Nervous System Diseases Commons^™

Survivin And Caspases Coordinate Proteolytic Cleavage Of The Saga Chromatin Modifying Complex, Elinor Harrison, Alejandro Damian, Cj Talton

Medical Student Research Symposium

Title: Survivin and Caspases Coordinate Proteolytic Cleavage of the SAGA Chromatin Modifying Complex

Elinor Harrison¹, Alejandro Damian¹, CJ Talton¹, Jelly H Soffers¹, Abudu I Bello¹, Kara M Costanzo¹, Joe Bean¹, Ryan D Mohan¹

¹Wayne State University School of Medicine

Background: The Spt Ada Gcn5 Acetyltransferase (SAGA) chromatin modifying complex is a critical regulator of gene expression. Mutation or stoichiometric imbalance of SAGA subunits leads to a spectrum of diseases in model organisms and in humans, including neurodegeneration. SAGA contributes to gene activation through coordinated …

Feeding The Mind: Dietary Consumption And Neural Aging, Bhavani Tuppale

Senior Theses

Neural aging is the process of physiological decline in the brain and increased vulnerability to neurodegenerative diseases. Neurodegenerative diseases such as Alzheimer’s disease are associated with aging and the interaction of genetics and lifestyle choices. Previous research studies have connected Alzheimer’s disease with dysfunction in the metabolic system. To combat age-associated dysfunctions in the metabolic system, research studies propose using the ketogenic diet, which utilizes ketone bodies as an energy source instead of glucose. The thesis analyzes literature on the effect of neural aging on various model organisms, how a ketogenic diet affects aging model organisms, and how aging and …

Using Diffusion Mri To Relate Hippocampal Subfield Microstructure To Delayed Verbal Memory In Cognitively Intact Individuals At Genetic Risk For Developing Alzheimer's Disease, Jennapher Lingo Vangilder, Andrew Hooyman, Sasha Hakhu, Kurt G. Schilling, Leland S. Hu, Yuxiang Zhou, Richard J. Caselli, Leslie C. Baxter, Scott C. Beeman

Physical Therapy Faculty Articles and Research

Intervention to delay the onset of Alzheimer's disease (AD) is an important treatment strategy but detecting at-risk individuals before significant disease progression remains challenging. This study evaluates the relationship between hippocampal microstructure and verbal cognition in cognitively intact older adults, focusing on the differences between APOΕ ε4 allele carriers and noncarriers. Participants (n = 41 noncarriers, 33 carriers) over 60 years old (mean ± SD: carriers 71 ± 6.6; noncarriers 71 ± 6.4 years) underwent diffusion-weighted magnetic resonance imaging (dMRI) and volumetric assessments. We assessed hippocampal structure, including microstructure, using Neurite Orientation Dispersion and Density Imaging (NODDI), diffusion tensor …

Multi-Modal Tensor Fusion For Alzheimer’S Disease Recognition, Mason Li, Tiffany Le, Jiajing Huang, Yuxin Wen

Engineering Faculty Articles and Research

Accurate and early diagnosis of Alzheimer’s disease (AD) is critical for effective intervention, disease monitoring, and patient care. Traditional diagnostic approaches rely on a single modality, such as clinical assessments, neuroimaging, or genetic markers, which may fail to capture the complex, multifaceted nature of AD. Multimodal learning has therefore been explored to integrate complementary information across data sources. However, conventional fusion strategies, including early feature concatenation and late decision-level fusion, often model modalities independently and fail to capture high-order cross-modal interactions. To address these limitations, we propose a multimodal tensor fusion network (MTFN) that integrates heterogeneous data sources, including visual …

Transcranial Alternating Current Stimulation As An Adjuvant For Nonfluent Aphasia: A Proof-Of-Concept Study, Lynsey M. Keator, Lisa Johnson, Roger Newman-Norlund, Kyler Spell, Samaneh Nemati, Leigh Ann Spell, Dirk B. Den Ouden, Christopher Rorden, Julius Fridriksson

