Neurology Commons^™

Multimorbidity And Cognition Among Canadian Older Adults: A Three-Decade Perspective, Juan Camilo Vargas Gonzalez

Electronic Thesis and Dissertation Repository

Background: Scarce information exists about whether the relationship between multimorbidity and cognitive decline has changed over the past decades.

Objectives: 1) To summarize knowledge about the association of multimorbidity and cognitive decline by performing a systematic review. 2) To estimate the association between multimorbidity in two cohorts selected three decades apart. 3)To identify which multimorbidity combinations have the strongest associations with cognitive decline 4) To identify protective factors that reduce the risk of cognitive decline in the presence of multimorbidity.

Methods: We performed a systematic review following the PRISMA statement. We then addressed objectives 2-4 by analyzing data from two …

Immunohistochemical Detection And Prognostic Significance Of P53, Epidermal Growth Factor Receptor, Murine Double Minute 2, And Isocitrate Dehydrogenase 1 In Glioblastoma Multiforme Patients Of Pakistan, Syed Muhammad Adnan Ali, Muhammad Shahzad Shamim, Syed Ather Enam, Zubair Ahmad, Yumna Adnan, Hasnain Ahmed Farooqui

Department of Surgery

Introduction: Glioblastoma multiforme (GBM) is one of the deadliest cranial tumors occurring in adults. Various biomarkers have been tested for their significance in diagnosis, prognosis, and treatment of GBM. Some well-studied markers in GBM are Isocitrate dehydrogenase 1 (IDH1), Murine double minute 2 (MDM2), Epidermal Growth Factor Receptor (EGFR), and p53. The aim of this study was to investigate the protein expression of these markers in GBM patients of Pakistan.
Methods: A total of 102 surgically resected formalin-fixed paraffin-embedded specimens from patients diagnosed and treated at Aga Khan University Hospital were included in this study. Immunohistochemistry (IHC) for IDH1, MDM2, …

Covid-19 In Cns And Pns: Basic And Clinical Focus On The Mechanisms Of Infection And New Tools For The Therapeutic Approach, Jorge Matias-Guiu, Jordi A. Matias-Guiu, Carmen Garrido, Genaro Pimienta, Patricio F. Reyes, Abdul Mannan Baig, Ulises Gomez-Pinedo

Department of Biological & Biomedical Sciences

No abstract provided.

Genetic Contributors Of Incident Stroke In 10,700 African Americans With Hypertension: A Meta-Analysis From The Genetics Of Hypertension Associated Treatments And Reasons For Geographic And Racial Differences In Stroke Studies, Nicole D. Armstrong, Vinodh Srinivasasainagendra, Amit Patki, Rikki M. Tanner, Bertha A. Hidalgo, Hemant K. Tiwari, Nita A. Limdi, Ethan M. Lange, Leslie A. Lange, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals.

Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs …

Analysis Of Genes (Tmem106b, Grn, Abcc9, Kcnmb2, And Apoe) Implicated In Risk For Late-Nc And Hippocampal Sclerosis Provides Pathogenetic Insights: A Retrospective Genetic Association Study, Adam J. Dugan, Peter T. Nelson, Yuriko Katsumata, Lincoln M. P. Shade, Kevin L. Boehme, Merilee A. Teylan, Matthew D. Cykowski, Shubhabrata Mukherjee, John S. K. Kauwe, Timothy J. Hohman, Julie A. Schneider, Alzheimer’S Disease Genetics Consortium, David W. Fardo

Biostatistics Faculty Publications

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a role. Previous studies found associations between LATE-NC phenotypes and specific genes: TMEM106B, GRN, ABCC9, KCNMB2, and APOE. Data from research participants with genomic and autopsy measures from the National Alzheimer’s Coordinating Center (NACC; n = 631 subjects included) and the Religious Orders Study and Memory …

Association Between Air Pollution And Incidence Of Dementia: A Systematic Review And Meta-Analysis Of Cohort Studies, Ehsan Abolhasani

Electronic Thesis and Dissertation Repository

Objective. To estimate the risk of dementia in association with exposure to air pollutants.

