Neurology Commons^™

National Trends Of Vascular Risk Factor Control Among Stroke Survivors: From The National Health And Nutrition Examination Survey 2009 To 2020, Hend Mansoor, Daniel Manion, Kara Jo Swafford, Gregory A. Jicha, Daniela Claudia Moga

Neurology Faculty Publications

BACKGROUND: Contemporary data describing the national trends on vascular risk factor control among stroke survivors are limited.

METHODS AND RESULTS: This is a cross-sectional analysis of the National Health and Nutrition Examination Survey cycles 2009 to 2010 to 2017 to March 2020. Adults (≥18 years of age) with a self-reported diagnosis of stroke were identified. Age- adjusted trends in hypertension, diabetes, and hyperlipidemia control were examined. Sex and racial differences in vascular risk factor control were also investigated. Among 32 497 adult individuals who participated in the National Health and Nutrition Examination Survey, 1354 participants (4.2%) self-reported a prior diagnosis …

Higher Glycemic Index And Glycemic Load Diet Is Associated With Slower Disease Progression In Amyotrophic Lateral Sclerosis, Ikjae Lee, Hiroshi Mitsumoto, Seonjoo Lee, Edward J. Kasarskis, Michael Rosenbaum, Pam Factor-Litvak, Jeri W. Nieves

Neurology Faculty Publications

Objective: High-caloric diets may slow the progression of amyotrophic lateral sclerosis; however, key macronutrients have not been identified. We examined whether dietary macronutrients are associated with the rate of progression and length of survival among the prospective cohort study participants.

Methods: Participants with a confirmed diagnosis of sporadic amyotrophic lateral sclerosis enrolled in the Multicenter Cohort Study of Oxidative Stress were included (n = 304). We evaluated baseline macronutrient intake assessed by food frequency questionnaire in relation to change in revised amyotrophic lateral sclerosis functional rating scale total- score, and tracheostomy-free survival using linear regression and Cox proportional hazard models. …

Alzheimer’S Disease And Inflammatory Biomarkers Positively Correlate In Plasma In The Uk-Adrc Cohort, Kate E. Foley, Zachary Winder, Tiffany L. Sudduth, Barbara J. Martin, Peter T. Nelson, Gregory Jicha, Jordan P. Harp, Erica M. Weekman, Donna M. Wilcock

Neurology Faculty Publications

INTRODUCTION: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia. METHODS: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer’s Disease Research Center cohort. We evaluated six Alzheimer’s disease (AD)- and neurodegeneration-related (Aβ40, Aβ42, Aβ42/40, p- tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform. Statistics were performed to assess correlations. RESULTS: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD–inflammatory biomarker correlations showed significant associations between AD and inflammatory …

Pathologic Correlates Of Aging-Related Tau Astrogliopathy: Artag Is Associated With Late-Nc And Cerebrovascular Pathologies, But Not With Adnc, Yuriko Katsumata, Xian Wu, Khine Zin Aung, Kathryn Gauthreaux, Charles Mock, Shelley L. Forrest, Gabor G. Kovacs, Peter T. Nelson

Neurology Faculty Publications

Age-related tau astrogliopathy (ARTAG) is detectable in the brains of over one-third of autopsied persons beyond age 80, but the pathoetiology of ARTAG is poorly understood. Insights can be gained by analyzing risk factors and comorbid pathologies. Here we addressed the question of which prevalent co-pathologies are observed with increased frequency in brains with ARTAG. The study sample was the National Alzheimer’s Coordinating Center (NACC) data set, derived from multiple Alzheimer’s disease research centers (ADRCs) in the United States. Data from persons with unusual conditions (e.g. frontotemporal dementia) were excluded leaving 504 individual autopsied research participants, clustering from 20 different …

Azithromycin Reduces Hemoglobin-Induced Innate Neuroimmune Activation, Chirayu D. Pandya, Hemendra J. Vekaria, Miriam Zamorano, Amanda L. Trout, Rodney M. Ritzel, Gary Guzman, Christopher Bolden, Patrick G. Sullivan

