Geriatrics Commons^™

Ongoing Study Of The Association Of Apoe Gene Polymorphisms With Cognitive Impairment In The Rio Grande Valley Hispanic Population, Jaime Miguel L. Saveron, Daniela Gamez, Chun Xu

Research Symposium

Background: Alzheimer's disease (AD), a prevalent neurodegenerative disorder, exhibits a significant genetic component. In addition, mild cognitive impairment (MCI) is a key risk factor for AD. While certain demographic factors and genetic variants associated with AD and cognitive impairment have been identified in non-Hispanic populations, limited research exists on this subject within the Hispanic population, particularly in the Rio Grande Valley. This study aims to investigate the relationship between the APOE gene, specifically its ε4 allele, and cognitive impairment in the Hispanic population of the Rio Grande Valley.

Methods: A total of 269 Hispanic subjects, aged 60 and above, with …

In Sickness And In Health-Type I Interferon And The Brain, Wei Cao

Journal Articles

Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I's effects on brain aging, Alzheimer's disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms …

Assessment Of Deficits In Specific Cognitive Domains In Older Adults Living With Hiv., Andrea Reyes-Vega, Harideep Samanapally, Rishikesh Rijal, Stephen P. Furmanek, Christopher B. Shields, Brandon C. Dennis, Smita Ghare, Shirish Barve

Faculty Scholarship

A significant proportion of people living with HIV (PLWH) have cognitive impairment. Moreover, approximately 70% of PLWH in the United States will be ≥50 years old by 2030, raising concerns of a higher incidence of dementia as they age. Accordingly, there is a clinical need to monitor their cognitive status. The aim of this study was to delineate specific cognition areas impacted in OALWH with a clinical diagnosis of neurocognitive impairment. We used a comprehensive set of tests (paper and NIH Toolbox Cognition Battery), to assess different cognitive domains in a total of 25 OALWH ≥ 50 years. 64% were …

The Pharmacological Deprescription In Elderly Patients, Chelsey Ali, Daniel Huang, Charlene Tugwete, Stefano Del Canale, Vittorio Maio

College of Population Health Faculty Papers

No abstract provided.

Meaningful Engagement Of Patients And Families In A Complex Trial Of Advance Care Planning In Primary Care, Angela K. Combe, Deborah L. Dokken, Mary M. Minniti, Annette M. Totten

Patient Experience Journal

Engagement of Patient and Family Advisors (PFAs) is increasingly recommended as best practice in research. During the design and conduct of a large trial of advance care planning (ACP) in primary care, we expanded on the funder’s (Patient-Centered Outcomes Research Institute®) requirement for an engagement plan and sought to develop an innovative approach to fostering and sustaining meaningful engagement of PFAs throughout all phases of the trial. Structures were developed that integrated PFAs into planning and provided the foundation for their ongoing participation. A continuous quality improvement approach became the framework for ongoing engagement. This involved setting goals; collecting data …

The Impact Of Access To Oral Health Care On Inadequate Oral Health And Multimorbidity, Luis Limo

Electronic Thesis and Dissertation Repository

The connection between oral health and other non-communicable chronic conditions—commonly referred in the dental literature as the oral-systemic health connection—emphasizes the role of oral health care on both oral diseases and chronic conditions, particularly in vulnerable populations like the elderly. This thesis comprises 2 studies: the first is a systematic review on the impact of oral health care interventions, as an indicator of access to oral health care, on chronic conditions of which their co-existence would result in multimorbidity; the second study is a cross-sectional investigation of the associations between oral health, access to oral health care, and multimorbidity among …

Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques.

Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients.