Department of Speech-Language Pathology Faculty Papers

Effective rehabilitation tools are essential for improving language outcomes in chronic aphasia. Speech entrainment is a behavioral treatment that has shown promise in enhancing speech output in nonfluent aphasia, potentially by acting as an external mechanism to synchronize anterior and posterior language regions in the left hemisphere. Transcranial alternating current stimulation has been hypothesized to enhance functional connectivity between brain regions by amplifying endogenous oscillations. This proof-of-concept study explored whether high-definition tACS (HD-tACS) could improve speech fluency in nonfluent aphasia when paired with speech entrainment. In a double-blind, pseudorandomized study, 1 mA of HD-tACS at 7 Hz was applied to …

Discordance Between Actual And Perceived Balance Ability Relates To Quality Of Life And Global Cognition In A Clinical Sample Of Parkinson Patients, Daniel S. Peterson, Jason K. Longhurst, Franziska Albrecht, Joanna Weller, Jennifer Vasquez, Myassar Zarif, Mark Gudesblatt, Andrew Hooyman

Physical Therapy Faculty Articles and Research

Background

Objective

Methods

Contribution Of G4 Structure To Alzheimer’S Disease And Tau Pathology, Lena Michaela Kallweit

Electronic Theses and Dissertations

The occurrence of Alzheimer’s Disease (AD) is rapidly increasing as our global population ages. With the majority of therapeutic drugs in the last couple of decades failing clinical trials, new molecular targets are needed to combat the expected influx of new AD cases. AD pathogenesis is associated with abnormal protein aggregation, characterized in part by intracellular accumulation of hyperphosphorylated tau (p-tau) in neurofibrillary tangles (NFTs). RNA has been identified as a major non-proteinaceous component of NFTs and has been implicated as an active cofactor in tau aggregation and spread. Recent work has shown that aggregates from AD brains contain almost …

Disrupted Nuclear Function And Nucleocytoplasmic Transport In Parkinson’S Disease, Ichiro M. Matoba

The Cardinal Edge

No abstract provided.

Editorial: Clinical Imaging, Neurophysiological, Neuropathology And Neuroethics Studies On Disorders Of Consciousness, Coma Mechanisms, And Theories Of Consciousness: A Unifying Attempt, Diego Iacono, Manuel Trachsel, Thanh Phan, Charlène Aubinet

Department of Neurology Faculty Papers

No abstract provided.

Biomarkers In Alzheimer's Disease Clinical Trials: 2025, Amanda M. Leisgang Osse, Yadi Zhou, Jefferson W. Kinney, Andrew Hooyman, Ayan Sengupta, Jorge Fonseca, Aaron H. Burstein, Laura Nisenbaum, Howard M. Fillit, Feixiong Cheng, Jeffrey L. Cummings

Physical Therapy Faculty Articles and Research

Biomarkers play an important role in Alzheimer's disease (AD) clinical trials in several contexts of use, including defining trial eligibility and serving as outcome measures. Utilizing clinicaltrials.gov, a registry of clinical trials, we assessed biomarker usage across all active AD disease-targeted therapeutic (DTT) trials. Biomarkers are widely used in AD DTT trials, with 84% including a fluid, imaging, and/or digital biomarker, either as an inclusion criterion or as an outcome measure. In DTT trials, biomarkers were included in 83% of Phase 3 trials, 91% of Phase 2 trials, and 72% of Phase 1 trials. Biomarkers were used for trial inclusion …

Diagnostic Accuracy Of Cerebral Amyloid Angiopathy Criteria In The First Pathologically Confirmed Thai Cohort: A Pilot Study, Thanapoom Taweephol, Thachamai Smitasiri, Thanakit Pongpitakmetha, Sekh Thanprasertsuk, Anand Viswanathan

Chulalongkorn Medical Journal

Background: The gold standard for diagnosing cerebral amyloid angiopathy (CAA), full brain post-mortem examination, is rarely performed. Current diagnostic criteria, primarily based on clinico-radiological features, were developed from Western populations and may have limited applicability to Asian populations.

Objective: We aimed to evaluate the accuracy of current diagnostic criteria and examine the clinico-radiological characteristics of Thai CAA patients.