Methods. Six databases were searched. Cohort studies that reported the hazard ratio (HR) of dementia in association with exposure to air pollutants in adults > 40y were included. For all meta-analyses, the random-effects model was used.

Results. A total of 16 and 13 studies were included in the systematic review and the meta-analysis, respectively. Risk of dementia increased by 4% per 1μg/m³ increase in fine particulate matter level (HR, 1.04; 95%CI, [1.02, 1.06]), which was statistically significant. The risk of dementia increased by 3% per 10μg/m …

The Association Of Circulating Amylin With Β-Amyloid In Familial Alzheimer's Disease, Han Gia Ly, Nirmal Verma, Savita Sharma, Deepak Kotiya, Sanda Despa, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Donna M. Wilcock, Larry B. Goldstein, Rita Guerreiro, José Brás, Angela J. Hanson, Suzanne Craft, Andrew J. Murray, Geert Jan Biessels, Claire Troakes, Henrik Zetterberg, John Hardy, Tammaryn Lashley, Alzheimer’S Disease Exome Sequencing Group, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Introduction

This study assessed the hypothesis that circulating human amylin (amyloid‐forming) cross‐seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).

Methods

Evidence of amylin‐AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non‐APP/PS1 rats.

Results

Amylin‐Aβ cross‐seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected …

Memory-Related Frontal Brainwaves Predict Transition To Mild Cognitive Impairment In Healthy Older Individuals Five Years Before Diagnosis, Yang Jiang, Juan Li, Frederick A. Schmitt, Gregory A. Jicha, Nancy B. Munro, Xiaopeng Zhao, Charles D. Smith, Richard J. Kryscio, Erin L. Abner

Behavioral Science Faculty Publications

BACKGROUND: Early prognosis of high-risk older adults for amnestic mild cognitive impairment (aMCI), using noninvasive and sensitive neuromarkers, is key for early prevention of Alzheimer's disease. We have developed individualized measures in electrophysiological brain signals during working memory that distinguish patients with aMCI from age-matched cognitively intact older individuals.

OBJECTIVE: Here we test longitudinally the prognosis of the baseline neuromarkers for aMCI risk. We hypothesized that the older individuals diagnosed with incident aMCI already have aMCI-like brain signatures years before diagnosis.

METHODS: Electroencephalogram (EEG) and memory performance were recorded during a working memory task at baseline. The individualized baseline neuromarkers, …

Distinct Clinicopathologic Clusters Of Persons With Tdp-43 Proteinopathy, Yuriko Katsumata, Erin L. Abner, Shama Karanth, Merilee A. Teylan, Charles N. Mock, Matthew D. Cykowski, Edward B. Lee, Kevin L. Boehme, Shubhabrata Mukherjee, John S. K. Kauwe, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Peter T. Nelson

Biostatistics Faculty Publications

To better understand clinical and neuropathological features of TDP-43 proteinopathies, data were analyzed from autopsied research volunteers who were followed in the National Alzheimer’s Coordinating Center (NACC) data set. All subjects (n = 495) had autopsy-proven TDP-43 proteinopathy as an inclusion criterion. Subjects underwent comprehensive longitudinal clinical evaluations yearly for 6.9 years before death on average. We tested whether an unsupervised clustering algorithm could detect coherent groups of TDP-43 immunopositive cases based on age at death and extensive neuropathologic data. Although many of the brains had mixed pathologies, four discernible clusters were identified. Key differentiating features were age at …

Limbic-Predominant Age-Related Tdp-43 Encephalopathy Differs From Frontotemporal Lobar Degeneration, John L. Robinson, Sílvia Porta, Filip G. Garrett, Panpan Zhang, Sharon X. Xie, Eunran Suh, Vivianna M. Van Deerlin, Erin L. Abner, Gregory A. Jicha, Justin M. Barber, Virginia M-Y Lee, Edward B. Lee, John Q. Trojanowski, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