Neurology Faculty Publications

Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH and surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, surgery is not a cure for intrinsic brain injury from IVH, and is performed in a subacute time frame. Like many neurological diseases and injuries, innate immune activation is implicated in the pathogenesis of IVH. Innate immune activation is a pharmaceutically targetable mechanism to reduce brain injury and post-hemorrhagic hydrocephalus after IVH. Here, we tested the macrolide antibiotic azithromycin, which has immunomodulatory properties, to …

Amperometric Bio-Sensing Of Lactate And Oxygen Concurrently With Local Field Potentials During Status Epilepticus, Eliana Fernandes, Ana Ledo, Greg A. Gerhardt, Rui M. Barbosa

Neurology Faculty Publications

Epilepsy is a prevalent neurological disorder with a complex pathogenesis and unpredictable nature, presenting limited treatment options in >30 % of affected individuals. Neurometabolic abnormalities have been observed in epilepsy patients, suggesting a disruption in the coupling between neural activity and energy metabolism in the brain. In this study, we employed amperometric biosensors based on a modified carbon fiber microelectrode platform to directly and continuously measure lactate and oxygen dynamics in the brain extracellular space. These biosensors demonstrated high sensitivity, selectivity, and rapid response time, enabling in vivo measurements with high temporal and spatial resolution. In vivo recordings in the …

Hiv-1 Mrna Knockdown With Crispr/Cas9 Enhances Neurocognitive Function, Kristen A. Mclaurin, Hailong Li, Kamel Khalili, Charles F. Mactutus, Rosemarie M. Booze

Neurology Faculty Publications

Mixed glia are infiltrated with HIV-1 virus early in the course of infection leading to the development of a persistent viral reservoir in the central nervous system. Modification of the HIV-1 genome using gene editing techniques, including CRISPR/Cas9, has shown great promise towards eliminating HIV-1 viral reservoirs; whether these techniques are capable of removing HIV-1 viral proteins from mixed glia, however, has not been systematically evaluated. Herein, the efficacy of adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing for eliminating HIV-1 messenger RNA (mRNA) from cortical mixed glia was evaluated in vitro and in vivo. In vitro, a within-subjects experimental design was …

Cancer Research Provides A Model For Advancing Clinical Trials In Dementia In The Era Of Disease-Modifying Alzheimer’S-Type Dementia Therapies, Gregory Jicha, Thomas Tucker, Susanne Arnold, Peter T. Nelson

Neurology Faculty Publications

Dementia and cancer are multifactorial, widely-feared, age-associated clinical syndromes that are increasing in prevalence. There have been major breakthroughs in clinical cancer research leading to some effective treatments, whereas the field of dementia has achieved comparatively limited success in clinical research. The lessons of cancer research may help those in the dementia research field in confronting some of the dilemmas faced when the clinical care regimen is not entirely safe or efficacious. Cancer clinical trials have assumed that untreated individuals with cancer are at high risk for morbidity and mortality after primary diagnoses. Thus, patients deserve a choice of clinical …

Estimating Socio-Economic Status For Alzheimer’S Disease Trials, D. M. Rentz, J. D. Grill, D. P. Molina-Henry, Gregory Jicha, Michael S. Rafii, A. Liu, Reisa A. Sperling, Paul Aisen, R. Raman

Neurology Faculty Publications

INTRODUCTION: Metrics of a participant’s socioeconomic status (SES) are not routinely collected or standardized in clinical trials. This omission limits the ability to evaluate the generalizability of trial results and restricts clinicians from confidently interpreting the efficacy of new treatments across important sub-populations. METHODS: We adapted an SES measure of social disparity; the Hollingshead Two Factor Index of Social Position, which combines education and occupation into a single metric. We modernized the 1965 occupations to reflect the 2017 careers tabulated by the US Bureau of Labor Statistics. We currently use this adapted measure in Alzheimer’s Clinical Trials Consortium studies. RESULTS: …

Clinical Trial Protocol For Beach: A Phase 2a Study Of Mw189 In Patients With Acute Nontraumatic Intracerebral Hemorrhage, Radhika Avadhani, Wendy C. Ziai, Richard E. Thompson, W. Andrew Mould, Karen Lane, Angeline Nanni, Michael Lacobelli, Matthew F. Sharrock, Lauren H. Sansing, Linda J. Van Eldik, Daniel F. Hanley

