Research News

Congratulations to Dr. Bruce Ovbiagele for his recent awards!
October 22, 2022
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.

The Polygenic Risk Score Knowledge Base offers a centralized online repository for calculating and contextualizing polygenic risk scores
October 17, 2022
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
September 16, 2022
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/

Rebecca Sudore receives GeriPal Mentor of the Year Award!
August 26, 2022
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
August 24, 2022
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
August 22, 2022
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
August 19, 2022
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.

Dr. Li-Wen Huang named 2022 Grunfeld Scholar
August 8, 2022
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
June 21, 2022
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.

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
June 17, 2022
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.
June 16, 2022
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
June 13, 2022
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!
May 26, 2022
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

Glycemic treatment deintensification practices in nursing home residents with type 2 diabetes
May 12, 2022
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.

Sliding scale insulin use in a national cohort study of nursing home residents with type 2 diabetes
May 11, 2022
NCIRE scientist Sei Lee, MD co-published a study that sought to determine the prevalence of sliding scale insulin (SSI) use and identify factors associated with stopping SSI or transitioning to another short-acting insulin regimen, in light of health guidelines that discourage SSI use after the first week of a nursing home (NH) admission.
The observational study gathered data from October 1, 2013, to June 30, 2017, of non-hospice Veterans Affairs NH residents with type 2 diabetes and an NH admission over 1 week and compared the weekly prevalence of SSI versus two other short-acting insulin regimens – fixed dose insulin (FDI) or correction dose insulin (CDI, defined as variable SSI given alongside fixed doses of insulin) – from week 2 to week 12 of admission.
Among those on SSI in week 2, the study examined factors associated with stopping SSI or transitioning to other regimens by week 5. Factors included demographics (e.g., age, sex, race/ethnicity), frailty-related factors (e.g., comorbidities, cognitive impairment, functional impairment), and diabetes-related factors (e.g., HbA1c, long-acting insulin use, hyperglycemia, and hypoglycemia).
In week 2, 21% of the cohort was on SSI, 8% was on FDI, and 7% was on CDI. SSI was the most common regimen in frail subgroups (e.g., 18% of our cohort with moderate–severe cognitive impairment was on SSI vs 5% on FDI and 4% on CDI). SSI prevalence decreased steadily from 21% to 16% at week 12 (p for linear trend <0.001), mostly through stopping SSI. Diabetes-related factors (e.g., hyperglycemia) were more strongly associated with continuing SSI or transitioning to a non-SSI short-acting insulin regimen than frailty-related factors.
The study was published in the Journal of the American Geriatrics Society.

Association of Race and Ethnicity with Incidence of Dementia Among Older Adults
May 10, 2022
The racial and ethnic diversity of the U.S., including among patients receiving their care at the Veterans Health Administration (VHA), is increasing. Dementia is a significant public health challenge and may have greater incidence among older adults from underrepresented racial and ethnic minority groups.
Studies examining racial and ethnic disparities in dementia incidence in the U.S. have consistently reported higher rates of dementia for Black adults. Hispanic older adults are less well studied, but also have greater dementia incidence than White older adults. Much less is known about dementia incidence for American Indian or Alaska Native or for Asian individuals.
NCIRE Board Director Kristine Yaffe, MD, and fellow NCIRE-supported investigators John Boscardin, PhD, and Deborah Barnes, PhD, MPH co-published a study that sought to answer: Is there a difference in incidence of dementia by race and ethnicity among enrollees in the U.S. VHA?
This retrospective cohort study sampled 1,869,090 older adults receiving care at VHA medical centers, the largest integrated health care system in the US. Differences in incidence rates by geographical region across the US were also examined. The sample group were aged 55 years or older and with data evaluated from October 1, 1999, to September 30, 2019 (the date of final follow-up).
The study found that among older adults who received care at VHA medical centers, there were significant differences in dementia incidence based on race and ethnicity. Further research is needed to understand the mechanisms responsible for these differences.
The study was published in the JAMA Network.

