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One Mission, One Goal: Veterans Health

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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.

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Research News

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Olfactory and cognitive decrements in 1991 Gulf War veterans with gulf war illness/chronic multisymptom illness

A recent study conducted by NCIRE-supported Principal Investigator Linda Chao, PhD suggests losing one’s sense of smell could be a sign of r neurodegenerative issues.

Because olfactory deficit is a prodromal symptom of neurodegenerative diseases like Parkinson’s and Alzheimer’s disease, and because Chao’s research team previously reported suggestive evidence that deployed Gulf War (GW) Veterans may be at increased risk for Mild Cognitive Impairment (MCI) and dementia, the current study examined the relationship between olfactory and cognitive function in deployed GW Veterans.

Eighty deployed GW Veterans (mean age: 59.9, ±7.0; 4 female) were tested remotely with the University of Pennsylvania Smell Identification Test (UPSIT) and the Montreal Cognitive Assessment (MoCA). Veterans also completed self-report questionnaires about their health and deployment-related exposures and experiences.

The study, titled “Olfactory and cognitive decrements in 1991 Gulf War veterans with gulf war illness/chronic multisymptom illness” was published in the science journal Environmental Health.

Read more: https://ehjournal.biomedcentral.com/articles/10.1186/s12940-024-01058-2

 

Linda Chao, PhD is a Professor of Radiology & Biomedical Imaging and Psychiatry at the University of California, San Francisco. She is also a Research Biologist and Neuroscientist with the San Francisco VA Health Care System. Her scientific investigations primarily consist of conducting basic research using neuropsychological and imaging techniques to characterize how normal aging, neurodegenerative processes, stress, and exposure to neurotoxins affect the brain and cognition.

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Which older adults are at highest risk of prescribing cascades? A national study of the gabapentinoid–loop diuretic cascade

Prescribing cascades, or the treatment of an adverse drug reaction with another drug, are significant contributors to polypharmacy, where a patient takes multiple medications in day. However, little is known about which older adults are at the highest risk of experiencing prescribing cascades.

NCIRE-supported researchers Drs. Amy Byers, John Boscardin, and Michael Steinman were part of a research team that explored which older veterans are at the highest risk of the gabapentinoid (including gabapentin and pregabalin)–loop diuretic cascade, given the dramatic increase in gabapentinoid prescribing in recent years.

The research team used Veterans Affairs and Medicare claims data (2010–2019) and performed a prescription sequence symmetry analysis (PSSA) to assess loop diuretic initiation before and after gabapentinoid initiation among older veterans (≥66 years).

The study was published in the Journal of the American Geriatrics Society.

 

Learn More: https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18892

 

Amy Byers, PhD is a Professor of Psychiatry and Behavioral Health Sciences, and Professor of Medicine with the Division of Geriatrics at the University of California, San Francisco (UCSF). Dr. Byers is also a Research Career Scientist with the San Francisco VA Health Care System (SFVAHCS). Dr. Byers leads an independent program and oversees the Byers Lab, which focuses on determining the incidence, prevalence, risk factors, and outcomes of late-life mental health disorders and behaviors, with a focus on late-life suicide and neuropsychiatric disorders using large, epidemiologic, and administrative datasets.

W. John Boscardin, PhD is a biostatistician with a joint appointment as Professor of Medicine and Epidemiology & Biostatistics at UCSF. His primary roles with the Department of Medicine are as Director of the Statistical Laboratory in the UCSF Division of Geriatrics, co-leader (with Dr. Michael Steinman) of the UCSF Pepper Center Data and Analysis Core, and co-leader (with Dr. Amy Kelley of the Icahn School of Medicine at Mt. Sinai) of the Analytics Core for the UCSF/Mount Sinai DEVELOP AD Research Program Project.

Michael Steinman, MD is a national leader in identifying and improving the quality of medication prescribing in older adults, particularly those with multiple chronic conditions. Other research interests include improving care for older adults with multiple chronic conditions, and mentorship for junior investigators. Dr. Steinman is also involved in several local and national initiatives, including co-chair of the Beers Criteria Guideline of Potentially Inappropriate Medications for Older Adults.

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Ken Covinsky and Sei Lee presented at the Congress of Geriatrics and Gerontology in Brazil

NCIRE-supported Principal Investigators Ken Covinsky, MD, MPH, and Sei Lee, MD, MAS presented at the Congress of Geriatrics and Gerontology of Sao Paolo, Brazil Apr 4-6, 2024. The sessions were wide-ranging focusing on opportunities for international collaboration, ePrognosis and the central role of function in geriatrics.

Learn More: https://geriatrics.ucsf.edu/innovations/eprognosis

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Cognitive, physical, and sensory deficits that can affect everyday medication use among older adults: A national view

The challenges often experienced by those getting older can have an impact on medication management, says a recent article co-authored by NCIRE-supported PrincipaI Investigator Michael Steinman, MD titled “Cognitive, physical, and sensory deficits that can affect everyday medication use among older adults: A national view”.

Challenges in the domains of cognition (e.g., dementia, which may lead to issues with remembering medication schedules and dosages), physical ability (e.g., hand dexterity and strength, which may include difficulty opening pill bottles), and/or sensory ability (e.g., limited vision, which may present as problems reading medication labels) are associated with non-adherence, medication errors, and preventable medication-related hospital admissions.

The study, published in the Journal of the American Geriatrics Society, consisted of a cross-sectional investigation of a nationally representative sample group of 6,592 older adults aged 65 and over, who reported taking a prescription medication in the last month, from the 2015 National Health and Aging Trends Study (NHATS).