Neurology Faculty Publications

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability …

Multiomics Analysis To Explore Blood Metabolite Biomarkers In An Alzheimer’S Disease Neuroimaging Initiative Cohort, Takaki Oka, Yuki Matsuzawa, Momoka Tsuneyoshi, Yoshitaka Nakamura, Ken Aoshima, Hiroshi Tsugawa, Alzheimer’S Disease Metabolomics Consortium

Neurology Faculty Publications

Alzheimer’s disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD …

A Brief Report On Juvenile Amyotrophic Lateral Sclerosis Cases In The United States National Als Registry: 2010– 2018, Jaime Raymond, Jasmine Berry, Edward J. Kasarskis, Theodore Larson, D. Kevin Horton, Paul Mehta

Neurology Faculty Publications

Juvenile ALS (jALS) is a rare form of ALS, defined as symptom onset before age 25. This report describes the demographic characteristics of confirmed and likely jALS cases in a large cohort of ALS patients ascertained in the National ALS Registry (Registry) from 2010 to 2018. Patients in the Registry must be at least 18 years of age. Of the 44 identified patients, 37.8% were diagnosed at age 24, were more likely to be nonwhite (54.5%), male (79.5%), and live in the Midwest or Northeast regions (54.5%) of the US. Some 68.9% of the jALS cases were received from federal …

The Differential Proteomic Response To Ischemic Stroke In Appalachian Subjects Treated With Mechanical Thrombectomy, Christopher J. Mclouth, Benton Maglinger, Jacqueline A. Frank, Kristin J. Hazelwood, Jordan P. Harp, Will Cranford, Shivani Pahwa, David Dornbos Iii, Amanda L. Trout, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Neurology Faculty Publications

Introduction The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. Methods There were 81 subjects that met inclusion criteria for this …

Rare Variant Analyses Validate Known Als Genes In A Multi-Ethnic Population And Identifies Antxr2 As A Candidate In Pls, Tess D. Pottinger, Joshua E. Motelow, Gundula Povysil, Cristiane A. Martins Moreno, Zhong Ren, Hemali Phatnani, The New York Genome Center Als Sequencing Consortium, Timothy J. Aitman, Javier Santoyo‑Lopez, Scottish Genomes Partnership, Hiroshi Mitsumoto, Als Cosmos Study Group, Pls Cosmos Study Group, Gtac Investigators, David B. Goldstein, Matthew B. Harms

Neurology Faculty Publications

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people world‑ wide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible …

Astrocytic Mitochondrial Transfer To Brain Endothelial Cells And Pericytes In Vivo Increases With Aging, Gopal V. Velmurugan, Hemendra J. Vekaria, Samir P. Patel, Patrick G. Sullivan, W. Brad Hubbard

Neurology Faculty Publications

Intercellular mitochondrial transfer (IMT) is an intriguing biological phenomenon where mitochondria are transferred between different cells and notably, cell types. IMT is physiological, occurring in normal conditions, but also is utilized to deliver healthy mitochondria to cells in distress. Transferred mitochondria can be integrated to improve cellular metabolism, and mitochondrial function. Research on the mitochondrial transfer axis between astrocytes and brain capillaries in vivo is limited by the cellular heterogeneity of the neurovascular unit. To this end, we developed an inducible mouse model that expresses mitochondrial Dendra2 only in astrocytes and then isolated brain capillaries to remove all intact astrocytes. …

Detecting Cognitive Decline In High-Functioning Older Adults: The Relationship Between Subjective Cognitive Concerns, Frequency Of High Neuropsychological Test Scores, And The Frontoparietal Control Network, Justin E. Karr, Jonathan G. Hakun, Daniel B. Elbich, Cristina N. Pinheiro, Frederick A. Schmitt

Neurology Faculty Publications

Objective: Neuropsychologists have difficulty detecting cognitive decline in high-functioning older adults because greater neurological change must occur before cognitive performances are low enough to indicate decline or impairment. For high-functioning older adults, early neurological changes may correspond with subjective cognitive concerns and an absence of high scores. This study compared high- functioning older adults with and without subjective cognitive concerns, hypothesizing those with cognitive concerns would have fewer high scores on neuropsychological testing and lower frontoparietal network volume, thickness, and connectivity.

