Nervous System Diseases Commons^™

Management Of Parkinson's Disease Psychosis: First-Line Antipsychotic Selection And Rationale For Continuing, Combining, Or Switching, Stuart H. Isaacson, Henry Nasrallah, Rajesh Pahwa, Gustavo Alva, Daniel Kremens, Stephen M. Stahl

Department of Neurology Faculty Papers

INTRODUCTION: The past decade has seen a paradigm shift in the evaluation and management of Parkinson's disease psychosis (PDP), with the first approval of an antipsychotic in the US in 2016. An evidence-based review by the Movement Disorder Society found pimavanserin and clozapine to be clinically useful, (low-dose) quetiapine to be possibly useful, and all other antipsychotics to be avoided due to motor worsening. Clozapine and quetiapine use can be limited by provoking Parkinson's disease (PD) nonmotor symptoms of somnolence and hypotension. Quetiapine may also be limited by its risk in cognitive impairment. Pimavanserin is not associated with these symptoms. …

Dynamic Dysregulation Of Retrotransposons In Neurodegenerative Diseases At The Single-Cell Level\, Wankun Deng, Citu Citu, Andi Liu, Zhongming Zhao

Faculty, Staff and Student Publications

Retrotransposable elements (RTEs) are common mobile genetic elements comprising ∼42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. We identify cell type marker RTEs in neurons, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells that are related to these diseases. The differential expression analysis reveals the landscape of dysregulated RTE expression, especially L1s, in excitatory neurons of multiple neurodegenerative diseases. …

Absence Of Motor Impairments Or Pathological Changes In Tmem230 Knockout Rats, Wenjuan Zhang, Hao Peng, Daihe Yang, Guohua Song, Juan He, Yun Zhou, Cao Huang, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson's disease (PD), which is the second most common neurodegenerative disorder, is characterized by progressive movement impairment and loss of midbrain dopaminergic neurons in the substantia nigra. Although mutations in TMEM230 are linked to familial PD, the pathogenic mechanism underlying TMEM230-associated PD remains to be elucidated. To explore the effect of TMEM230 depletion in vivo, we created TMEM230 knockout rats using CRISPR-Cas9 technology. TMEM230 knockout rats did not exhibit any core features of PD, including impaired motor function, loss of dopaminergic neurons in the substantia nigra, or altered expression of proteins related to autophagy, the Rab family, or vesicular trafficking. …

Effect Of Dosage On Severity Of Dysphagia In A Toxicological Rat Model Of Parkinson's Disease, Shivam Patel, Taylor Good, Nicholas Zanghi, Francois Gould

Rowan-Virtua Research Day

Parkinson’s Disease (PD) is a prevalent and devastating neurodegenerative disorder that causes progressively worsening motor symptoms affecting locomotor and oropharyngeal function. There is limited research in animal models on swallowing dysfunction in PD. To examine how neurodegeneration in PD produces progressive impairment in the oropharyngeal and locomotor processes, rotenone, a type II mitochondrial inhibitor, was injected into Lewis rat models to reproduce a parkinsonian phenotype. We hypothesized that the animal models injected with the rotenone will exhibit both oropharyngeal dysfunction and locomotor deficiency with an increased deficit that correlates with prolonged treatment. We utilized 18 rats receiving either 2.75 mg/kg …

Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. …

Retinal Thickness In Essential Tremor And Early Parkinson Disease: Exploring Diagnostic Insights, Claudio Terravecchia, Giovanni Mostile, Clara G Chisari, Cristina Rascunà, Roberta Terranova, Calogero E Cicero, Loretta Giuliano, Giulia Donzuso, Giorgia Sciacca, Antonina Luca, Pierre-Marie Preux, Joseph Jankovic, Mario Zappia, Alessandra Nicoletti

Faculty, Staff and Students Publications

BACKGROUND: Essential tremor (ET) represents a heterogeneous condition which may overlap with Parkinson disease (PD) even at early stages, by sharing some subtle clinical aspects. Longstanding ET demonstrated also higher risk of developing PD, especially with a Tremor-dominant (TD-PD) phenotype. Therefore, differential diagnosis between ET and early PD could be quite challenging. Optical coherence tomography (OCT) has been recognized as a reliable tool to assess the retina as a proxy of neurodegeneration. We aimed to explore the possible role of retinal assessment in differential diagnosis between ET and early PD.