Surrogate Decision Makers Need Better Preparation for Their Role: Advice from Experienced Surrogates
May 9, 2022
Surrogate decision makers are required to make difficult end-of-life decisions with little preparation. Little is known about what surrogates may need to adequately prepare for their role, and few resources exist to prepare them.
NCIRE-supported scientists Deborah Barnes, PhD and Rebecca Sudore, MD, with a team of investigators, explored experiences and advice from surrogates about how best to prepare for the surrogate role. Using a semi-structured focus group model, the study recruited 69 participants through convenience sampling in San Francisco area hospitals, cancer support groups, and community centers for 13 focus groups. Surrogates were included if they were 18 years of age or older and reported having made medical decisions for others.
Experienced surrogate decision makers emphasized the importance of advance care planning (ACP) and advised that surrogates need their own preparation to initiate ACP conversations, learn patients' values, advocate for patients, and make informed surrogate decisions. Future interventions should address these preparation topics to ease surrogate burden and decrease disparities in surrogate decision making.
The study was published in the Journal of Palliative Medicine.

Life expectancy for community-dwelling persons with dementia and severe disability
April 27, 2022
For people with dementia or a severe disability having a clear understanding of their prognosis can help them, their care partners, and clinicians anticipate and plan for future social, financial, functional, and clinical needs.
While prior work around life expectancy and needs of persons with dementia have focused on either overall life expectancy at the time of diagnosis or on end-of-life estimates in nursing home settings, there have been no studies examining life expectancy in community-dwelling persons with dementia, even though the majority of care partners and persons with dementia want to remain at home.
In a first of its kind study, NCIRE Board Director Kristine Yaffe, MD, and fellow NCIRE-supported investigator John Boscardin, PhD, and their colleagues found that among the 842 community-dwelling persons with dementia and severe disability evaluated, the median life expectancy is 1.7 years; one quarter died within 7 months.
The paper was published in the Journal of the American Geriatrics Society.

Association of Vitamin D Status and COVID-19-Related Hospitalization and Mortality
April 20, 2022
The relationship between vitamin D status and COVID-19-related clinical outcomes is controversial. Prior studies have been conducted in smaller, single-site, or homogeneous populations limiting adjustments for social determinants of health (race/ethnicity and poverty) common to both vitamin D deficiency and COVID-19 outcomes.
NCIRE Board Director Carl Grunfeld, MD, PhD, and fellow NCIRE-supported investigators, Karen Seal, MD and Daniel Bikle, MD, PhD, co-authored a study that evaluates the dose-response relationship between continuous 25(OH)D and risk for COVID-19-related hospitalization and mortality after adjusting for covariates associated with both vitamin D deficiency and COVID-19 outcomes.
The retrospective cohort study investigated 4,599 Veteran patients receiving care in U.S. Department of Veteran Affairs health care facilities with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and a blood 25(OH)D test between February 20, 2020, and November 8, 2020, followed for up to 60 days.

Screening and enrollment of underrepresented ethnocultural and educational populations in the Alzheimer's Disease Neuroimaging Initiative (ADNI)
April 1, 2022
According to the Alzheimer’s Association, older Black Americans are about twice as likely to have Alzheimer’s or other dementias as whites; older Hispanics are one-and-a-half times as likely to have these disorders as whites. By 2030, nearly 40 percent of all Americans living with Alzheimer’s will be Black or Latino, according to UsAgainstAlzheimer’s, an organization founded in 2010 to diversify Alzheimer’s research.
With this is mind, NCIRE-supported Investigator Michael Weiner, MD and his cohorts conducted an analysis of the ethnocultural and socioeconomic composition of Alzheimer's Disease Neuroimaging Initiative (ADNI) participants to assess the generalizability of ADNI data to diverse populations.
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.
In the analysis, ADNI data collected between October 2004 and November 2020 were used to determine ethnocultural and educational composition of the sample and differences in the following metrics: screening, screen fails, enrollment, biomarkers.
Of the 3739 screened individuals, 11 percent identified as being from ethnoculturally underrepresented populations (e.g., Black, Latinx) and 16 percent had less than 12 years of education. Of the 2286 enrolled participants, 11 percent identified as ethnoculturally underrepresented individuals and 15 percent had less than 12 years of education. This participation is considerably lower than US Census data for adults 60+ (ethnoculturally underrepresented populations: 25 percent; less than 12 years of education: 4 percent). Individuals with less than 12 years of education failed screening at a higher rate.