Method: Participants had high estimated premorbid functioning (e.g., estimated intelligence ≥75th percentile or college-educated) and were divided based on …

Impact Of Amyloid And Cardiometabolic Risk Factors On Prognostic Capacity Of Plasma Neurofilament Light Chain For Neurodegeneration, Keun You Kim, Eosu Kim, Jun-Young Lee, Alzheimer’S Disease Neuroimaging Initiative

Neurology Faculty Publications

Background Plasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer’s disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid‑β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obesity. This longitudinal observational study using the Alzheimer’s Disease Neuroimaging Initiative cohort investigated how these conditions influence the prognostic capacity of plasma NfL. Methods Non‑demented participants (cognitively unimpaired or mild cognitive impairment) underwent repeated assessments including the Alzheimer’s Disease Assessment Scale‑Cognitive subscale (ADAS‑Cog) scores, hippocampal volumes, and white matter hyperintensity (WMH) volumes at 6‑ or 12‑month …

Astrocytic Stress Response Is Induced By Exposure To Astrocyte-Binding Antibodies Expressed By Plasmablasts From Pediatric Patients With Acute Transverse Myelitis, Chad Smith, Kiel M. Telesford, Sara G. M. Piccirillo, Yamhilette Licon‑Munoz, Wei Zhang, Key M. Tse, Jacqueline R. Rivas, Chaitanya Joshi, Dilan S. Shah, Angela X. Wu, Ritu Trivedi, Scott Christley, Yu Qian, Lindsay G. Cowell, Richard H. Scheuermann, Ann M. Stowe, Linda Nguyen, Benjamin M. Greenberg, Nancy L. Monson

Neurology Faculty Publications

Background Pediatric acute transverse myelitis (ATM) accounts for 20–30% of children presenting with a first acquired demyelinating syndrome (ADS) and may be the first clinical presentation of a relapsing ADS such as multiple sclerosis (MS). B cells have been strongly implicated in the pathogenesis of adult MS. However, little is known about B cells in pediatric MS, and even less so in pediatric ATM. Our lab previously showed that plasmablasts (PB), the earliest B cell subtype producing antibody, are expanded in adult ATM, and that these PBs produce self‑reactive antibodies that target neurons. The goal of this study was to …

Using Digital Pathology To Analyze The Murine Cerebrovasculature, Dana M. Niedowicz, Jenna L. Gollihue, Erica M. Weekman, Panhavuth Phe, Donna M. Wilcock, Christopher M. Norris, Peter T. Nelson

Neurology Faculty Publications

Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research. However, mouse brain tissue presents a formidable set of technical challenges, including potentially high background staining and crossreactivity of endogenous IgG. Formalin-fixed paraffin-embedded (FFPE) and fixed frozen sections, both of which are widely used, may require different methods. In this study, we optimized blood vessel staining in mouse brain tissue, testing both FFPE and frozen fixed …

Anterior Circulation Location-Specific Results For Stent- Assisted Coiling – Carotid Versus Distal Aneurysms: 1- Year Outcomes From The Neuroform Atlas Stent Pivotal Trial, Ricardo A. Hanel, Gustavo M. Cortez, Brian T. Jankowitz, Eric Sauvageau, Amin Aghaebrahim, Eugene Lin, Ashutosh P. Jadhav, Bradley Gross, Ahmad Khaldi, Rishi Gupta, Donald Frei, David Loy, Lori Lyn Price, Steven W. Hetts, Osama O. Zaidat, Atlas Investigators

Neurology Faculty Publications

Background The Neuroform Atlas Stent System is an established treatment modality for unruptured anterior and posterior circulation intracranial aneurysms. Location-specific results are needed to guide treatment decision- making. However, it is unclear whether there are differences in safety and efficacy outcomes between carotid and more distal anterior circulation aneurysms. Methods The ATLAS IDE trial was a prospective, multicenter, single- arm, open-label interventional study that evaluated the safety and efficacy of the Neuroform Atlas Stent System. We compared differences in efficacy and safety outcomes of proximal internal carotid artery (ICA) versus distal and bifurcation anterior circulation aneurysms.

