One Mission, One Goal: Veterans Health

About NCIRE

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.

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.

Dr. Bruce Ovbiagele, receives the National Medical Association’s Meritorious Achievement Award

NCIRE-supported Investigator and Board Member, Dr. Bruce Ovbiagele was honored with the National Medical Association (NMA)’s Meritorious Achievement Award at the NMA Annual Convention and Scientific Assembly in Atlanta, Georgia, July 30 - August 3, 2022.

This award is given for noted national and international achievement and prominence.

The National Medical Association (NMA)’s Annual Convention and Scientific Assembly is acclaimed as the nation’s foremost forum on medical science and African American health. Each year, African American physicians, and other health professionals from across the country convene to participate in the scholarly exchange of medical advances, discuss health policy priorities, and to share experiences. Through NMA’s 26 Scientific Specialty Sections, the Convention attracts the broadest spectrum of African American physicians, academicians, and scientists in the country.

Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS 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 Care System.

Traumatic brain injury and post-traumatic stress disorder are not associated with Alzheimer's disease pathology measured with biomarkers

Traumatic brain injury (TBI) is often associated with long-term consequences including cognitive impairment and neurological disease. A history of moderate to severe TBI has been associated with an approximate doubling of the risk of all-cause dementia. Post-traumatic stress disorder (PTSD) is a psychiatric disorder that may follow exposure to traumatic stress including military combat. Like TBI, PTSD has been associated with the development of dementia in later life6, 7 although evidence for this association is mixed. TBI and PTSD are commonly comorbid.

NCIRE-supported Investigators Drs. Michael Weiner and Thomas Neylan, with colleagues, tested the hypothesis that non-demented veteran elders with TBI and/or PTSD have elevated AD and cerebrovascular pathology compared to their veteran counterparts without lifetime TBI and/or PTSD, using the framework of the Alzheimer's Disease Neuroimaging Initiative (ADNI).

The co-published study, sponsored by the U.S. Department of Defense, identified 289 non-demented veterans with TBI and/or PTSD and controls who underwent clinical evaluation, cerebrospinal fluid (CSF) collection, magnetic resonance imaging (MRI), amyloid beta (Aβ) and tau positron emission tomography, and apolipoprotein E testing. Participants were followed for up to 5.2 years.

The study found that TBI and/or PTSD were not associated with elevated Alzheimer’s Disease biomarkers. The poorer cognitive status of exposed veterans may be due to other comorbid pathologies.

Thomas Neylan, MD, is a Professor, In Residence in the Department of Psychiatry at the University of California, San Francisco. He is the Director of the Posttraumatic Stress Disorders (PTSD) Clinic and the Stress and Health Research Program at the San Francisco Veterans Affairs Medical Center.

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 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.

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Dr. Li-Wen Huang named 2022 Grunfeld Scholar

NCIRE-supported Investigator Dr. Li-Wen Huang was announced as a 2022 Grunfeld Scholar by the San Francisco VA Health Care System (SFVAHCS).

The SFVAHCS selected two promising medical researchers for the Grunfeld Scholars Research Development Initiative. This initiative, currently in its third year, invests in early-career clinician-scientists to grow the pipeline of future leaders in medical research related to the health of Veterans, and preserve SFVAHCS’ legacy as a pre-eminent medical research institution.

The Grunfeld Scholars Research Development Initiative is named for Carl Grunfeld, MD, PhD, SFVAHCS’ Associate Chief of Staff for Research and Development. Dr. Grunfeld is a renowned clinician-scientist who has contributed over four decades of research excellence to the SFVAHCS. Dr. Grunfeld also serves on the NCIRE Board of Directors.

Li-Wen Huang, MD is an Assistant Professor in the UCSF Division of Hematology/Oncology in the Department of Medicine and a medical oncologist taking care of older patients with hematologic malignancies at the SFVAHCS.

Dr. Michael Steinman, MD Interviewed on the NavNeuro Podcast

Michael Steinman, MD, an NCIRE-supported Investigator, discusses polypharmacy, inappropriate polypharmacy, deprescribing as an intervention, specific drug classes with potential for cognitive side effects in older adults, and a neuropsychologist’s role in clinical care related to polypharmacy.

Dr. Steinman is a Staff Physician, Geriatrics, Palliative and Extended Care Service Line with the San Francisco VA Health Care System, and a Professor of Medicine at UCSF.

Listen Here: https://www.navneuro.com/96/

Do functional status and Medicare claims data improve the predictive accuracy of an electronic health record mortality index? Findings from a national Veterans Affairs cohort

NCIRE-supported researcher Sei Lee, MD, MAS, who is a Professor of Medicine at UCSF, and Staff Physician, Geriatrics, Palliative and Extended Care Service Line with the San Francisco VA Health Care System, co-published a study that assessed whether adding functional status and/or Medicare claims data (which are often not available in EHRs) improves the accuracy of a previously developed Veterans Affairs (VA) EHR-based mortality index.

The retrospective cohort study followed 62,014 Veterans aged 75 years and older enrolled in VA primary care clinics from January 2014 to April 2020 and was published in the BMC Geriatrics journal.