TAR-DNA binding protein-43 (TDP-43) proteinopathy is seen in multiple brain diseases. A standardized terminology was recommended recently for common age-related TDP-43 proteinopathy: limbic-predominant, age-related TDP-43 encephalopathy (LATE) and the underlying neuropathological changes, LATE-NC. LATE-NC may be co-morbid with Alzheimer’s disease neuropathological changes (ADNC). However, there currently are ill-defined diagnostic classification issues among LATE-NC, ADNC, and frontotemporal lobar degeneration with TDP-43 (FTLD-TDP). A practical challenge is that different autopsy cohorts are composed of disparate groups of research volunteers: hospital- and clinic-based cohorts are enriched for FTLD-TDP cases, whereas community-based cohorts have more LATE-NC cases. Neuropathological methods also differ across laboratories. Here, …

Structural Magnetic Resonance Imaging As A Diagnostic Biomarker Of Hiv-Associated Neurocognitive Disorders (Hand), Mikki Schantell

Capstone Experience

Objective: The goal of this study was to do an exploratory analysis to determine if gray matter brain volumes and cortical thickness measures obtained from structural magnetic resonance imaging (sMRI) can discriminate people with HIV-associated neurocognitive disorders (HAND), neurocognitively unimpaired people with HIV (NU PWH), and HIV-negative controls (HIV- controls) using linear discriminant analyses.

Methods: A total of 231 participants, including 110 PWH and 121 HIV- controls, completed a neuropsychological (NP) battery and an sMRI protocol. The bilateral gray matter volumes and cortical thickness brain regions were analyzed using 18 linear discriminant models to assess the discriminability of gray matter …

Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen

Neurology Faculty Publications

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …

Epilepsy Risk Among Survivors Of Intensive Care Unit Hospitalization For Sepsis, Tresah C. Antaya, Britney N. Allen, Lucie Richard, Salimah Z. Shariff, Gustavo Saposnik, Jorge Burneo

Neuroepidemiology Research Unit Project Summaries

Research Summary: Key Findings

• 407 (0.28%) patients developed epilepsy within 2 years of their ICU discharge, 103 (25.3%) of whom were exposed to sepsis.
• Sepsis survivors were significantly more likely to develop epilepsy, relative to non-septic ICU survivors.
• Among sepsis survivors, epilepsy risk increased with age and was higher among those with chronic kidney disease.

Intervention For Cognitive Reserve Enhancement In Delaying The Onset Of Alzheimer's Symptomatic Expression (Increase), A Randomized Controlled Trial: Rationale, Study Design, And Protocol, Daniela C. Moga, Brooke F. Beech, Erin L. Abner, Frederick A. Schmitt, Riham H. El Khouli, Ashley I. Martinez, Lynne Eckmann, Mark Huffmyer, Rosmy George, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

BACKGROUND: The course of Alzheimer's disease (AD) includes a 10-20-year preclinical period with progressive accumulation of amyloid β (Aβ) plaques and neurofibrillary tangles in the absence of symptomatic cognitive or functional decline. The duration of this preclinical stage in part depends on the rate of pathologic progression, which is offset by compensatory mechanisms, referred to as cognitive reserve (CR). Comorbid medical conditions, psychosocial stressors, and inappropriate medication use may lower CR, hastening the onset of symptomatic AD. Here, we describe a randomized controlled trial (RCT) designed to test the efficacy of a medication therapy management (MTM) intervention to reduce inappropriate …

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …

Tobacco Smoking And Dementia In A Kentucky Cohort: A Competing Risk Analysis, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Gregory E. Cooper, David W. Fardo, Frederick A. Schmitt, Richard J. Kryscio

Epidemiology and Environmental Health Faculty Publications

Tobacco smoking was examined as a risk for dementia and neuropathological burden in 531 initially cognitively normal older adults followed longitudinally at the University of Kentucky’s Alzheimer’s Disease Center. The cohort was followed for an average of 11.5 years; 111 (20.9%) participants were diagnosed with dementia, while 242 (45.6%) died without dementia. At baseline, 49 (9.2%) participants reported current smoking (median pack-years = 47.3) and 231 (43.5%) former smoking (median pack-years = 24.5). The hazard ratio (HR) for dementia for former smokers versus never smokers based on the Cox model was 1.64 (95% CI: 1.09, 2.46), while the HR for …

Evaluating Trajectories Of Episodic Memory In Normal Cognition And Mild Cognitive Impairment: Results From Adni, Xiuhua Ding, Richard J. Charnigo, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Alzheimer’S Disease Neuroimaging Initiative

Statistics Faculty Publications

BACKGROUND: Memory assessment is a key factor for the diagnosis of cognitive impairment. However, memory performance over time may be quite heterogeneous within diagnostic groups.