 

Learn more: https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18922

 

Michael Steinman, MD is a Professor of Medicine at the University of California, San Francisco, and is a national leader in identifying and improving the quality of medication prescribing in clinically complex older adults. He devotes most of his time to research, while also maintaining an active clinical practice in the geriatrics clinic and inpatient general medicine service at the San Francisco VA Health Care Center. Dr. Steinman's research program focuses on improving how medications are prescribed for older adults and is supported by grants from the National Institutes of Health and other funders. His research interests also include improving evaluation and care for older adults with multiple chronic conditions and he has a strong interest in mentorship and supporting career development for junior investigators.

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Dr. Raymond Swanson co-authored two studies that recently published studies exploring cofilactin rod formation and its impact on the brain

NCIRE-supported Principal Investigator Dr. Raymond Swanson along with  his research team recently co-authored two studies that explore cofilactin rod formation and its impact on the brain traumatized by instances of stroke and conditions such as multiple sclerosis, traumatic brain injury, and neurodegenerative disorders.

In the study “Cofilactin rod formation mediates inflammation-induced neurite degeneration”, Dr. Swanson and colleagues investigated the formation of cofilactin rods (CARs) and subsequent neurite loss in the brain. The research team discovered that even with mild inflammation, CARs strip away the neurites (the little arms of the neurons) leaving the neurons as isolated entities—such a loss is associated with functional impairment. Thus, a new degenerative pathway was discovered: inflammation caused immune cells to release superoxide, pulling cofilin and actin out of neurites and making CARs. Neurites died, and the disconnected brain malfunctioned.

In the related study “Bioenergetic and excitotoxic determinants of cofilactin rod formation”, Dr. Swanson and his team also looked into how the biochemical pathways driving CAR formation are engaged under ischemic conditions.

With both studies, scientists now have a better understanding of the pathways in which CARs are formed and the impact that has on the brain’s neurological structure. Armed with this information, therapies can be designed to interrupt inflammatory pathway. Stroke patients, for example, could be treated early on with anti-inflammatory agents to shield neurites from damage and preserve cognition.

 

Raymond Swanson, MD is a clinician-scientist with joint appointments in the University of California San Francisco Department of Neurology and the San Francisco Veterans Affairs Health Care System. His research explores bioenergetics and oxidative signaling in neurological disease. Dr. Swanson’s studies in the area of stroke aim to identify ways to mitigate the dendritic and axonal ischemic injury, and in particular injuries caused by neuronal NADPH oxidase and cofilin-actin rod formation.

 

Read More:

  1. “Cofilactin rod formation mediates inflammation-induced neurite degeneration”. Cell Reports, Volume 43, Issue 3.

https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00242-0

   2. "Bioenergetic and excitotoxic determinants of cofilactin             rod formation”. Journal of Neurochemistry.

https://onlinelibrary.wiley.com/doi/10.1111/jnc.16065

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Blood Markers show neural consequences of LongCOVID-19

In a co-authored study published in the science journal Cells, NCIRE-supported Principal Investigators Drs. Lynn Pulliam and Judith Ford collaborated with colleagues to investigate the impact of Long-COVID-19 (LongC) on the nervous system.

To search for neurological markers of LongC, the research team investigated the soluble biomolecules present in the plasma and the proteins associated with plasma neuronal-enriched extracellular vesicles (nEVs) in 33 LongC patients with neurological impairment (nLongC), 12 COVID-19 survivors without any LongC symptoms (Cov), and 28 pre-COVID-19 healthy controls (HC). COVID-19 positive participants were infected between 2020 and 2022, not hospitalized, and were vaccinated or unvaccinated before infection. Interleukin-1-beta (IL-1β) was significantly increased in both nLongC and Cov and Interleukin-8 (IL-8) was elevated in only nLongC. Both brain-derived neurotrophic factor and cortisol were significantly elevated in nLongC and Cov compared to HC. Additionally, nEVs from people with nLongC had significantly elevated protein markers of neuronal dysfunction, including amyloid beta 42, pTau181 and transactive response DNA binding protein 43 kDa (TDP-43).

The study showed chronic peripheral inflammation with increased stress after COVID-19 infection. Additionally, differentially expressed nEV neurodegenerative proteins were identified in people recovering from COVID-19 regardless of persistent symptoms:  differentially expressed peripheral markers of inflammation and stress after SARS-CoV-2 infection between healthy pre-pandemic controls, people recovered from COVID-19 and neuroLongCOVID-19 subjects.

Judith Ford, PhD is Professor of Psychiatry at the University of California San Francisco (UCSF) Weill Institute for Neurosciences and Senior Career Research Scientist, Mental Health Service at the San Francisco VA Health Care System (SFVAHCS). She co-directs the Brain Imaging and Electroencephalography (EEG) Laboratory at UCSF, where she is using human electrophysiological methods to understand failures of a basic neurophysiological mechanism in patients with schizophrenia.

Lynn Pulliam, MS, PhD is the Chief of Microbiology at the SFVAHCS and Professor of Laboratory Medicine and Medicine at UCSF. Dr. Pulliam’s laboratory was the first to show that blood monocytes (white blood cells) from individuals with HIV release toxins that kill or damage neural cells. Her lab is interested in finding blood monocyte biomarkers to identify chronic activation, which puts subjects at risk for different co-morbid pathologies, as well as determine how the immune system affects cognition.

 

Read More:

https://www.mdpi.com/2073-4409/13/6/478

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