A rare case of axillary keratoacanthoma arising in hidradenitis suppurativa
March 31, 2022
Keratoacanthoma (KA), a cutaneous, often spontaneously regressing tumor characteristically presenting as an umbilicated nodule with a central keratin plug, occurs most frequently in lightly pigmented individuals with sun damage. NCIRE-supported Investigator Maria Wei, MD, PhD co-published a study that reports an unusual case of KA with a large pedunculated morphology, diagnosed in an African American man, that arose in hidradenitis suppurativa (HS), a relapsing inflammatory skin disease affecting hair follicles in intertriginous areas.

Thomas Neylan, MD, 2021 Robert S. Laufer Memorial Award recipient
March 30, 2022
The International Society for Traumatic Stress Studies honored NCIRE-supported Investigator Thomas Neylan, MD with its 2021 Robert S. Laufer Memorial Award.
This award is given to an individual or group who has made an outstanding contribution to research in the field of traumatic stress. Robert S. Laufer, PhD, was a sociologist who made early and important contributions to the field of traumatic stress and PTSD through his research on the effects of war experiences on Vietnam combat veterans. Laufer was Professor of Sociology at Brooklyn College of the City University of New York and an author of the groundbreaking study of returning veterans, entitled Legacies of Vietnam: Comparative Adjustment of Veterans and Their Peers, published in 1981, with Arthur Egendorf, Ellen Frey-Wouters, and others.
Laufer and colleagues expanded the concept of combat exposure to include multiple dimensions. In particular, he focused on witnessing or participating in abusive violence, an important new focus for a guerilla war where there were no front lines, and where enemy combatants and civilians were often difficult to distinguish. He found that abusive violence followed from more extreme exposure to combat, and was associated with distinctive psychological and behavioral outcomes, including different aspects of PTSD. Laufer died prematurely of cancer in 1989 at the age of 47. This award is made in his memory.

Daniel Mathalon, PhD honored with Lifetime Achievement Award
March 29, 2022
NCIRE-supported Investigator Daniel Mathalon, PhD was one of five psychological and brain sciences alumni honored by the University of Indiana at its Department of Psychological and Brain Sciences’ 2021 Alumni Recognition Day back in October 2021.
Dr. Mathalon received the department’s Lifetime Achievement Award for his prestigious work in the field of psychiatry.
The department, in the IU Bloomington College of Arts and Sciences, has acknowledged outstanding graduates of its bachelor’s and Ph.D. programs with a series of awards since 2013, the year of the department’s 125th anniversary.
Dr. Mathalon is the Deputy Vice Chair for Research at the San Francisco VA Health Care System, and professor with the Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences at University of California, San Francisco.

Deep learning for Alzheimer's disease: Mapping large-scale histological tau protein for neuroimaging biomarker validation
March 28, 2022
Definite diagnosis of Alzheimer’s disease is now determined at autopsy when the abnormal spread in the brain of proteins – including “tau” – are evident. But researchers at the UCSF Center for Intelligent Imaging (ci2), including NCIRE-supported Investigator Duygu Tosun-Turgut, PhD, suggest that “in vivo tau PET imaging” may be a game changer by visualizing tau deposition in living people.
Their study in the March issue of NeuroImage (https://www.sciencedirect.com/science/article/pii/S1053811921010570) opens avenues for thorough and systematic validation of new neuroimaging tracers and expediting their approval for clinical use.
"This work outlines an end-to-end deep learning-powered pipeline to facilitate dense quantification of whole-brain tau inclusions observed at autopsy in perfect alignment with in vivo neuroimaging, which will allow directly linking imaging measures to ground-truth neuropathological inclusions at autopsy," said Dr. Tosun.

Moral injury increases Veterans’ suicide risk
February 16, 2022
Moral injury during military service increases suicide risk in both men and women, according to a study by NCIRE-supported Investigator Shira Maguen, PhD. The study of more than 14,000 Veterans found that men who experienced moral injury were 50 percent more likely to attempt suicide during their service and twice as likely to do so after leaving the military, compared with those without moral injury. Men who felt betrayed were nearly twice as likely than those without these feelings to attempt suicide during service, but no more likely after service.
Women who experienced betrayal were over 50 percent more likely to attempt suicide both during and after service. Perpetrating a morally injurious act did not increase the suicide risk of women Veterans.
The study, published in Psychological Medicine, suggests that moral injury assessment should take gender difference into account.