METHOD: To identify latent trajectories in memory performance and their associated risk factors, we analyzed data from Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were classified either as cognitively normal or as Mild Cognitive Impairment (MCI) at baseline and were administered the Rey Auditory Verbal Learning test (RAVLT) for up to 9 years. Group-based trajectory modeling on the 30-minute RAVLT delayed recall score was applied separately to the two baseline diagnostic groups.

RESULTS: There were …

The Risk Of New-Onset Epilepsy And Refractory Epilepsy In Older Adult Stroke Survivors, Jorge G. Burneo, Tresah C. Antaya, Britney N. Allen, Andrea Belisle, Salimah Z. Shariff, Gustavo Saposnik

Neuroepidemiology Research Unit Project Summaries

Research Summary: Key Findings

• Stroke is a common cause of epilepsy in older adults, but little is known about stroke-related epilepsy or its outcomes in this population.
• 1.1% of older adult stroke survivors developed epilepsy in this study, of whom 12.9% developed refractory epilepsy, indicating that this population is particularly responsive to treatment.
• Over 85% of deaths in this population are not due to stroke or epilepsy.

Distinct White Matter Changes Associated With Cerebrospinal Fluid Amyloid-Β1-42 And Hypertension, Omar M. Al-Janabi, Christopher A. Brown, Ahmed A. Bahrani, Erin L. Abner, Justin M. Barber, Brian T. Gold, Larry B. Goldstein, Richard R. Murphy, Peter T. Nelson, Nathan F. Johnson, Leslie M. Shaw, Charles D. Smith, John Q. Trojanowski, Donna M. Wilcock, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults.

OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.

METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ_1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess …

Advancing Stroke Genomic Research In The Age Of Trans-Omics Big Data Science: Emerging Priorities And Opportunities, Mayowa Owolabi, Emmanuel Peprah, Huichun Xu, Rufus Akinyemi, Hemant K. Tiwari, Marguerite R. Irvin, Kolawole Wasiu Wahab, Donna K. Arnett, Bruce Ovbiagele

Epidemiology and Environmental Health Faculty Publications

Background—We systematically reviewed the genetic variants associated with stroke in genome-wide association studies (GWAS) and examined the emerging priorities and opportunities for rapidly advancing stroke research in the era of Trans-Omics science.

Methods—Using the PRISMA guideline, we searched PubMed and NHGRI- EBI GWAS catalog for stroke studies from 2007 till May 2017.

Results—We included 31 studies. The major challenge is that the few validated variants could not account for the full genetic risk of stroke and have not been translated for clinical use. None of the studies included continental Africans. Genomic study of stroke among Africans presents …

Risk Of Incident Clinical Diagnosis Of Alzheimer's Disease-Type Dementia Attributable To Pathology-Confirmed Vascular Disease, Hiroko H. Dodge, Jian Zhu, Randy Woltjer, Peter T. Nelson, David A. Bennett, Nigel J. Cairns, David W. Fardo, Jeffrey A. Kaye, Deniz-Erten Lyons, Nora Mattek, Julie A. Schneider, Lisa C. Silbert, Chengjie Xiong, Lei Yu, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Smart Data Consortium

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD).

METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with …

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …

Research Methods In Occupational Health Psychology, Irvin Sam Schonfeld, Chu-Hsiang Chang

Publications and Research

http://www.springerpub.com/occupational-health-psychology.html

Occupational Health Psychology (OHP) is a rapidly expanding interdisciplinary field that focuses on the science and practice of psychology in promoting and developing workplace health- and safety-related initiatives. This comprehensive text for undergraduate and graduate survey courses is the first to encompass a wide range of key issues in OHP. It draws from the domains of psychology, public health, preventive medicine,nursing, industrial engineering, law, and epidemiology to focus on the theory and practice of protecting and promoting the health, well-being, and safety of individuals in the workplace and improving the quality of work life.

