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https://www.readbyqxmd.com/read/29138080/muscarinic-receptor-subtype-distribution-in-the-central-nervous-system-and-relevance-to-aging-and-alzheimer-s-disease
#1
REVIEW
E P Lebois, C Thorn, J R Edgerton, M Popiolek, S Xi
Muscarinic acetylcholine receptors (mAChRs) are G proteincoupled receptors (GPCRs) that mediate the metabotropic actions of acetylcholine (ACh). There are five subtypes of mAChR, M1 - M5, which are expressed throughout the central nervous system (CNS) on numerous cell types and represent promising treatment targets for a number of different diseases, disorders, and conditions of the CNS. Although the present review will focus on Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), a number of conditions such as Parkinson's disease (PD), schizophrenia, and others represent significant unmet medical needs for which selective muscarinic agents could offer therapeutic benefits...
November 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29129681/decreased-sirtuin-deacetylase-activity-in-lrrk2-g2019s-ipsc-derived-dopaminergic-neurons
#2
Andrew J Schwab, Samantha L Sison, Michael R Meade, Katarzyna A Broniowska, John A Corbett, Allison D Ebert
Mitochondrial changes have long been implicated in the pathogenesis of Parkinson's disease (PD). The glycine to serine mutation (G2019S) in leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause for PD and has been shown to impair mitochondrial function and morphology in multiple model systems. We analyzed mitochondrial function in LRRK2 G2019S induced pluripotent stem cell (iPSC)-derived neurons to determine whether the G2019S mutation elicits similar mitochondrial deficits among central and peripheral nervous system neuron subtypes...
October 31, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29120562/be-vigilant-for-dementia-in-parkinson%C3%A2-s-disease
#3
Flavia Niccolini, Konstantinos Diamantopoulos, Stelios Kiosses, Marios Politis
It is estimated that up to 80% of patients with Parkinson's disease will eventually develop cognitive impairment over the course of their illness. Even at the time of diagnosis, cognitive impairment has been reported in 20-25% of patients. Commonly affected cognitive domains are executive function, visuospatial ability and attention control. In addition, patients with Parkinson's disease dementia may present with deficits in language function and verbal memory. Psychosis may occur in approximately 40% of patients with Parkinson's disease, and is associated with an increased risk of developing cognitive impairment...
May 2017: Practitioner
https://www.readbyqxmd.com/read/29119863/understanding-uncertainty-in-young-onset-parkinson-disease
#4
Michael Ravenek, Debbie L Rudman, Mary E Jenkins, Sandi Spaulding
Objectives Individuals living with young-onset Parkinson's disease compose a rare subtype of a disease typically associated with older age. Situated within a large grounded theory study exploring information behavior, this paper describes the core category of the theory, i.e. uncertainty. Methods Data were collected with 39 individuals living with young-onset Parkinson's disease who took part in in-depth interviews, focus groups and/or an online discussion board. Fourteen autobiographies written by individuals living with young-onset Parkinson's disease were also used as data sources...
December 2017: Chronic Illness
https://www.readbyqxmd.com/read/29119593/prediction-of-cognitive-worsening-in-de-novo-parkinson-s-disease-clinical-use-of-biomarkers
#5
Dario Arnaldi, Fabrizio De Carli, Francesco Famà, Andrea Brugnolo, Nicola Girtler, Agnese Picco, Matteo Pardini, Jennifer Accardo, Luca Proietti, Federico Massa, Matteo Bauckneht, Silvia Morbelli, Gianmario Sambuceti, Flavio Nobili
BACKGROUND: Cognitive impairment is a frequent and disabling feature of Parkinson's disease. Identifying the factors able to predict cognitive worsening since the early stage may improve disease management. The objective of this study was to define the best predictors of future cognitive worsening in a group of patients with newly diagnosed PD and to propose cutoff values potentially useful at the individual level. METHODS: Fifty-four consecutive drug-naive patients with de novo PD were prospectively evaluated by clinical and neuropsychological assessment, resting EEG, and (123) I-FP-CIT-SPECT and clinically classified into mainly motor, diffuse/malignant, and intermediate PD subtypes; they were then followed up for an average of 5 years...