Methods: We selected Western blotting technique to study …

A 5-Year Clinical Course Of Phenocopy Syndrome Of Behavioral Variant Frontotemporal Dementia: Case Report And Literature Review, Joseph Melillo, Keyur Patel, Christian White

Rowan-Virtua Research Day

Frontotemporal dementia is a neurocognitive disease which affects language, behavior, or executive functioning. This disease includes a spectrum of presentations which includes multiple variants. The phenocopy syndrome of behavioral variant frontotemporal dementia is one which mimics the behavioral variant of frontotemporal dementia. Patients with this condition show a decline in personality, social conduct and cognitive ability but often display no signs of neurological imaging and exhibit slow progression. This case focuses on a now 70-year-old male who has shown signs of behavioral changes with a slowly progressive clinical course and minimal findings on PET scan, but moderate changes seen on …

Rna Editing Of Microtubule-Associated Protein Tau Circular Rnas Promotes Their Translation And Tau Tangle Formation, Justin Ralph Welden, Giorgi Margvelani, Karol Andrea Arizaca Maquera, Bhavani Gudlavalleti, Sandra C. Miranda Sardón, Alexandre Rosa Campos, Noémie Robil, Daniel C. Lee, Alvaro G. Hernandez, Wang-Xia Wang, Jing Di, Pierre De La Grange, Peter T. Nelson, Stefan Stamm

Sanders-Brown Center on Aging Faculty Publications

Aggregation of the microtubule-associated protein tau characterizes tauopathies, including Alzheimer’s disease and frontotemporal lobar degeneration (FTLD-Tau). Gene expression regulation of tau is complex and incompletely understood. Here we report that the human tau gene (MAPT) generates two circular RNAs (circRNAs) through backsplicing of exon 12 to either exon 7 (12→7 circRNA) or exon 10 (12→10 circRNA). Both circRNAs lack stop codons. The 12→7 circRNA contains one start codon and is translated in a rolling circle, generating a protein consisting of multimers of the microtubule-binding repeats R1–R4. For the 12→10 circRNA, a start codon can be introduced by two …

Genetic Expression Changes And Pathologic Findings Associated With Hyperhomocysteinemia In Human Autopsy Brain Tissue, Erica M. Weekman, Zachary Winder, Colin B. Rogers, Erin L. Abner, Tiffany L. Sudduth, Ela Patel, Adam J. Dugan, Shuling X. Fister, Brandi Wasek, Peter T. Nelson, Gregory A. Jicha, Teodoro Bottiglieri, David W. Fardo, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Introduction: Vascular contributions to cognitive impairment and dementia (VCID) are a leading cause of dementia. An underappreciated, modifiable risk factor for VCID is hyperhomocysteinemia (HHcy), defined by elevated levels of plasma homocysteine, most often due to impaired B vitamin absorption in aged persons. Studies aimed at identifying neuropathologic features and gene expression profiles associated with HHcy have been lacking.

Methods: A subset of research volunteers from the University of Kentucky Alzheimer’s Disease Research Center longitudinal cohort came to autopsy and had ante mortem plasma homocysteine levels available. Brain tissue and blood plasma drawn closest to death were used to measure …

Apoe Genetics Influence Murine Gut Microbiome, Diana J. Zajac, Stefan J. Green, Lance A. Johnson, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we evaluated effects of APOE heterozygosity and tested whether these overall results extended to mice maintained under ideal conditions for microbiome analyses. To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, homozygous APOE3 mice were crossed to homozygous APOE2 or homozygous APOE4 mice prior to the study, and the resulting …

Single Low-Dose Targeted Bevacizumab Infusion In Adult Patients With Steroid-Refractory Radiation Necrosis Of The Brain: A Phase Ii Open-Label Prospective Clinical Trial, Shervin R. Dashti, Robert J. Kadner, Bradley S. Folley, Jason P. Sheehan, Dong Y. Han, Richard J. Kryscio, Mary B. Carter, Lisa B. E. Shields, Brian M. Plato, Renato V. La Rocca, Aaron C. Spalding, Tom L. Yao, Justin F. Fraser

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE There is an unmet need for safe and rapidly effective therapies for refractory brain radiation necrosis (RN). The aim of this prospective single-arm phase II trial was to evaluate the safety and efficacy of a single low-dose targeted bevacizumab infusion after blood-brain barrier disruption (BBBD) in adult patients with steroid-refractory brain RN.

