratulations to Dr. Bruce Ovbiagele for his recent awards!

NCIRE-supported scientist and Board Member Dr. Bruce Ovbiagele has been announced as a recipient of the American Neurological Association’s (ANA) 2022 scientific awards for Outstanding Accomplishments in Academic Neurology and Neuroscience.

The ANA announced that Dr. Ovbiagele will be receiving the Audrey S. Penn Lectureship Award, which is bestowed upon ANA members who conduct outstanding research, program-building, or educational scholarship to promote health equity and address health care disparities.

These prestigious awards recognize leaders in academic neurology and neuroscience who have exemplified excellence in research, teaching, and clinical practice across the breadth of clinical neurology and neuroscience disciplines.

The Awards will be presented during the 147th ANA Annual Meeting, to be held October 22–25, 2022 at the Hyatt Regency in Chicago, Illinois.

Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, FANA, is a vascular neurologist, clinical epidemiologist, and health equity scholar, with a focus on reducing the burden of stroke. He is Professor of Neurology and Associate Dean at UCSF, as well as Chief of Staff with the San Francisco VA Health Center System. Dr. Ovbiagele leads several funded programs focused on improving stroke outcomes among vulnerable and underserved populations, as well as mentoring early career scholars.

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The Polygenic Risk Score Knowledge Base offers a centralized online repository for calculating and contextualizing polygenic risk scores

The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. So NCIRE-supported scientist, Michael Weiner, MD, and his colleagues developed a centralized polygenic risk score calculator that currently contains more than 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to easily calculate sample-specific polygenic risk scores with comparable results to other available tools. Polygenic risk scores are calculated either online through the Polygenic Risk Score Knowledge Base (PRSKB; https://prs.byu.edu) or via a command-line interface.

In their co-authored article, published in Nature, the cohort present the streamlined analysis tool that can provide study-specific polygenic risk scores across the UK Biobank, 1000 Genomes, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), contextualize computed scores, and identify potentially confounding genetic risk factors in ADNI. With this tool and web interface to calculate and contextualize polygenic risk scores across various studies, Dr. Weiner and the team anticipate that it will facilitate a wider adaptation of polygenic risk scores in future disease research.

Michael Weiner, MD is a Professor, Radiology with the UCSF School of Medicine, and Principal Investigator of ADNI, a longitudinal study aimed at validating biomarkers for Alzheimer’s. He also launched BrainHealthRegistry.org, aimed at accelerating treatment development for brain diseases.

ADNI, which began in 2004 under Weiner’s leadership, is the most extensive Alzheimer’s observational study globally and considered by many to be the gold standard for clinical trials for the disease. The study has attracted more than 2,000 subjects since 2004 at 60 sites across the U.S. and Canada.

Major study of Alzheimer’s disease to focus on including people from underrepresented communities

The Northern California Institute for Research and Education (NCIRE) has received a $147 million grant from the National Institute on Aging (NIA) to continue the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The ADNI project, led by principal investigator Dr. Michael W Weiner, Professor of Radiology, Medicine, Psychiatry, and Neurology at UCSF, was founded in 2004 with the goal of validating biomarkers for Alzheimer’s disease clinical trials. ADNI has enrolled over 2000 participants, monitoring them longitudinally using imaging assessments, and cognitive, genetic, cerebrospinal fluid and blood tests. Results of this project have had a major impact on Alzheimer’s disease research and clinical trials, and have yielded over 4500 publications.

While much progress has been made since the start of ADNI in better understanding Alzheimer’s disease and developing therapies to slow or prevent disease, the vast majority of research has been conducted in predominantly non-Hispanic White and well-educated populations. The degree to which results can be generalized to other groups that are underrepresented, such as Black/African-American, Hispanic/Latinx, Asian, Pacific Islander and American Indians, and people with less than a high school education, is unknown. These diverse ethnocultural and educational groups have historically been under included in medical research and clinical trials, yet differ in their prevalence of dementia from non-Hispanic White Americans. To understand the reasons underlying differences, and to determine the generalizability of results, large cohorts of people from these groups are urgently needed.

The new grant will fund a five year extension of the study, termed ADNI4, set to begin this month. Importantly, between 50 and 60% of its participants will be from under-included groups. To enroll and monitor these elders, ADNI4 will use a variety of innovative techniques. To engage these groups, it will use digital marketing and social media campaigns, including locally branded websites, to provide communities with information about the study and recruit up to 20,000 participants to join the online phase of the study. Through a web-based portal, ADNI4 will screen up to 20,000 elders using digital cognitive tests including a novel voice assessment tool provided by Novoic Ltd. From that online study group, 4000 participants will be further screened using remote collection of blood samples to identify people at risk for AD.

Additionally, ADNI will employ a culturally engaged research approach which includes identifying “hub regions” - areas that have both significant populations of underrepresented groups and an Alzheimer’s disease research center. Study liaisons will connect with local community groups in hub regions and will help direct elders to the study and guide them through the study processes. Ultimately, ADNI aims to enroll 500 new participants for detailed in-clinic assessments.

This combination of innovative approaches, described in Alzheimer’s & Dementia: the Journal of the Alzheimer’s Association in a publication by Dr. Weiner and colleagues [1], represents a unique strategy with the potential to both determine the generalizability of current Alzheimer’s disease knowledge, and to address long-standing ethnocultural and educational disparities and inequities in medical research. The renewal of ADNI by the NIA will ensure that this high impact project will continue to improve methods to diagnose and ultimately treat Alzheimer’s disease.

[1] Weiner MW, Veitch DP, Miller MJ, Aisen PS, Albala B, Beckett L, et al. Increasing participant diversity in AD research: plans for digital screening, blood testing, and a community-engaged approach in the Alzheimer’s Disease Neuroimaging Initiative 4. Alzheimer's & Dementia. 2022. DOI: 10.1002/alz.12797

Learn More: https://adni.loni.usc.edu/

https://www.va.gov/san-francisco-health-care/

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Rebecca Sudore receives GeriPal Mentor of the Year Award!

Congratulations to NCIRE-supported Scientist Rebecca Sudore, MD for receiving the 2022 GeriPal Mentor of the Year award! This nomination from the University of California, San Francisco graduating fellowship class reflects Dr. Sudore’s excellence in teaching, clinical care, research mentorship and her dedication to fostering creative, scholarly, and professional growth of mentees in Geriatrics and Palliative Care.

Rebecca Sudore, MD is a Staff Physician, Geriatrics Service with the SF VA Health Care System, and Professor of Medicine at UCSF.

UCSF’s innovative two-year integrated geriatrics and palliative care (geripal) fellowship aims to develop physician leaders in the care of older adults with serious illness.

Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms.

In a study published in The Journal of Neuroscience (JNeurosci), NCIRE-supported Investigator, Thomas Neylan, MD, and his colleagues found evidence that suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.

Thomas Neylan, MD is a Staff Physician, Mental Health Service, and Posttraumatic Stress Disorders (PTSD) Clinic and the Stress and Health Research Program with the SF VA Medical Center, and Professor in Residence of Psychiatry at UCSF.

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