November 9, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29104810/management-of-psychosis-in-parkinson-s-disease-emphasizing-clinical-subtypes-and-pathophysiological-mechanisms-of-the-condition
#6
REVIEW
Raquel N Taddei, Seyda Cankaya, Sandeep Dhaliwal, K Ray Chaudhuri
Investigation into neuropsychiatric symptoms in Parkinson's disease (PD) is sparse and current drug development is mainly focused on the motor aspect of PD. The tight association of psychosis with an impaired quality of life in PD, together with an important underreporting of this comorbid condition, contributes to its actual insufficient assessment and management. Furthermore, the withdrawal from access to readily available treatment interventions is unacceptable and has an impact on PD prognosis. Despite its impact, to date no standardized guidelines to the adequate management of PD psychosis are available and they are therefore highly needed...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/29102236/rem-sleep-behavior-disorder-portends-poor-prognosis-in-parkinson-s-disease-a-systematic-review
#7
REVIEW
Yoon Kim, Young Eun Kim, Eun Ok Park, Chae Won Shin, Han-Joon Kim, Beomseok Jeon
REM sleep behavior disorder (RBD) is a parasomnia wherein a loss of REM sleep atonia manifests as dream-enactment, often violent. Aside from its significance as a predictor of PD, RBD in PD may imply more than merely screaming at night and experiencing sleep fragmentation. To probe its significance as a prognostic factor in PD, we performed a systematic literature review. Analysis of prospective studies reveals baseline RBD confers a higher risk of developing dementia and hallucinations. In cross-sectional studies, RBD is associated with the non-tremor predominant motor phenotype and autonomic dysfunction...
October 25, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29082105/a-case-of-beta-propeller-protein-associated-neurodegeneration-due-to-a-heterozygous-deletion-of-wdr45
#8
Andreas Hermann, Hagen H Kitzler, Tobias Pollack, Saskia Biskup, Stefanie Krüger, Claudia Funke, Caterina Terrile, Tobias B Haack
BACKGROUND: Static encephalopathy of childhood with neurodegeneration in adulthood is a phenotypically distinctive, X-linked dominant subtype of neurodegeneration with brain iron accumulation (NBIA). WDR45 mutations were recently identified as causal. WDR45 encodes a beta-propeller scaffold protein with a putative role in autophagy, and the disease has been renamed beta-propeller protein-associated neurodegeneration (BPAN). CASE REPORT: Here we describe a female patient suffering from a classical BPAN phenotype due to a novel heterozygous deletion of WDR45...
2017: Tremor and Other Hyperkinetic Movements
https://www.readbyqxmd.com/read/29063640/amyotrophic-lateral-sclerosis-and-parkinsonism-dementia-complex-of-the-hohara-focus-of-the-kii-peninsula-a-multiple-proteinopathy
#9
REVIEW
Maya Mimuro, Mari Yoshida, Shigeki Kuzuhara, Yasumasa Kokubo
The high incidence of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) has been previously known in the Kii Peninsula of Japan and in Guam. Recently, the accumulation of various proteins, such as tau, trans-activation response DNA binding protein 43 kDa (TDP-43), and alpha-synuclein (αSyn), was reported in the brains of patients with ALS/PDC in Guam. To confirm whether similar findings are present in Kii ALS/PDC, we neuropathologically examined the brains and spinal cords of 18 patients with ALS/PDC (clinical diagnoses: eight ALS and 10 PDC) in Hohara Village, which is the eastern focus of Kii ALS...