METHODS Ten adults with steroid-refractory, imaging-confirmed brain RN were enrolled between November 2016 and January 2018 and followed for 12 months after treatment. Bevacizumab 2.5 mg/kg was administered as a one-time targeted intra-arterial infusion immediately after BBBD. Primary outcomes included safety and > 25% decrease in lesion volume. …

The Association Of Gabapentin Initiation And Neurocognitive Changes In Older Adults With Normal Cognition, Gyeon Oh, Daniela Claudia Moga, David W. Fardo, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

Background: Gabapentin is increasingly prescribed to older adults, which raises concerns about its potential to cause neurocognitive changes. Therefore, we aimed to examine the association of gabapentin use with neurocognitive changes (i.e., cognitive decline, functional status decline, and motor function change) in older adults.

Methods: We conducted a retrospective cohort study using the National Alzheimer’s Coordinating Center Uniform Data Set (UDS; September 2005-March 2021 data freeze). From the eligible sample (≥age 65 years), we identified cognitively normal new-users of gabapentin and the visit they initiated gabapentin (i.e., index visit). Initiators were matched to randomly selected nonusers on year …

Deep Learning Algorithm Reveals Probabilities Of Stage-Specific Time To Conversion In Individuals With Neurodegenerative Disease Late, Xinxing Wu, Chong Peng, Peter T. Nelson, Qiang Cheng

Sanders-Brown Center on Aging Faculty Publications

Introduction: Limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) is a recently defined neurodegenerative disease. Currently, there is no effective way to make a prognosis of time to stage-specific future conversions at an individual level.

Methods: After using the Kaplan–Meier estimation and log-rank test to confirm the heterogeneity of LATE progression, we developed a deep learning–based approach to assess the stage-specific probabilities of time to LATE conversions for different subjects.

Results: Our approach could accurately estimate the disease incidence and transition to next stages: the concordance index was at least 82% and the integrated Brier score …

Examining The Effects Of Formal Education Level On The Montreal Cognitive Assessment, Renee S. White, Justin M. Barber, Jordan P. Harp, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Background: Brief, global assessments such as the Montreal Cognitive Assessment (MoCA) are widely used in primary care for assessing cognition in older adults. Like other neuropsychological instruments, lower formal education can influence MoCA interpretation.

Methods: Data from 2 large studies of cognitive aging were used—Alzheimer’s Disease Neuroimaging Initiative (ADNI) and National Alzheimer’s Coordinating Center (NACC). Both use comprehensive examinations to determine cognitive status and have brain amyloid status for many participants. Mixed models were used to account for random variation due to data source.

Results: Cognitively intact participants with lower education (≤12 years) were more likely than …

Multiple Gene Variants Linked To Alzheimer's-Type Clinical Dementia Via Gwas Are Also Associated With Non-Alzheimer's Neuropathologic Entities, Yuriko Katsumata, Lincoln M. P. Shade, Timothy J. Hohman, Julie A. Schneider, David A. Bennett, Jose M. Farfel, Walter A. Kukull, David W. Fardo, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

The classic pathologic hallmarks of Alzheimer’s disease (AD) are amyloid plaques and neurofibrillary tangles (AD neuropathologic changes, or ADNC). However, brains from individuals clinically diagnosed with “AD-type” (amnestic) dementia usually harbor heterogeneous neuropathologies in addition to, or other than, ADNC. We hypothesized that some AD-type dementia associated genetic single nucleotide variants (SNVs) identified from large genomewide association studies (GWAS) were associated with non-ADNC neuropathologies. To test this hypothesis, we analyzed data from multiple studies with available genotype and neuropathologic phenotype information. Clinical AD/dementia risk alleles of interest were derived from the very large GWAS by Bellenguez et al. (2022) who …

The Intersection Between Toxicology And Aging Research: A Toxic Aging Coin Perspective., John P. Wise Jr.