Methods: Brain histopathological specimens from patients with clinical symptoms of CAA who underwent neurosurgical procedures, including intracerebral hemorrhage (ICH) evacuation, between 2011 and 2021 at King Chulalongkorn Memorial Hospital, Thailand, were reviewed. Patient characteristics and clinical events for each individual were retrospectively …

Epidemiology Of Healthcare-Associated Ventriculitis And Meningitis (Hcavm) And Community-Acquired Meningitis/Encephalitis And Evaluation Of An Off-Label Pcr Panel For Hcavm Diagnosis, Jaime Nassur, Katarina Schnell, Christine Dolon, Laura Walters, Devin Weber, Matthew Pettengill

Department of Medicine Faculty Papers

Healthcare-associated ventriculitis and meningitis (HCAVM) is associated with high morbidity and mortality, but rapid diagnostic tests intended to cover microorganisms that typically cause HCAVM are not commercially available. We sought to evaluate the etiology of HCAVM compared to community-acquired meningitis/encephalitis (CAME) at our healthcare system, and to study the utility of repurposing a multiplex molecular panel intended for positive blood cultures for HCAVM cases. Our epidemiologic review demonstrated that HCAVM cases were primarily caused by bacteria and fungi also associated with bloodstream infections, in contrast with CAME cases, which were primarily caused by herpesviruses and Cryptococcus. Eighty-two cerebrospinal fluid …

Increasing Physical Activity In Moderate-Severe Traumatic Brain Injury: Protocol For A Two-Stage Randomized Controlled Trial Of A Remote, Mhealth-Enhanced Intervention, Tessa Hart, Monica Vaccaro, Lauren Krasucki, Inna Chervoneva, Amanda Rabinowitz

Moss-Magee Rehabilitation Papers

OBJECTIVE: Protocol for randomized controlled trial (RCT) examining effects of novel, remotely delivered intervention (called GetUp&Go) to increase physical activity (PA) in chronic, moderate-severe traumatic brain injury (msTBI), including a mobile health (mHealth) component.

DESIGN: RCT (Clinicaltrials.gov NCT06028334) with 1:1 randomization to 10 weeks of immediate treatment (IT) or waitlist (WL), with primary outcome measured at 10 weeks. A second randomization to 10 weeks of continued mHealth support vs. no treatment will allow for examination of effects of mHealth on maintenance of treatment gains.

PARTICIPANTS: 70 community-dwelling adults ≥6 months post msTBI; medically cleared and physically/ cognitively able to participate; …

Incidence And Predictors Of Encephalopathy In Patients Admitted With Lower Urinary Tract Infections: A Nationwide Analysis, Purva Shah, Shiamak Cooper, Ali Jaan, Basil George Verghese

Advances in Clinical Medical Research and Healthcare Delivery

Background. There are no large-scale study assessing the incidence and predictors of encephalopathy in patients with UTI. Also, there is a lack of data on encephalopathy outcomes in patients hospitalized with UTI. We aim to evaluate the incidence, predictors, and impact of encephalopathy on the outcomes of LUTI hospitalizations

Methods. Retrospective cohort study using data from the National Inpatient Sample (NIS) database (2017–2020). We included adult patients (aged ≥18 years) admitted with a principal diagnosis of lower urinary tract infection (LUTI), utilizing the International Classification of Diseases, Tenth Revision, and Clinical Modifications (ICD-10- CM) codes. Multivariate logistic and linear regression …

Recurrent Miller Fisher Syndrome: A Case Report, Larry Vernier, Griffin B. Gilmore, Kelsey Van Housen, Xiao C. Zhang

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Guillain-Barré syndrome can manifest with progressive paralysis, requiring careful monitoring and treatment with steroids or intravenous (IV) immunoglobin. While this disease can be devastating and require intensive care unit level of care, there are few incidences of relapses.

CASE REPORT: A 67-year-old man with a past medical history of Miller Fisher syndrome variant of Guillain-Barré syndrome, with complete recovery, presented to the emergency department (ED) with ataxia, ophthalmoplegia, dysphonia, and ambulatory dysfunction. The patient noticed his neurologic symptoms after waking up, and he presented to the ED with physical examination positive for difficulty with upward gaze, mild right lower …

N-Acetylcysteine Is Associated With Changes In Functional Connectivity In Patients With Parkinson's Disease, Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Faezeh Vedaei, Emily Navarreto, Monisha Gupta, Alicia Steinmetz, Anthony J. Bazzan, Feroze Mohamed, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

INTRODUCTION: This study assessed the changes in functional connectivity from resting functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) given N-Acetylcysteine (NAC), the prodrug to L-cysteine and a precursor to the natural biological antioxidant glutathione (GSH). The aim of this study was to determine whether NAC is associated with changes in functional connectivity, particularly in the basal ganglia, and improvements in Parkinson's symptoms.