New study reevaluates Annual Growth Rate of Nonsyndromic Ascending Thoracic Aortic Aneurysms
February 7, 2022
While previous studies of nonsyndromic ascending thoracic aortic aneurysms (aTAAs) reported that the typical aTAA growth rate was approximately 0.6 mm/year, there are few studies that have measured the annual growth of aTAAs using computed tomography (CT) imaging. NCIRE Board Director Michael Hope, MD, and NCIRE-supported Investigator Elaine Tseng, MD, FACS, co-published a study that reevaluates the annual growth rate of nonsyndromic aTAAs that do not meet criteria for surgical repair in Veterans in the contemporary era, using modern CT imaging suitable for highly accurate and reproducible aneurysm measurement.

Connection found between ACE inhibiters and reduced risks associated with COVID-19 infections
February 3, 2022
Past studies have shown that SARS-CoV-2 (the virus that leads to COVID-19 infections) enters cells using the Angiotensin-converting enzyme 2 (ACE2) receptors.
But what happens in patients who are taking angiotensin receptor blockers, metformin, ACE inhibiters, and similar medication?
In the study titled “Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study”, investigators found that such medications have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury.
The study was co-published by NCIRE-supported Investigator, Arthur Wallace, MD and appeared in the peer-reviewed British Medical Journal.

Anxiety and PTSD linked to increased myelin in brain’s gray matter
January 11, 2022
We all respond differently to traumatic stressors, but what is the biological reason behind our various behavioral reactions to stress? Recent studies have shown that stress influences the plasticity of oligodendrocytes and the myelin they produce, demonstrating a mechanism by which trauma induces abnormal structural and functional changes in the adult brain.
An oligodendrocyte is a type of large glial cell found in the central nervous system that assembles myelin, a multilayered sheath of membrane that wraps around the axonal segments between nerve cells, aiding in faster communication between cells.
Taking a translational approach to test the hypothesis that gray matter oligodendrocytes contribute to traumatic-stress-induced behavioral variation, NCIRE-supported Investigators Linda Chao, PhD, and Thomas Neylan, MD, co-published a study in the peer-reviewed medical journal Translational Psychiatry linking anxiety and Post-traumatic Stress Disorder (PTSD) to increased myelin in brain’s gray matter.
Titled “Regional gray matter oligodendrocyte- and myelin-related measures are associated with differential susceptibility to stress-induced behavior in rats and humans”, the aim of this study was to determine the relationship between oligodendrocytes and the behavioral outcomes of trauma.
Conducting brain MRI scans of 38 Veterans — half with PTSD, half without — investigators found an increase in myelination in the gray matter of those with PTSD compared to that seen in the brains of those not suffering from PTSD.

Roam Robotics launches partnership with NCIRE and the San Francisco VA Health Care System to study the impact of its robotic wearable on the Veteran population
December 7, 2021
Roam Robotics, a company making innovations in the expansion of human mobility with wearable robotics, announced today that the Northern California Institute for Research and Education (NCIRE) and the San Francisco VA Health Care System (SFVAHCS) has begun enrolling patients to study the impact of Ascend, a first-of-its-kind smart brace, on the Veteran population.
Ascend, from Roam Robotics, is a smart knee orthosis designed to provide relief from knee pain and intuitively support everyday mobility.
Ascend is the first wearable robotic device to show usefulness in everyday life for people suffering from knee joint pain who want to regain independence and live more active lifestyles. A previous clinical study of knee osteoarthritis participants demonstrated an average of 46 percent pain reduction, and 67 percent exhibited functional improvement when using the device. Ascend is also registered with the FDA as a Class I medical device.

Study Finds Significant COVID-19 Vaccine Effectiveness Decline Amongst US Veterans
November 4, 2021
In the first study of its kind of more than 780,000 US Veterans, NCIRE-supported Investigator, Arthur Wallace, MD, and cohorts found that protection against any COVID-19 infection declined for all vaccine types, with overall vaccine protection declining from 87.9% in February to 48.1% by October 2021. The novel study was co-published in Science Magazine.