Faculty Scholarship

We are imminently faced with the challenges of an increasingly aging population and longer lifespans due to improved health care. Concomitantly, we are faced with ubiquitous environmental pollution linked with various health effects and age-related diseases which contribute to increased morbidity with age. Geriatric populations are rarely considered in the development of environmental regulations or in toxicology research. Today, life expectancy is often into one’s 80s or beyond, which means multiple decades living as a geriatric individual. Hence, adverse health effects and late-onset diseases might be due to environmental exposures as a geriatric, and we currently have no way of …

Role Of Sympathetic Pathway In Light-Phase Time-Restricted Feeding-Induced Blood Pressure Circadian Rhythm Alteration, Tianfei Hou, Aaron Chacon, Wen Su, Yuriko Katsumata, Zhenheng Guo, Ming Gong

Sanders-Brown Center on Aging Faculty Publications

Disruption of blood pressure (BP) circadian rhythm, independent of hypertension, is emerging as an index for future target organ damage and is associated with a higher risk of cardiovascular events. Previous studies showed that changing food availability time alters BP rhythm in several mammalian species. However, the underlying mechanisms remain largely unknown. To address this, the current study specifically investigates (1) the relationship between rhythms of food intake and BP in wild-type mice; (2) effects of light-phase time-restricted feeding (TRF, food only available during light-phase) on BP circadian rhythm in wild-type and diabetic db/db mice; (3) the roles of the …

The Trend Of Disruption In The Functional Brain Network Topology Of Alzheimer’S Disease, Alireza Fathian, Yousef Jamali, Mohammad Reza Raoufy, The Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Norbert Schuf, Howard J. Rosen, Bruce L. Miller, Thomas Neylan, Jacqueline Hayess, Shannon Finley, Paul Aisen, Zaven Khachaturian, Ronald G. Thomas, Charles D. Smith, Gregory A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain’s functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimer’s disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and …

Patients’ Attitudes Toward Deprescribing And Their Experiences Communicating With Clinicians And Pharmacists, Kaylee Marie Lukacena, James W. Keck, Patricia R. Freeman, Nancy Grant Harrington, Mark Huffmyer, Daniela C. Moga

Sanders-Brown Center on Aging Faculty Publications

Purpose: Developing effective deprescribing interventions relies on understanding attitudes, beliefs, and communication challenges of those involved in the deprescribing decision-making process, including the patient, the primary care clinician, and the pharmacist. The objective of this study was to assess patients’ beliefs and attitudes and identify facilitators of and barriers to deprescribing.

Methods: As part of a larger study, we recruited patients ⩾18years of age taking ⩾3 chronic medications. Participants were recruited from retail pharmacies associated with the University of Kentucky HealthCare system. They completed an electronic survey that included demographic information, questions about communication with their primary care clinician and …

Characterization And Comparison Of Human Glioblastoma Models, Julia A. Schulz, Louis T. Rogers, Richard J. Kryscio, Anika M. S. Hartz, Björn Bauer

Sanders-Brown Center on Aging Faculty Publications

Abstract
Glioblastoma (GBM) is one of the deadliest cancers. Treatment options are limited, and median patient survival is only several months. Translation of new therapies is hindered by a lack of GBM models that fully recapitulate disease heterogeneity. Here, we characterize two human GBM models (U87-luc2, U251-RedFLuc). In vitro, both cell lines express similar levels of luciferase and show comparable sensitivity to temozolomide and lapatinib exposure. In vivo, however, the two GBM models recapitulate diferent aspects of the disease. U87-luc2 cells quickly grow into large, well-demarcated tumors; U251-RedFLuc cells form small, highly invasive tumors. Using a new method to assess …

An Il1rl1 Genetic Variant Lowers Soluble St2 Levels And The Risk Effects Of Apoe-Ε4 In Female Patients With Alzheimer’S Disease, Yuanbing Jiang, Xiaopu Zhou, Hui Yi Wong, Li Ouyang, Fanny C. F. Ip, Vicky M. N. Chau, Shun-Fat Lau, Wei Wu, Daniel Y. K. Wong, Heukjin Seo, Wing-Yu Fu, Nicole C. H. Lai, Yuewen Chen, Alzheimer’S Disease Neuroimaging Initiative, Charles D. Smith, Gregory A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Sanders-Brown Center on Aging Faculty Publications

Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR–Cas9 genome editing identified rs1921622, a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622, demonstrated that decreased sST2 levels lower AD …