METHODS: Forty-four patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of …

Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic …

Nature-Based Approaches To Dementia, Cognitive Impairment, And Caregiver Well-Being: A Scoping Review Of Gardening And Therapeutic Strategies, Mary Dioise Ramos, Marcy Purnell, Jolie Harris, Gloria Giarratano

School of Nursing Faculty Publications

Background: Dementia is a growing global health concern, with behavioral and psychological symptoms (BPSD) contributing significantly to diminished quality of life and caregiver burden. Non-pharmacological interventions, such as gardening and nature-based therapies, are increasingly recognized for their therapeutic potential. Objectives: This scoping review aimed to: (1) map existing evidence on gardening and garden-based interventions for individuals with dementia; (2) assess impacts on caregivers; (3) identify mechanisms of benefit; and (4) summarize effective design and implementation strategies. Methods: Following Joanna Briggs Institute methodology and PRISMA-ScR guidelines, a comprehensive search was conducted across five databases. Studies were screened using Covidence. Inclusion criteria …

Clinical, Imaging And Blood Biomarker Outcomes In A Phase 3 Clinical Trial Of Tau Aggregation Inhibitor Hydromethylthionine Mesylate In Mild Cognitive Impairment And Mild To Moderate Dementia Due To Alzheimer’S Disease, Claude Wischik, Richard G. Stefanacci, Peter Bentham, Serge Gauthier, Henrik Zetterberg, Gordon Wilcock, Lutz Froelich, Alistair Burns, Emer Macsweeney, Clive Ballard, Jin-Tai Yu, Tay Siew Choon, Vahe Asvatourian, Natalia Muehlemann, Jan Priel, Karin Kook, Tenecia Sullivan, Diane Downie, Sonya Miller, Carol Pringle, John Storey, Tom Baddeley, Charles R Harrington, Lewis Penny, Mohammad Arastoo, Roger Staff, Anca-Larisa Sandu, Helen Shiells, Serena Lo, Nafeesa Nazlee, Emily Evans, Claire Hull, Bjoern Schelter

College of Population Health Faculty Papers

BACKGROUND: Hydromethylthionine mesylate (HMTM) targets tau pathology and has tau-independent symptomatic activity.

OBJECTIVES: To evaluate the safety and efficacy of HMTM in participants with mild cognitive impairment (MCI) and mild to moderate dementia due to Alzheimer's disease (AD).

SETTING: 82 centres in Canada, European Union, United Kingdom and United States of America.

PARTICIPANTS: A total of 598 amyloid β-PET positive participants were included; 44% (263) met clinical criteria for MCI due to Alzheimer's disease and 56% (335) were diagnosed with mild to moderate dementia due to AD.

INTERVENTION: HMTM 16 mg/day and 8 mg/day were compared with methylthioninium chloride (MTC) …

Plans4care, A Web Application Providing Caregivers Personalized Solutions To Manage Dementia-Related Care Challenges: Proof Of Concept And Efficacy Trial, Laura N. Gitlin, Eric Jutkowitz, Catherine V. Piersol, Sokha Koeuth, Taylor Sivori, Melinda J. Webster, Rachel N. Barnett, David L. Roth

Department of Occupational Therapy Faculty Papers

OBJECTIVE: Few dementia caregivers have access to evidence-based support programs. Web applications (app) may address this gap. Plans4Care, a web app, provides caregivers with on-demand personalized solutions to address care challenges. We present results of a proof-of-concept study and describe a trial protocol to test efficacy.

METHODS: To use Plans4Care, caregivers respond to brief onboarding questions, assess dementia patients' cognitive function, identify care challenges, and generate "action plans" (personalized strategies). Telehealth sessions with dementia-trained care advisors are available. A proof-of-concept study evaluated a clickable prototype using standardized technology scales to determine if >75 % scored positively on four criteria (acceptability, …