Results Of 182 cases, …

Estrogen’S Sex-Specific Effects On Ischemic Cell Death And Estrogen Receptor Mrna Expression In Rat Cortical Organotypic Explants, Amanda L. Trout, Christopher J. Mclouth, Jenna Westberry, Tomoko Sengoku, Melinda E. Wilson

Neurology Faculty Publications

Estrogens, such as the biologically active 17-β estradiol (E2), regulate not only reproductive behaviors in adults, but also influence neurodevelopment and neuroprotection in both females and males. E2, contingent upon the timing and concentration of the therapy, is neuroprotective in female and male rodent models of stroke. In Vivo studies suggest that E2 may partially mediate this neuroprotection, particularly in the cortex, via ERα. In Vitro studies, utilizing a chemically induced ischemic injury in cortical explants from both sexes, suggest that ERα or ERβ signaling is needed to mediate the E2 protection. Since we know that the timing and concentration …

Different Cohort, Disparate Results: Selection Bias Is A Key Factor In Autopsy Cohorts, Kathryn Gauthreaux, Walter A. Kukull, Karin B. Nelson, Charles Mock, Yen-Chi Chen, Kwun C. G. Chan, David W. Fardo, Yuriko Katsumata, Erin L. Abner, Peter T. Nelson

Neurology Faculty Publications

INTRODUCTION: Research-oriented autopsy cohorts provide critical insights into dementia pathobiology. However, different studies sometimes report disparate findings, partially because each study has its own recruitment biases. We hypothesized that a straightforward metric, related to the percentage of research volunteers cognitively normal at recruitment, would predict other inter-cohort differences.

METHODS: The National Alzheimer’s Coordinating Center (NACC) provided data on N = 7178 autopsied participants from 28 individual research centers. Research cohorts were grouped based on the proportion of participants with normal cognition at initial clinical visit.

RESULTS: Cohorts with more participants who were cognitively normal at recruitment contained more individuals who …

Evaluation Of Blood-Based, Extracellular Vesicles As Biomarkers For Aging-Related Tdp-43 Pathology, Charisse N. Winston, Sonal Sukreet, Haley Lynch, Virginia M. -Y. Lee, Donna M. Wilcock, Peter T. Nelson, Robert A. Rissman

Neurology Faculty Publications

Introduction: Limbic predominant age related TDP-43 encephalopathy neuropathological change (LATE-NC) is a recently characterized brain disease that mimics Alzheimer’s disease (AD) clinically. To date, LATE-NC is difficult to diagnose antemortem using clinical information or biomarkers. Recent studies suggest concentrations of extracellular vesicle (EVs) protein cargo derived from neuronal and glial cells may serve as useful diagnostic biomarkers for AD and other neurodegenerative diseases.

Methods: TDP-43 was evaluated in neuronal (NDEVs), astrocyte (ADEVs), and microglial derived extracellular vesicles (MDEVs). EV preparations were isolated from the plasma of research subjects with autopsy-confirmed diagnoses, including many with LATE (n = 22). …

Intensive Versus Standard Treatment Of Hyperglycemia In Acute Ischemic Stroke Patient: A Randomized Clinical Trial Subgroups Analysis, Michael T. Torbey, Qi Pauls, Nina Gentile, Mercedes Falciglia, William Meurer, Creed L. Pettigrew, Valerie L. Durkalski-Mauldin, Thomas Bleck, Askiel Bruno

Neurology Faculty Publications

Background: Benefit from blood glucose (BG) control during acute ischemic stroke may depend on glycemic parameters. We evaluated for associations between the SHINE (Stroke Hyperglycemia Insulin Network Effort) randomized treatment group and the SHINE predefined 90-day functional outcome, within-patient subgroups defined by various glycemic parameters.