METHODS: Macular layers and peripapillary retinal nerve fiber layer (RNFL) …

Parkinson's Disease And Other Alzheimer's Disease And Related Dementia Pathologies And The Progression Of Parkinsonism In Older Adults, Aron S Buchman, Lei Yu, Shahram Oveisgharan, Andrea R Zammit, Tianhao Wang, Joshua M Shulman, Veronique Vanderhorst, Sukrit Nag, David A Bennett

Faculty, Staff and Students Publications

BACKGROUND: The interrelationship of parkinsonism, Parkinson's disease (PD) and other Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD) pathologies is unclear.

OBJECTIVE: We examined the progression of parkinsonian signs in adults with and without parkinsonism, and their underlying brain pathologies.

METHODS: Annual parkinsonian signs were based on a modified Unified Parkinson's Disease Rating Scale. We used linear mixed effects models to compare the progression of parkinsonian signs in 3 groups categorized based on all available clinical evaluations: Group1 (never parkinsonism or clinical PD), Group2 (ever parkinsonism, but never clinical PD), Group3 (ever clinical PD). In decedents, we examined …

Altered Outer Retinal Structure, Electrophysiology And Visual Perception In Parkinson's Disease, Katie K N Tran, Pei Ying Lee, David I Finkelstein, Allison M Mckendrick, Bao N Nguyen, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

BACKGROUND: Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation.

OBJECTIVE: To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing.

METHODS: Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = …

Blood-Based Transcriptomic Biomarkers Are Predictive Of Neurodegeneration Rather Than Alzheimer's Disease, Artur Shvetcov, Shannon Thomson, Jessica Spathos, Ann-Na Cho, Heather M Wilkins, Shea J Andrews, Fabien Delerue, Timothy A Couttas, Jasmeen Kaur Issar, Finula Isik, Simranpreet Kaur, Eleanor Drummond, Carol Dobson-Stone, Shantel L Duffy, Natasha M Rogers, Daniel Catchpoole, Wendy A Gold, Russell H Swerdlow, David A Brown, Caitlin A Finney

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a growing global health crisis affecting millions and incurring substantial economic costs. However, clinical diagnosis remains challenging, with misdiagnoses and underdiagnoses being prevalent. There is an increased focus on putative, blood-based biomarkers that may be useful for the diagnosis as well as early detection of AD. In the present study, we used an unbiased combination of machine learning and functional network analyses to identify blood gene biomarker candidates in AD. Using supervised machine learning, we also determined whether these candidates were indeed unique to AD or whether they were indicative of other neurodegenerative diseases, such as …

Dancing Through Parkinson’S: Investigating The Impact Of Argentine Tango On Motor, Cognitive And Psychosocial Function, Suraj Pothineni, Fazal Choudhary

Rowan-Virtua Research Day

Background: People with Parkinson’s Disease (PD) undergo progressive motor, cognitive, and psychosocial symptoms, which decrease their quality of life (QOL). Adapted tango (AT) has recently emerged as a promising approach to ameliorating functional mobility, balance, and gait seen in people with PD.

Methods: A comprehensive literature review is conducted using databases such as PubMed, SCOPUS, and Embase. A wide variety of search terms are used, including but not limited to Parkinson’s disease, exercise, dance, tango, motor, cognitive, psychosocial effects, freezing of gait, and balance.

Results: People with PD who have undergone AT have improved in certain motor, cognitive and psychosocial …

Swallowing Disrupts Tongue-Jaw Coordination During Chewing In A Rat Model Of Parkinson's Disease, Meejan Palhang, N. Charles, Francois Gould

Rowan-Virtua Research Day

The primary motor symptoms of Parkinson’s disease, including bradykinesia, rigidity, and tremor, are associated with difficulties regulating transitions between motor behaviors due to basal ganglia dysfunction. Chewing and swallowing, which are disordered in most patients with Parkinson’s disease, are two complex motor behaviors which overlap in time and share some neuromuscular components. The objective of this study is to identify how Parkinson’s disease affects the coordination of chewing and swallowing. We hypothesize that as a result of impaired regulation of shift between motor patterns, chewing cycles that occur with a swallow will be more affected that chewing cycles occurring in …

The Role Of Food Accessibility In Weight Loss In A Rat Model Of Parkinson’S Disease, Anjali Kikkisetti, Nicole Charles, Francois Gould