Exogenous Short Chain Fatty Acid Effects In App/Ps1 Mice, Diana J. Zajac, Benjamin C. Shaw, David J. Braun, Stefan J. Green, Joshua M. Morganti, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

Elucidating the impact of the gut microbiome on Alzheimer’s Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and …

Sex Differences In The Genetic Architecture Of Cognitive Resilience To Alzheimer’S Disease, Jaclyn M. Eissman, Logan Dumitrescu, Emily R. Mahoney, Alexandra N. Smith, Shubhabrata Mukherjee, Michael L. Lee, Phoebe Scollard, Seo Eun Choi, William S. Bush, Corinne D. Engelman, Qiongshi Lu, David W. Fardo, Emily H. Trittschuh, Jesse Mez, Catherine C. Kaczorowski, Hector Hernandez Saucedo, Keith F. Widaman, Rachel F. Buckley, Michael J. Properzi, Elizabeth C. Mormino, Hyun Sik Yang, Theresa M. Harrison, Trey Hedden, Kwangsik Nho, Shea J. Andrews, Douglas Tommet, Niran Hadad, R. Elizabeth Sanders, Douglas M. Ruderfer, Katherine A. Gifford, Xiaoyuan Zhong, Neha S. Raghavan, Badri Vardarajan, Margaret A. Pericak-Vance, Lindsay A. Farrer, Li San Wang, Carlos Cruchaga, Gerard D. Schellenberg, Nancy J. Cox, Jonathan L. Haines, C. Dirk Keene, Andrew J. Saykin, Eric B. Larson, Reisa A. Sperling, Richard Mayeux, Michael L. Cuccaro, David A. Bennett, Julie A. Schneider, Paul K. Crane, Angela L. Jefferson, Timothy J. Hohman

Sanders-Brown Center on Aging Faculty Publications

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience.

We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts …

Enlarged Perivascular Spaces Are Negatively Associated With Montreal Cognitive Assessment Scores In Older Adults, Timothy J. Libecap, Valentinos Zachariou, Christopher E. Bauer, Donna M. Wilcock, Gregory A. Jicha, Flavius D. Raslau, Brian T. Gold

Sanders-Brown Center on Aging Faculty Publications

Emerging evidence suggests that enlarged perivascular spaces (ePVS) may be a clinically significant neuroimaging marker of global cognitive function related to cerebral small vessel disease (cSVD). We tested this possibility by assessing the relationship between ePVS and both a standardized measure of global cognitive function, the Montreal Cognitive Assessment (MoCA), and an established marker of cSVD, white matter hyperintensity volume (WMH) volume. One hundred and eleven community-dwelling older adults (56–86) underwent neuroimaging and MoCA testing. Quantification of region-specific ePVS burden was performed using a previously validated visual rating method and WMH volumes were computed using the standard ADNI pipeline. Separate …

Impact Of The Covid-19 Pandemic On Daily Life, Mood, And Behavior Of Adults With Down Syndrome, Sigan L. Hartley, Victoria Fleming, Brianna Piro-Gambetti, Annie Cohen, Beau M. Ances, Michael A. Yassa, Adam M. Brickman, Benjamin L. Handen, Elizabeth Head, Mark Mapstone, Bradley T. Christian, Ira T. Lott, Eric Doran, Shahid Zaman, Sharon Krinsky-Mchale, Frederick A. Schmitt, Christy L. Hom, Nicole Schupf

Sanders-Brown Center on Aging Faculty Publications

Background: The Down syndrome population has been disproportionately affected by Coronavirus 2019 (COVID-19) in terms of experiencing severe illness and death. Societal efforts to curb the spread of COVID-19 may also have taken a heavy toll on the daily lives of individuals with Down syndrome.

Objective/hypothesis: The goal of the study was to understand how the COVID-19 pandemic has altered daily life (including residence, employment, and participation in adult disability day programs) and influenced the mood and behavior of adults with Down syndrome.