October 23, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29060541/detection-of-gait-initiation-failure-in-parkinson-s-disease-based-on-wavelet-transform-and-support-vector-machine
#10
Quynh Tran Ly, A M Ardi Handojoseno, Moran Gilat, Rifai Chai, Kaylena A Ehgoetz Martens, Matthew Georgiades, Ganesh R Naik, Yvonne Tran, Simon J G Lewis, Hung T Nguyen
Gait initiation Failure (GIF) is the situation in which patients with Parkinson's disease (PD) feel as if their feet get "stuck" to the floor when initiating their first steps. GIF is a subtype of Freezing of Gait (FOG) and often leads to falls and related injuries. Understanding of neurobiological mechanisms underlying GIF has been limited by difficulties in eliciting and objectively characterizing such gait phenomena in the clinical setting. Studies investigating the effects of GIF on brain activity using EEG offer the potential to study such behavior...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29053860/clinicopathological-correlations-in-behavioural-variant-frontotemporal-dementia
#11
David C Perry, Jesse A Brown, Katherine L Possin, Samir Datta, Andrew Trujillo, Anneliese Radke, Anna Karydas, John Kornak, Ana C Sias, Gil D Rabinovici, Maria Luisa Gorno-Tempini, Adam L Boxer, Mary De May, Katherine P Rankin, Virginia E Sturm, Suzee E Lee, Brandy R Matthews, Aimee W Kao, Keith A Vossel, Maria Carmela Tartaglia, Zachary A Miller, Sang Won Seo, Manu Sidhu, Stephanie E Gaus, Alissa L Nana, Jose Norberto S Vargas, Ji-Hye L Hwang, Rik Ossenkoppele, Alainna B Brown, Eric J Huang, Giovanni Coppola, Howard J Rosen, Daniel Geschwind, John Q Trojanowski, Lea T Grinberg, Joel H Kramer, Bruce L Miller, William W Seeley
Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical for the success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations in a large bvFTD cohort. Among 438 patients in whom bvFTD was either the top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 with a primary pathological diagnosis of frontotemporal lobar degeneration (FTLD), 15 with Alzheimer's disease, and four with amyotrophic lateral sclerosis who lacked neurodegenerative disease-related pathology outside of the motor system...
October 6, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29050386/brain-monoamine-oxidase-b-and-a-in-human-parkinsonian-dopamine-deficiency-disorders
#12
Junchao Tong, Gausiha Rathitharan, Jeffrey H Meyer, Yoshiaki Furukawa, Lee-Cyn Ang, Isabelle Boileau, Mark Guttman, Oleh Hornykiewicz, Stephen J Kish
See Jellinger (doi:10.1093/awx190) for a scientific commentary on this article. The enzyme monoamine oxidases (B and A subtypes, encoded by MAOB and MAOA, respectively) are drug targets in the treatment of Parkinson's disease. Inhibitors of MAOB are used clinically in Parkinson's disease for symptomatic purposes whereas the potential disease-modifying effect of monoamine oxidase inhibitors is debated. As astroglial cells express high levels of MAOB, the enzyme has been proposed as a brain imaging marker of astrogliosis, a cellular process possibly involved in Parkinson's disease pathogenesis as elevation of MAOB in astrocytes might be harmful...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29036826/what-can-quantitative-gait-analysis-tell-us-about-dementia-and-its-subtypes-a-structured-review
#13
Ríona Mc Ardle, Rosie Morris, Joanna Wilson, Brook Galna, Alan J Thomas, Lynn Rochester
Distinguishing dementia subtypes can be difficult due to similarities in clinical presentation. There is increasing interest in discrete gait characteristics as markers to aid diagnostic algorithms in dementia. This structured review explores the differences in quantitative gait characteristics between dementia and healthy controls, and between four dementia subtypes under single-task conditions: Alzheimer's disease (AD), dementia with Lewy bodies and Parkinson's disease dementia, and vascular dementia. Twenty-six papers out of an initial 5,211 were reviewed and interpreted using a validated model of gait...
October 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29033972/clinical-spectrum-risk-factors-and-behavioral-abnormalities-among-dementia-subtypes-in-a-north-indian-population-a-hospital-based-study
#14
Suman Kushwaha, Puneet Talwar, Aldrin Anthony, Meena Gupta, Kiran Bala, Rachna Agarwal, Vibha Sharma, Ritushree Kukreti
BACKGROUND: As variability in the clinical profile of dementia subtypes had been reported with regional differences across the world, we conducted a retrospective hospital-based study in a North Indian population. METHODS: We retrieved patient records from 2007 to 2014 for details of clinical evaluation, diagnosis, neuroimaging, biochemical investigations, and follow-up of 1,876 patients with dementia (PwD), and the data were analyzed using descriptive statistics...