Meddling in the affairs of heart and lungs: How secondhand tobacco smoke affects the complex interactions between heart and lungs.

It is known that exposure to secondhand tobacco smoke – even in the distant past – is associated with reduced exercise capacity and abnormal lung function with air trapping in the lungs. However, what is not clearly known is the cardiovascular health effects of remote exposure to secondhand smoke. In a new study, which was funded by a research award from the Flight Attendant Medical Research Institute and published in the BMJ Open Respiratory Research, NCIRE-supported Investigator Mehdrad Arjomandi, MD, and colleagues found that past secondhand smoke exposure was associated with exercise capacity due to effects on both the lungs and the heart.

The research team evaluated the health effects of remote exposure to secondhand smoke in nearly 250 never-smoking flight attendants who had worked in smoky aircraft cabin before smoking was banned on commercial airlines. They found the secondhand smoke exposure was associated with reduced exercise capacity both because of direct effects on cardiac output, also because air trapping in the lungs affected the heart. These findings suggest the presence of subtle cardiopulmonary pathology related to prolonged past exposure to secondhand smoke impairs the oxygen carrying machinery, which could be disadvantageous during the times of increased stress or disease.

This study brings a deeper understanding of how secondhand smoke exposure continues to affect the heart, lungs, and exercise capacity years later.

Dr. Arjomandi is a Professor of Medicine at UCSF, and Assistant Professor in residence and the Director of Environmental Medicine Clinic with the San Francisco VA Health Center System.

Serious Illness Communication in Cancer Care in Africa: A Scoping Review of Empirical Research

Serious illness communication (SIC) in cancer care describes conversations between clinicians, patients, and families about prognosis and treatment decisions. Yet, cultural context influences SIC.

NCIRE-supported researcher Rebecca Sudore, MD, Staff Physician, Geriatrics Service at San Francisco VA Health Care System and Professor of Medicine, UCSF, joined fellow researchers to describe and synthesize the heterogeneous body of research on SIC practices, preferences, and needs in Africa to identify research and training priorities.

In their study, published in JCO Global Oncology, an American Society of Clinical Oncology Journal, the investigators identified 42 studies out of 1811 unique titles that focused on SIC within cancer or palliative care in Africa. The cohort found that research on SIC in Africa has increased in recent years. Most studies have focused on information delivery by clinicians; fewer on eliciting information from patients (e.g., shared decision-making, advanced care planning). Significant opportunities exist for further study and for communication skills training.

Congratulations to Barbara Bensing, PhD and Paul Sullam, MD for their recently published studies!

NCIRE-supported investigator Barbara Bensing, PhD co-authored the following published studies:

Molecular recognition of sialoglycans by streptococcal Siglec-like adhesins: toward the shape of specific inhibitors

Publication: RSC Chemical Biology, Oct 18, 2021

https://pubmed.ncbi.nlm.nih.gov/34977577/

O-linked α2,3 sialylation defines stem cell populations in breast cancer

Publication: Science Advances, January 7, 2022

https://pubmed.ncbi.nlm.nih.gov/34995107/

Paul Sullam, MD, a fellow NCIRE-supported investigator, joined his colleague Dr. Bensing to co-author the following studies:

Proteoglycan 4 (lubricin) is a highly sialylated glycoprotein associated with cardiac valve damage in animal models of infective endocarditis

Publication: Glycobiology, August 25, 2021

https://pubmed.ncbi.nlm.nih.gov/34459483/

Origins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation.

Publication: Nature Communications, May 18, 2022

https://urldefense.com/v3/__https://pubmed.ncbi.nlm.nih.gov/35585145/__;!!LQC6Cpwp!tJe2o4OGOp-PlJPPIkjwkApL4dwknSYNVgp02MZgDy71toNCbJLQopxZnpLxsiPpqphNWEgINTLHsF1jWFn2Prd-RYZx$

Glycemic treatment deintensification practices in nursing home residents with type 2 diabetes

Nursing home (NH) residents with diabetes represent a large, growing population at high-risk for adverse events from glucose-lowering medications (GLMs). Studies in community dwelling older adults have shown that glycemic overtreatment is common and can cause significant harms. Recent studies have documented increased risk of mortality, severe hypoglycemia, cognitive impairment, and falls as potential negative consequences of overtreatment.

Approximately 1.3 million adults resided in an NH in 2016; an estimated 25%–34% of these NH residents have diabetes. Yet, despite the large and growing numbers of NH residents with diabetes, little is known about GLM prescribing and deprescribing practices in this population.

To dive into this mystery, NCIRE-supported investigators Sei Lee, MD, Michael Steinman, MD, and their colleagues conducted a cohort study from January 1, 2013, to December 31, 2019, among Veterans Affairs (VA) NH residents. Participants were VA NH residents age ≥65 with type 2 diabetes with a NH length of stay (LOS) ≥ 30 days and an HbA1c result during their NH stay. The study defined overtreatment as HbA1c <6.5 with any insulin use, and potential overtreatment as HbA1c <7.5 with any insulin use or HbA1c <6.5 on any glucose-lowering medication (GLM) other than metformin alone. The primary outcome was continued glycemic overtreatment without deintensification 14 days after HbA1c.

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