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Neuro-degenerative Diseases

Lorenzo Pini, Rosa Manenti, Maria Cotelli, Francesca B Pizzini, Giovanni B Frisoni, Michela Pievani
Non-invasive brain stimulation (NIBS) is emerging as a promising rehabilitation tool for a number of neurodegenerative diseases. However, the therapeutic mechanisms of NIBS are not completely understood. In this review, we will summarize NIBS results in the context of brain imaging studies of functional connectivity and metabolites to gain insight into the possible mechanisms underlying recovery. We will briefly discuss how the clinical manifestations of common neurodegenerative disorders may be related with aberrant connectivity within large-scale neural networks...
January 29, 2019: Neuro-degenerative Diseases
Xue Liang, Zhenyu Yin, Renyuan Liu, Hui Zhao, Sichu Wu, Jiaming Lu, Zhao Qing, Yongyue Wei, Qingxian Yang, Bin Zhu, Yun Xu, Bing Zhang
PURPOSE: (1) To investigate atrophy patterns of hippocampal subfield volume and Alzheimer's disease (AD)-signature cortical thickness in mild cognitive impairment (MCI) patients; (2) to explore the association between the neuropsychological (NP) and the brain structure in the MCI and older normal cognition group; (3) to determine whether these associations were modified by the apolipoprotein E (APOE) ε4 gene and cognitive status. METHODS: The FreeSurfer software was used for automated segmentation of hippocampal subfields and AD-signature cortical thickness for 22 MCI patients and 23 cognitive normal controls (NC)...
January 23, 2019: Neuro-degenerative Diseases
Spyros Papapetropoulos, Wenlei Liu, Sridhar Duvvuri, Kathleen Thayer, David L Gray
BACKGROUND: PF-06412562 is a moderately potent, highly selective oral D1/D5 dopamine receptor partial agonist. OBJECTIVE: To study the efficacy and safety of a single, oral, split dose of PF-06412562 in patients with Parkinson's disease. METHODS: Following overnight levodopa (L-dopa, Sinemet®) washout, subjects received a single dose of levodopa in open-label period 1. Periods 2 and 3 had a double-blinded, sponsor-open, randomized, 2-way cross-over, placebo-controlled design, during which subjects were randomized to PF-06412562 30 mg (+ 20 mg 4 h later) or placebo...
November 19, 2018: Neuro-degenerative Diseases
Elisabetta Zucchi, Roberta Bedin, Antonio Fasano, Nicola Fini, Annalisa Gessani, Marco Vinceti, Jessica Mandrioli
BACKGROUND: Patients presenting with upper motor neuron (UMN) signs may widely diverge in prognosis, ranging from amyotrophic lateral sclerosis (ALS) to primary lateral sclerosis (PLS) and hereditary spastic paraplegia (hSP). Neurofilaments are emerging as potential diagnostic and prognostic biomarkers for ALS, but the diagnosis of UMN syndromes still relies mostly on clinical long-term observation and on familiarity or genetic confirmation. OBJECTIVES: To test whether phosphorylated neurofilament heavy chain (pNfH) may discriminate different UMN syndromes at diagnosis and to test their prognostic role among these diseases...
November 14, 2018: Neuro-degenerative Diseases
Frederic Sampedro, Juan Marín-Lahoz, Saul Martínez-Horta, Javier Pagonabarraga, Jaime Kulisevsky
The role of cerebrospinal fluid (CSF) biomarkers such as CSF α-synuclein and CSF tau in predicting cognitive decline in Parkinson's disease (PD) continues to be inconsistent. Here, using a cohort of de novo PD patients with preserved cognition from the Parkinson's Progression Markers Initiative (PPMI), we show that the SNCA rs356181 single nucleotide polymorphism (SNP) modulates the effect of these CSF biomarkers on cortical thinning. Depending on this SNP's genotype, cortical atrophy was associated with either higher or lower CSF biomarker levels...
October 18, 2018: Neuro-degenerative Diseases
Cristiane M Ida, Malinda L Butz, Patrick A Lundquist, D Brian Dawson
BACKGROUND: European studies identified the C9orf72 repeat expansion as the most frequent genetic alteration in patients with Huntington disease (HD)-like phenotypes but negative HD genetic testing. OBJECTIVE: To investigate C9orf72 repeat expansion frequency in individuals tested for HD in a North American tertiary referral laboratory. METHODS: Three hundred and seventy-three cases (115 positive and 258 negative for HD) were evaluated by genotyping PCR, with follow-up Southern blot and 5' repeat methylation status assessment by combined repeat-primed and methylation-specific PCR in a subset...