May 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/28993732/purinergic-signalling-therapeutic-developments
#15
REVIEW
Geoffrey Burnstock
Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990's when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28993094/characterization-of-diplopia-in-non-demented-patients-with-parkinson-s-disease
#16
Katharina A Schindlbeck, Shideh Schönfeld, Wanda Naumann, David J Friedrich, André Maier, Charlotte Rewitzer, Fabian Klostermann, Frank Marzinzik
INTRODUCTION: Although diplopia is considered a frequent symptom of Parkinson's disease (PD), little is known about its clinical manifestation, associated mechanisms and treatment. Here we characterized binocular diplopia in non-demented PD patients in an interdisciplinary setting. METHODS: PD patients were prospectively screened for diplopia, visual hallucinations, problems with spatial perception, contrast sensitivity, presence of blurred vision, and history of ophthalmological comorbidities via interview...
September 29, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28979204/hyposmia-is-associated-with-rbd-for-pd-patients-with-variants-of-snca
#17
Yuanyuan Li, Wenyan Kang, Linyuan Zhang, Liche Zhou, Mengyue Niu, Jun Liu
Objective: Hyposmia may occur simultaneously with REM sleep behavior disorder (RBD) as a specific phenotype in Parkinson's Diseases (PD), of which the disease progression is fast. In the study, we tried to identify whether the genotypic characteristics could participate in the co-occurrence of hyposmia and RBD in PD patients. Methods: 152 PD patients were recruited from the Department of Neurology, Ruijin Hospital affiliated to Shanghai JiaoTong University School of Medicine from 2011 to 2016, with comprehensive clinical assessment performing...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28979203/parkinson-s-disease-subtypes-identified-from-cluster-analysis-of-motor-and-non-motor-symptoms
#18
Jesse Mu, Kallol R Chaudhuri, Concha Bielza, Jesus de Pedro-Cuesta, Pedro Larrañaga, Pablo Martinez-Martin
Parkinson's disease is now considered a complex, multi-peptide, central, and peripheral nervous system disorder with considerable clinical heterogeneity. Non-motor symptoms play a key role in the trajectory of Parkinson's disease, from prodromal premotor to end stages. To understand the clinical heterogeneity of Parkinson's disease, this study used cluster analysis to search for subtypes from a large, multi-center, international, and well-characterized cohort of Parkinson's disease patients across all motor stages, using a combination of cardinal motor features (bradykinesia, rigidity, tremor, axial signs) and, for the first time, specific validated rater-based non-motor symptom scales...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28970788/altered-functional-connectivity-density-in-subtypes-of-parkinson-s-disease
#19
Xiaofei Hu, Yuchao Jiang, Xiaomei Jiang, Jiuquan Zhang, Minglong Liang, Jing Li, Yanling Zhang, Dezhong Yao, Cheng Luo, Jian Wang
Parkinson's disease (PD) can be classified into tremor-dominant and akinetic-rigid subtypes, each of which exhibits a unique clinical course and prognosis. The neural basis for these disparate manifestations is not well-understood, however. This study comprehensively investigated the altered functional connectivity patterns of these two subtypes. Twenty-five tremor-dominant patients, 25 akinetic-rigid patients and 26 normal control subjects participated in this study. Resting-state functional MRI data were analyzed using functional connectivity density (FCD) and seed-based functional connectivity approaches...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28965701/environmental-exposure-to-manganese-in-air-tremor-motor-and-cognitive-symptom-profiles
#20
E S Kornblith, S L Casey, D T Lobdell, M A Colledge, R M Bowler
BACKGROUND: Excessive exposure to manganese (Mn) may cause parkinsonian-like motor and tremor symptoms and adverse cognitive effects, including problems with executive functioning (EF), resembling those found in later-stage Parkinson's disease (PD). Studies seeking to differentiate PD patients into subgroups with associated cognitive and functional outcomes using motor and tremor symptoms identified tremor-dominant (TD) and non-tremor dominant (NTD) subtypes. It is unclear whether differing patterns of pathophysiology and symptoms exist in Mn neurotoxicity, as they do in PD...
September 28, 2017: Neurotoxicology
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