Methods: Between September 2020 and February 2021, caregivers of 171 adults with Down syndrome (aged …

Plasmalogen Deficiency: A Risk Factor For Dementias And Potential Treatment Target, Mitchel A. Kling, Mallika Mendu, Rima F. Kaddurah-Daouk, Sheldon Jordan, Dayan B. Goodenowe

Rowan-Virtua Research Day

Altered lipid metabolism is implicated in the risk of sporadic Alzheimer’s disease (AD) and related dementias (ADRD); however, the precise mechanisms accounting for findings from observational studies remains to be fully elucidated.

Plasmalogens are a subclass of integral membrane phospholipids with unique properties that appear to play important roles relevant to the pathophysiology of AD and ADRD, including vesicle fusion necessary for synaptic neurotransmitter release, modulation of membrane fluidity and microdomain dynamics, membrane antioxidant functions, and neuroprotection. Like the more familiar phosphatides, plasmalogens are synthesized on a 3-carbon glycerol backbone; however, they differ from phosphatides by the presence of a …

Extracellular Vesicles Released After Cranial Radiation: An Insight Into An Early Mechanism Of Brain Injury, Suriyan Sukati, Jenni Ho, Luksana Chaiswing, Pradoldej Sompol, Harshul Shreekant Pandit, Wendy Wei, Tadahide Izumi, Quan Chen, Heidi Weiss, Teresa Noel, Subbarao Bondada, D. Allan Butterfield, Daret K. St. Clair

Sanders-Brown Center on Aging Faculty Publications

Cranial radiation is important for treating both primary brain tumors and brain metastases. A potential delayed side effect of cranial radiation is neurocognitive function decline. Early detection of CNS injury might prevent further neuronal damage. Extracellular vesicles (EVs) have emerged as a potential diagnostic tool because of their unique membranous characteristics and cargos. We investigated whether EVs can be an early indicator of CNS injury by giving C57BJ/6 mice 10 Gy cranial IR. EVs were isolated from sera to quantify: 1) number of EVs using nanoparticle tracking analysis (NTA); 2) Glial fibrillary acidic protein (GFAP), an astrocyte marker; and 3) …

Association Between Concussions And Suicidality In High School Students In The United States, Grant L. Iverson, Justin E. Karr

Sanders-Brown Center on Aging Faculty Publications

Importance: Prior research has shown a statistically significant association between sustaining a concussion and suicidality in adolescents, but this prior research controlled for relatively few variables predictive of suicidality.

Objective: To examine whether sustaining a concussion remained a significant predictor of suicidality after controlling for relevant covariates (e.g., sexual abuse/assault, bullying, substance use, depression), hypothesizing that the relationship between concussion and suicidality would become non-significant after controlling for these variables.

Design: This study involved secondary data analysis of the 2019 Youth Risk Behavior Surveillance (YRBS) System, a national cross-sectional study of adolescents. Analyses were stratified by gender. …

Manifestations Of Alzheimer’S Disease Genetic Risk In The Blood Are Evident In A Multiomic Analysis In Healthy Adults Aged 18 To 90, Laura Heath, John C. Earls, Andrew T. Magis, Sergey A. Kornilov, Jennifer C. Lovejoy, Cory C. Funk, Noa Rappaport, Benjamin A. Logsdon, Lara M. Mangravite, Brian W. Kunkle, Eden R. Martin, Adam C. Naj, Nilüfer Ertekin-Taner, Todd E. Golde, Leroy Hood, Nathan D. Price, Erin Abner, David W. Fardo, Linda J. Van Eldik, Alzheimer’S Disease Genetics Consortium

Sanders-Brown Center on Aging Faculty Publications

Genetics play an important role in late-onset Alzheimer’s Disease (AD) etiology and dozens of genetic variants have been implicated in AD risk through large-scale GWAS meta-analyses. However, the precise mechanistic effects of most of these variants have yet to be determined. Deeply phenotyped cohort data can reveal physiological changes associated with genetic risk for AD across an age spectrum that may provide clues to the biology of the disease. We utilized over 2000 high-quality quantitative measurements obtained from blood of 2831 cognitively normal adult clients of a consumer-based scientific wellness company, each with CLIA-certified whole-genome sequencing data. Measurements included: clinical …