Methods: The SHINE Trial randomized 1151 patients within 12 hours with acute ischemic stroke and hyperglycemia to standard (target BG 80-179 mg/dL) or intensive (target BG 80-130 mg/dL) BG control for 72 hours. We predefined 6 glycemic parameters: acute BG level, absence versus presence of diagnosed and undiagnosed diabetes, hemoglobin A1c, glycemic gap …

Typical Sounding Atypical Diagnostic Conundrum -- A Rare Case Of Mycobacterium Avium Complex (Mac) Presenting With Multiple Cranial Nerve Involvement, Ashwini Kini, Karl Echiverri, Edward J. Escott, Padmaja Sudhakar

Neurology Faculty Publications

Background

MAC infections rarely cause symptomatic systemic infection in immunocompetent healthy individuals. This case brings to light a rare such presentation that gives us a learning point about keeping a strong pre-clinical suspicion for this condition in patients whom lung imaging reveals suspicious cavitary lesions. Starting empiric therapy while awaiting culture results may be considered after weighing risks and benefits in order to achieve the morbidity and mortality associated with the disease.

Case report

A 54 year-old white male presented for evaluation of progressively worsening vertigo, imbalance, vertical diplopia, facial diplegia, bilateral hyperacusis followed by hearing loss, dysphagia, and dysarthria …

Dementia Risk Reduction: Why Haven't The Pharmacological Risk Reduction Trials Worked? An In-Depth Exploration Of Seven Established Risk Factors, Ruth Peters, John Breitner, Sarah James, Gregory A. Jicha, Pierre-Francois Meyer, Marcus Richards, A. David Smith, Hussein N. Yassine, Erin L. Abner, Atticus H. Hainsworth, Patrick G. Kehoe, Nigel Beckett, Christopher Weber, Craig Anderson, Kaarin J. Anstey, Hiroko H. Dodge

Neurology Faculty Publications

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need …

Multifocal Myoclonus As A Presentation Of Levetiracetam Toxicity., Mei Bou Nasif, Shweta Varade, Mohamad Z. Koubeissi

Neurology Faculty Publications

No abstract provided.

Hypothalamic Hamartomas: Evolving Understanding And Management., Nathan T. Cohen, J Helen Cross, Alexis Arzimanoglou, Samuel F Berkovic, John F Kerrigan, Ilene Penn Miller, Erica Webster, Lisa Soeby, Arthur Cukiert, Dale K Hesdorffer, Barbara L Kroner, Clifford B Saper, Andreas Schulze-Bonhage, William D. Gaillard

Neurology Faculty Publications

No abstract provided.

Cognitive And Behavioral Domains That Reliably Differentiate Normal Aging And Dementia In Down Syndrome, Jordan P. Harp, Lisa M. Koehl, Kathryn L. Van Pelt, Christy L. Hom, Eric Doran, Elizabeth Head, Ira T. Lott, Frederick A. Schmitt

Neurology Faculty Publications

Primary care integration of Down syndrome (DS)-specific dementia screening is strongly advised. The current study employed principal components analysis (PCA) and classification and regression tree (CART) analyses to identify an abbreviated battery for dementia classification. Scale- and subscale-level scores from 141 participants (no dementia n = 68; probable Alzheimer’s disease n = 73), for the Severe Impairment Battery (SIB), Dementia Scale for People with Learning Disabilities (DLD), and Vineland Adaptive Behavior Scales—Second Edition (Vineland-II) were analyzed. Two principle components (PC1, PC2) were identified with the odds of a probable dementia diagnosis increasing 2.54 times per PC1 unit increase and by …

Pulmonary Function Decline In Amyotrophic Lateral Sclerosis, Terry D. Heiman-Patterson, Ossama Khazaal, Daohai Yu, Michael E. Sherman, Edward J. Kasarskis, Carlayne E. Jackson, Peg Niv Study Group

Neurology Faculty Publications

Background: There has been no comprehensive longitudinal study of pulmonary functions (PFTS) in ALS determining which measure is most sensitive to declines in respiratory muscle strength. Objective: To determine the longitudinal decline of PFTS in ALS and which measure supports Medicare criteria for NIV initiation first. Methods: Serial PFTs (maximum voluntary ventilation (MVV), maximum inspiratory pressure measured by mouth (MIP) or nasal sniff pressure (SNIP), maximum expiratory pressure (MEP), and Forced Vital Capacity (FVC)) were performed over 12 months on 73 ALS subjects to determine which measure showed the sentinel decline in pulmonary function. The rate of decline for each …