October 18, 2018: Neuro-degenerative Diseases
Jon Adams, Michael Lee, Wenbo Peng
BACKGROUND: Despite a lack of evidence of clinical efficacy for complementary and alternative medicine (CAM) use in amyotrophic lateral sclerosis (ALS), these medicines remain popular around the world. OBJECTIVE: To examine the prevalence and cost of CAM use in ALS and CAM users' profile, decision-making, information seeking, and disclosure among ALS patients. METHODS: A comprehensive literature search was conducted of MEDLINE, CINAHL/SCOPUS, and AMED databases from their inception to April 2018...
2018: Neuro-degenerative Diseases
Anthoula C Tsolaki, Olympia Gatzima, Makrina Daniilidou, Eutuxia Lazarou, Panagiotis D Bamidis, Eleni Verykouki, Zafiroura Iakovidou-Kritsi, Magda Tsolaki
BACKGROUND: Apolipoprotein E ε4 allele (APOEε4) is a major genetic risk factor for Alzheimer's disease (AD). APOEε4 carriers have a higher risk of cognitive impairment and AD in a gene dose-dependent manner. The above notion is investigated in the Greek population. METHODS: A sample of 1,703 subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc...
2018: Neuro-degenerative Diseases
Leyre Martinez-Merino, Marina Iridoy, Arkaitz Galbete, Miren Roldán, Adriana Rivero, Blanca Acha, Pilar Irún, Cecilia Canosa, Miguel Pocoví, Maite Mendioroz, Ivonne Jericó
BACKGROUND: The development of biomarkers for use in diagnosing, monitoring disease progression and analyzing therapeutic trials response in amyotrophic lateral sclerosis (ALS) is essential. OBJECTIVE: The aim of this study was to identify inflammatory factors in plasma or cerebrospinal fluid (CSF) from patients with ALS with particular attention to specific markers of microglia activation as chitotriosidase (ChT) and chemokine (C-C motif) ligand 18 (CCL18) to determine its potential as ALS biomarkers...
2018: Neuro-degenerative Diseases
Sun Hwa Lee, Eun Jin Yang
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes selective motor neuron cell death and accompanying skeletal muscle atrophy and structural deformities. In both patients with ALS and animal models, there appears to be spinal cord and muscle pathology. This pathology can be modeled in hSOD1G93A mice, which have a point mutation in the gene for superoxide dismutase 1. Similar to patients with ALS, hSOD1G93A mice present hepatic abnormalities and lymphocytic infiltration in the liver...
2018: Neuro-degenerative Diseases
Jason A Chen
BACKGROUND: Recent advances in genetics have provided insights into important inherited causes of Parkinson's disease (PD), but the underlying biological mechanisms are still incompletely understood. Gene expression studies have pointed toward the dysregulation of neuroinflammation, mitochondrial function, and protein degradation pathways. OBJECTIVE: We aimed to identify groups of dysregulated genes in PD. METHODS: In order to increase statistical power and control for potential confounders, we re-analyzed transcriptomic data from PD patients and model systems, integrating additional genomic data using a systems biology approach...
2018: Neuro-degenerative Diseases
Samuel Iddi, Dan Li, Paul S Aisen, Michael S Rafii, Irene Litvan, Wesley K Thompson, Michael C Donohue
Parkinson's disease is the second most common neurological disease and affects about 1% of persons over the age of 60 years. Due to the lack of approved surrogate markers, confirmation of the disease still requires postmortem examination. Identifying and validating biomarkers are essential steps toward improving clinical diagnosis and accelerating the search for therapeutic drugs to ameliorate disease symptoms. Until recently, statistical analysis of multicohort longitudinal studies of neurodegenerative diseases has usually been restricted to a single analysis per outcome with simple comparisons between diagnostic groups...
2018: Neuro-degenerative Diseases
Sayed-Hamidreza Mozhgani, Hamid Reza Jahantigh, Houshang Rafatpanah, Narges Valizadeh, Asadollah Mohammadi, Samira Basharkhah, Seyed Abdolrahim Rezaee
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neuroinflammatory disease related to human T lymphotropic virus type 1 (HTLV-1) infection. Interferon type III (IFN-λ), which includes IL28, IL29, and IL28R, and affects the outcome of viral infections, might be complicated in the progression of HAM/TSP. Here, we investigated the host-virus interactions in the manifestation of HAM/TSP, using IL28B, IL29, IL28R, HTLV-1 Tax, HTLV-1 basic leucine zipper factor (HBZ), and proviral load (PVL)...