Investigating the Gene-Environment Interactions Related to Parkinson’s Disease Susceptibility
October 20, 2021
Parkinson’s disease (PD) is a neurodegenerative disease that progresses over time as small clusters of dopamine‐producing brain cells deteriorate, causing motor issues such as tremors, loss of coordination, and difficulty speaking. The Parkinson’s Foundation states that approximately one million Americans currently living with PD. Although the exact cause of disease onset is unknown, it is thought that a combination of genetic and environmental factors, as well as the interaction between them, are contributors. Through a Neurotoxin Exposure Treatment Parkinson’s Program (NETP) Fiscal Year 2019 Investigator‐Initiated Research Award, NCIRE-supported Investigators, Drs. Samuel Goldman and Raymond Swanson, aim to uncover the link between genetic and environmental factors that may contribute to the risk for PD.

Dr. Bruce Ovbiagele elected to the National Academy of Medicine
October 18, 2021
NCIRE-supported scientist and Board Member Dr. Bruce Ovbiagele has been elected as a new member of the prestigious National Academy of Medicine, as announced at its annual meeting held on October 18, 2021.
“I am, and have always been, committed to discovering new and innovative ways to ensure that health and wellness are not dependent on one’s race, ethnicity, geographic, or socioeconomic status,” said Dr. Ovbiagele. “This recognition by the National Academy of Medicine is a tremendous privilege and a meaningful validation of the efforts of my team to address health disparities here and abroad.”
New members are elected by current members of the Academy through a rigorous selection process that considers only the most exceptional individuals who have made major contributions to the advancement of the medical sciences, health care, and public health.
Dr. Ovbiagele was selected for his research focusing on the health of vulnerable populations (racial and ethnic minorities, the uninsured, rural dwellers, and military veterans) in the United States and Africa.
NCIRE congratulates Dr. Ovbiagele on his election to the National Academy of Medicine! We are proud and appreciative of his vital and ground-breaking work on behalf of often-overlooked and underserved communities both here and abroad.

Dr. Kenneth E. Covinsky co-publishes in Journal of the American Geriatrics Society
October 14, 2021
Alzheimer's disease and other dementias are progressive and terminal conditions that create immeasurable suffering for those it afflicts and their loved ones. Though the FDA recently approved aducanumab (Aduhelm, Biogen) for the treatment of Alzheimer's disease, its less-than-desirable clinical effectiveness and high price tag ($50,000 annual cost to patients) is causing much concern in the research community. NCIRE-supported scientist Dr. Kenneth E. Covinsky co-published an article with Drs. Lauren Hunt and Krista Harrison in the Journal of the American Geriatrics Society entitled “Instead of Wasting Money on Aducanumab, Pay for Programs Proven to Help People Living with Dementia”.

Dr. Louise Walter co-publishes study in the Journal of the American Geriatrics Society
October 5, 2021
Maintenance of function during cancer treatment is important to older adults; yet little was known about the characteristics associated with pretreatment life-space mobility and changes during non-small cell lung cancer (NSCLC) treatment. NCIRE-supported scientist and Board Member Dr. Louise Walter, with colleagues Drs. Melisa Wong and Alex Smith, conducted a mixed methods cohort study of adults 65 and older with advanced NSCLC over the course of six months to examine patient experience of life-space change during treatment.
Their published study can be found in the Journal of the American Geriatrics Society.

Glycoprotein associated with cardiac valve damage in animal models of infective endocarditis
September 21, 2021
Some oral bacteria colonize on tooth surfaces, but they can seep into the bloodstream and settle inside the heart’s chambers and valves. They may even cause infective endocarditis (IE), which can lead to stroke and heart failure. In a study in the journal Glycobiology, SFVAHCS researcher Dr. Barbara Bensing identifies a group of proteins, expressed by oral bacteria, and how they help the organisms bind and colonize on cardiac valve surfaces.
She found significantly higher levels of a particular glycoprotein, lubricin, in laboratory animals with damaged or infected valves, as compared to healthy animals. Presence of this protein could serve as a biomarker for endocardial injury or infection, suggests the study.
Dr. Bensing, was formerly a postdoctoral fellow in the laboratory of NCIRE-supported scientist Paul Sullam, MD, who was a co-author of the study.