The text addresses key psychosocial …

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

Risk Of Medication Overuse Headache Across Classes Of Treatments For Acute Migraine, Kristian Thorlund, Christina Sun-Edelstein, Eric Druyts, Steve Kanters, Shanil Ebrahim, Rahul Bhambri, Elodie Ramos, Edward Mills, Michel Lanteri-Minet, Stewart Tepper

Dartmouth Scholarship

Background: The most commonly prescribed medications used to treat migraine acutely are single analgesics, ergots, opioids, and triptans. Due to varying mechanisms of action across drug classes, there is reason to believe that some classes may be less likely than others to elicit Medication Overuse Headache (MOH) than others. We therefore aimed to determine whether certain classes of acute migraine drugs are more likely to elicit MOH than others.

Methods: A comprehensive systematic literature was conducted to identify studies of varying designs that reported on MOH within the considered treatment classes. Only studies that reported MOH according to the International …

Diabetes Is Associated With Cerebrovascular But Not Alzheimer's Disease Neuropathology, Erin L. Abner, Peter T. Nelson, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Randall L. Woltjer, Nigel J. Cairns, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Kamal Masaki, Suzanne L. Tyas, David A. Bennett, Julie A. Schneider, Zoe Arvanitakis

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood.

METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of >1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression.

RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P < .0001), specifically lacunes (OR = 1.71, P < .0001), but not Alzheimer's disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer's neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone.

DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer's disease pathology, and at least some of diabetes' relationship to …

Als Mutant Sod1 Interacts With G3bp1 And Affects Stress Granule Dynamics, Jozsef Gal, Lisha Kuang, Kelly R. Barnett, Brian Z. Zhu, Susannah C. Shissler, Konstantin V. Korotkov, Lawrence J. Hayward, Edward J. Kasarskis, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Mutations in Cu/Zn superoxide dismutase (SOD1) are responsible for approximately 20 % of the familial ALS cases. ALS-causing SOD1 mutants display a gain-of-toxicity phenotype, but the nature of this toxicity is still not fully understood. The Ras GTPase-activating protein-binding protein G3BP1 plays a critical role in stress granule dynamics. Alterations in the dynamics of stress granules have been reported in several other forms of ALS unrelated to SOD1. To our surprise, the mutant G93A SOD1 transgenic mice exhibited pathological cytoplasmic inclusions that co-localized with G3BP1-positive granules in spinal cord motor neurons. …

Accuracy Of Icd-9-Cm Codes By Hospital Characteristics And Stroke Severity: Paul Coverdell National Acute Stroke Program, Tiffany E. Chang, Judith H. Lichtman, Larry B. Goldstein, Mary G. George

Neurology Faculty Publications

Background—Epidemiological and health services research often use International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes to identify patients with clinical conditions in administrative databases. We determined whether there are systematic variations between stroke patient clinical diagnoses and ICD‐9‐CM codes, stratified by hospital characteristics and stroke severity.

Methods and Results—We used the records of patients discharged from hospitals participating in the Paul Coverdell National Acute Stroke Program in 2013. Within this stroke‐enriched cohort, we compared agreement between the attending physician's clinical diagnosis and principal ICD‐9‐CM code and determined whether disagreements varied by hospital characteristics (presence of a …

Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray

Pharmacology and Nutritional Sciences Faculty Publications

Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.

Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using …

Sex Disparities In Access To Acute Stroke Care: Can Telemedicine Mitigate This Effect?, Catherine Wolff, Amelia K. Boehme, Karen Albright, Tzu-Ching Wu, Michael Mullen, Sean Savitz, Charles Branas, James Grotta, Brendan Carr

Journal of Health Disparities Research and Practice

Background: Women have more frequent and severe ischemic strokes than men, and are less likely to receive treatment for acute stroke. Primary stroke centers (PSCs) have been shown to utilize treatment more frequently. Further, as telemedicine (TM) has expanded access to acute stroke care we sought to investigate the association between PSC, TM and access to acute stroke care in the state of Texas.

Methods: Texas hospitals and resources were identified from the 2009 American Hospital Association Annual Survey. Hospitals were categorized as: (1) stand-alone PSCs not using telemedicine for acute stroke care, (2) PSCs using telemedicine for acute stroke …