2018: Neuro-degenerative Diseases
Yusen Qiu, Ling Xin, Yuyao Wang, Yanyan Yu, Keji Zou, Qian Zhou, Yunqing Chen, Shuyun Chen, Min Zhu, Daojun Hong
BACKGROUND: Adult adrenomyeloneuropathy (AMN) is caused by mutations in the ABCD1 gene. Some pure AMN patients develop cerebral demyelination late in life. However, hypoplasia and agenesis of the corpus callosum (CC) has never been reported in AMN patients. OBJECTIVE: To describe a new clinical variant of AMN that is possibly caused by a novel ABCD1 gene mutation. METHODS: A total of 10 members in an X-linked inherited family were examined...
2018: Neuro-degenerative Diseases
Will Lee, David R Williams, Andrew Evans
BACKGROUND: Interference refers to learned associations and established behaviors "interfering" with response to new material. It forms a core pillar of executive functions, which are commonly affected in Parkinson's disease (PD). Cognitive interference test (CIT) forms part of a smartphone application designed for ambulatory assessment in PD. OBJECTIVE: The aims of this study were to establish that CIT could effectively demonstrate interference and would perform comparably to the Stroop Color-Word Test Victoria version (VST) despite PD-related motor impairment...
2018: Neuro-degenerative Diseases
Ane Miren Crespo Cuevas, Lourdes Ispierto, Dolores Vilas, Anna Planas, Albert Planas, Irina Isern, Josep Sanchez, Josep De Haro, Ramiro Alvarez
BACKGROUND: Olfactory dysfunction is common in Parkinson's disease (PD). The characteristics of the hyposmia in PD have not been well defined. OBJECTIVE: To characterize the pattern of the olfactory deficit in PD and in other non-neurodegenerative aetiologies of hyposmia. METHODS: We evaluated 36 PD patients, 20 patients with hyposmia secondary to acute respiratory infection (ARI), and 19 patients with hyposmia secondary to traumatic brain injury (TBI)...
2018: Neuro-degenerative Diseases
Zhong-Ying Gong, Gao-Peng Lv, Li-Na Gao, Yi Lu, Jie Guo, Da-Wei Zang
BACKGROUND: There are no reliable biomarkers that could evaluate the disease burden in amyotrophic lateral sclerosis (ALS). OBJECTIVES: The aim of our study is to evaluate the changes in cerebrospinal fluid (CSF) and serum neurofilament subunit L (NF-L) in patients with ALS and to analyze the correlations between the levels of NF-L and clinical parameters. METHOD: CSF and serum samples were obtained from 80 ALS patients and 40 controls. The levels of NF-L in CSF and serum were assessed, and disease progression parameters including duration, revised ALS Functional Rating Scale (ALSFRS-r) score, disease progression rate (DPR), upper motor neuron (UMN) score, and survival were analyzed by registered neurologists...
2018: Neuro-degenerative Diseases
Ismini C Mainta, Sara Trombella, Silvia Morbelli, Giovanni B Frisoni, Valentina Garibotto
BACKGROUND: A corollary of the reserve hypothesis is that what is regarded as pathological cortical metabolism in patients might vary according to education. OBJECTIVE: The aim of this study is to assess the incremental diagnostic value of education-adjusted over unadjusted thresholds on the diagnostic accuracy of FDG-PET as a biomarker for Alzheimer disease (AD). METHODS: We compared cortical metabolism in 90 healthy controls and 181 AD patients from the Alzheimer Disease Neuroimaging Initiative (ADNI) database...
2018: Neuro-degenerative Diseases
Daniela Vidinská, Petra Vochozková, Petra Šmatlíková, Taras Ardan, Jiří Klíma, Štefan Juhás, Jana Juhásová, Božena Bohuslavová, Monika Baxa, Ivona Valeková, Jan Motlík, Zdenka Ellederová
BACKGROUND: Huntington disease (HD) is an incurable neurodegenerative disease caused by the expansion of a polyglutamine sequence in a gene encoding the huntingtin (Htt) protein, which is expressed in almost all cells of the body. In addition to small animal models, new therapeutic approaches (including gene therapy) require large animal models as their large brains are a more realistic model for translational research. OBJECTIVE: In this study, we describe phenotype development in transgenic minipigs (TgHD) expressing the N-terminal part of mutated human Htt at the age of 24 months...
2018: Neuro-degenerative Diseases
Nini Mao, Yunting Liu, Kewei Chen, Li Yao, Xia Wu
BACKGROUND: Multiple neuroimaging modalities have been developed providing various aspects of information on the human brain. OBJECTIVE: Used together and properly, these complementary multimodal neuroimaging data integrate multisource information which can facilitate a diagnosis and improve the diagnostic accuracy. METHODS: In this study, 3 types of brain imaging data (sMRI, FDG-PET, and florbetapir-PET) were fused in the hope to improve diagnostic accuracy, and multivariate methods (logistic regression) were applied to these trimodal neuroimaging indices...
2018: Neuro-degenerative Diseases
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