Rowan-Virtua Research Day

Parkinson’s disease (PD) is a neurodegenerative disorder that causes a variety of motor and non-motor symptoms. The goal of this project was to understand whether the weight loss seen with Parkinson’s disease was due to the lack of being able to access the food because of the food placement or because of inability to chew the food due to degeneration of muscles required for chewing food. Both treatment groups, Adjusted Diet and Unadjusted Diet, lost weight after injections started, whereas control weights were stable throughout the experiment. There is no statistically significant difference in weight loss between adjusted and unadjusted …

Characterization Of Retinal Function And Structure In The Mptp Murine Model Of Parkinson's Diseasecharacterization Of Retinal Function And Structure In The Mptp Murine Model Of Parkinson’S Disease, Katie K N Tran, Vickie H Y Wong, Jeremiah K H Lim, Ali Shahandeh, Anh Hoang, David I Finkelstein, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson's disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, …

Systematic Literature Review Of Quetiapine For The Treatment Of Psychosis In Patients With Parkinsonism, Jack J. Chen, Henry Hua, Lilian Massihi, Ivan Portillo, Azita Alipour, William Ondo, Khashayar Dashtipour

Library Articles and Research

Objective:

The purpose of this article was to determine the efficacy and tolerability of quetiapine compared with placebo or other interventions for psychosis in parkinsonism.

Methods:

Participants with a diagnosis of parkinsonism participated in randomized controlled trials (RCTs) investigating the efficacy and tolerability of quetiapine for psychotic symptoms within a defined follow-up period. The authors conducted searches on PubMed, Cochrane Controlled Register of Trials, and EMBASE for articles published from January 1991 to October 2017. Study methodology and patient- and treatment-level data were independently extracted and summarized by using descriptive statistics. Studies underwent quality assessment for risk of bias.

Results: …

Objectively Measuring Effects Of Electro-Acupuncture In Parkinsonian Rhesus Monkeys, Rui Zhang, Anders H. Andersen, Peter A. Hardy, Eric Forman, April Evans, Yi Ai, Jin Yue, Guihua Yue, Don M. Gash, Richard Grondin, Zhiming Zhang

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Acupuncture has increasingly been used as an alternative therapy for treatment of Parkinson’s disease (PD). However, the efficacy of acupunture for PD still remains unclear. The present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (EA) and brain activity in nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations. All animals were evaluated for behavior and phMRI responses under normal, parkinsonian, parkinsonian with EA treatment and parkinsonian after EA treatment conditions. Stable parkinsonian features were observed …

Administration Of Electroconvulsive Therapy For Depression Associated With Deep Brain Stimulation In A Patient With Post-Traumatic Parkinson's Disease: A Case Study, Miles G. Cunningham, Golnaz Yadollahikhales, Gordana Vitaliano, Craig Van Horne

Neurosurgery Faculty Publications

Background: Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression.

Case Presentation: The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. …

Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. My thesis work has focused on this "cause and/or …

Tetrahydroisoquinoline Neurotoxins In Parkinson Disease, Michael G. Decuypere

Theses and Dissertations (ETD)

The goal of this dissertation work was to (1) determine the distribution of several tetrahydroisoquinoline (TIQ) derivatives in rodent, normal human and Parkinson disease (PD) brain, (2) quantify the levels of these TIQ derivatives in common food sources in an effort to link specific food intake patterns with the development of PD and (3) examine the neurotoxicity of select TIQ derivatives in human dopaminergic cell culture. The TIQs are a family of monoamine alkaloids that share structural homology with 1-methyl-4-phenyl-1,2,3,6-tetrahyrdropyridine (MPTP), can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell …

A National Estimate Of The Cost Of Illness In Parkinson's Disease Using Retrospective Data Analysis, Katherine Anderson

Theses and Dissertations (ETD)

The purpose of this study was to estimate the cost of illness of Parkinson’s disease in the United States. Direct medical expenditures, with the exception of nursing home costs, were estimated using data from the 1999-2003 Medical Expenditures Panel Survey Household Component (MEPS-HC). Nursing home costs were estimated using the Medical Expenditures Panel Survey Nursing Home Component (MEPS-NHC). Indirect costs for lost productivity due to missed work or bed-days (morbidity) were estimated using the MEPS-HC and the Bureau of Labor Statistics (BLS). Indirect costs for lost productivity due to death (mortality) were estimated using the National Vital Statistics System.

Direct …