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https://www.readbyqxmd.com/read/27911344/patient-perspectives-on-deep-brain-stimulation-clinical-research-in-early-stage-parkinson-s-disease
#1
Lauren Heusinkveld, Mallory Hacker, Maxim Turchan, Madelyn Bollig, Christina Tamargo, William Fisher, Lauren McLaughlin, Adria Martig, David Charles
The FDA approved a multicenter, double-blind, Phase III, pivotal trial testing deep brain stimulation in 280 people with very early stage Parkinson's disease (PD; IDE#G050016). In partnership with The Michael J. Fox Foundation for Parkinson's Research, we conducted a survey to investigate motivating factors, barriers, and gender differences for participation in a trial testing DBS in early PD. The majority of survey respondents (72%) indicated they would consider learning more about participating. Men and women with early PD are likely to consider enrolling in trials of invasive therapies that may slow symptom progression and help future patients...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27911343/pink1-parkin-and-mitochondrial-quality-control-what-can-we-learn-about-parkinson-s-disease-pathobiology
#2
Dominika Truban, Xu Hou, Thomas R Caulfield, Fabienne C Fiesel, Wolfdieter Springer
The first clinical description of Parkinson's disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process known as mitophagy...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27911342/impulsive-and-compulsive-behaviors-in%C3%A2-parkinson-disease-the-norwegian-parkwest-study
#3
Aleksander H Erga, Guido Alves, Jan Petter Larsen, Ole Bj Rn Tysnes, Kenn Freddy Pedersen
BACKGROUND: Impulsive and compulsive behaviors (ICBs) are frequent in Parkinson's disease (PD), but data from population-based cohorts is lacking. OBJECTIVES: To determine the frequency and associated demographic, clinical, neuropsychiatric and cognitive features of ICBs in a population-based PD cohort. METHODS: This cross-sectional study included 125 patients with PD and 159 age- and gender-matched normal controls recruited from the Norwegian ParkWest study...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27911341/longer-duration-of-mao-b-inhibitor-exposure-is-associated-with-less-clinical-decline-in-parkinson-s-disease-an%C3%A2-analysis%C3%A2-of%C3%A2-net-pd-ls1
#4
Robert A Hauser, Ruosha Li, Adriana Pérez, Xuehan Ren, Dan Weintraub, Jordan Elm, John L Goudreau, John C Morgan, John Y Fang, Michael J Aminoff, Chadwick W Christine, Rohit Dhall, Chizoba C Umeh, James T Boyd, Natividad Stover, Maureen Leehey, Richard M Zweig, Anthony P Nicholas, Ivan Bodis-Wollner, Allison Willis, Karl Kieburtz, Barbara C Tilley
BACKGROUND: Monoamine oxidase type B (MAO-B) inhibitors exhibit neuroprotective effects in preclinical models of PD but clinical trials have failed to convincingly demonstrate disease modifying benefits in PD patients. OBJECTIVE: To perform a secondary analysis of NET-PD LS1 to determine if longer duration of MAO-B inhibitor exposure was associated with less clinical decline. METHODS: The primary outcome measure was the Global Outcome (GO), comprised of 5 measures: change from baseline in the Schwab and England (ADL) scale, the 39-item Parkinson's Disease Questionnaire (PDQ-39), the UPDRS Ambulatory Capacity Scale, the Symbol Digit Modalities Test, and the most recent Modified Rankin Scale...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27911340/dementia-predictors-in-parkinson-disease-a-validation-study
#5
Julius Bm Anang, Takashi Nomura, Silvia Rios Romenets, Kenji Nakashima, Jean-Francois Gagnon, Ronald B Postuma
In a prospective study, we recently discovered 8 clinical predictors of dementia in Parkinson's disease. Here, we validate these dementia predictors using two additional prospective cohorts (n = 134). After a 3.6-year follow-up, 35/134 developed dementia (7.2% per year). When confirming individual variables, 5/8 were significantly associated with dementia in the validation cohort. These included age, male sex, baseline RBD, orthostatic hypotension, and MCI. Bilateral onset, hallucinations and falls/freezing did not significantly predict dementia; however, point estimates of OR were all >1...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27911316/risk-factors-for-mild-cognitive-impairment-in-german-primary-care-practices
#6
Louis Jacob, Jens Bohlken, Karel Kostev
BACKGROUND: Mild cognitive impairment (MCI) is a common mental disorder affecting around 16% of elderly people without dementia. MCI is considered an intermediate state between normal cognition and dementia. OBJECTIVE: To analyze risk factors for the development of MCI in German primary care practices. METHODS: In total, 3,604 MCI patients and 3,604 controls without MCI were included between January 2010 and December 2015. Several disorders potentially associated with MCI were determined...
December 1, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911312/increased-transforming-growth-factor-%C3%AE-2-in-the-neocortex-of-alzheimer-s-disease-and-dementia-with-lewy-bodies-is%C3%A2-correlated-with-disease-severity-and%C3%A2-soluble-a%C3%AE-42-load
#7
Joyce R Chong, Yuek Ling Chai, Jasinda H Lee, David Howlett, Johannes Attems, Clive G Ballard, Dag Aarsland, Paul T Francis, Christopher P Chen, Mitchell K P Lai
BACKGROUND: Of the three transforming growth factor (TGF)-β isoforms known, TGFβ1 deficits have been widely reported in Alzheimer's disease (AD) and studied as a potential therapeutic target. In contrast, the status of TGFβ2, which has been shown to mediate amyloid-β (Aβ)-mediated neuronal death, are unclear both in AD and in Lewy body dementias (LBD) with differential neuritic plaque and neurofibrillary tangle burden. OBJECTIVE: To measure neocortical TGFβ2 levels and their correlations with neuropathological and clinical markers of disease severity in a well-characterized cohort of AD as well as two clinical subtypes of LBD, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), known to manifest relatively high and low Aβ plaque burden, respectively...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911071/severe-brain-injury-in-massachusetts-assessing-the-continuum-of-care
#8
Laura Lorenz, Gabrielle Katz
Acquired brain injury (ABI) is a major public health problem in Massachusetts (Hackman et al, 2014) and includes traumatic brain injury (TBI), stroke, ABI-related infectious diseases, metabolic disorders affecting the central nervous system (brain and spinal cord), and brain tumor. Advances in emergency medical care and neurosurgery mean that more people are surviving severe traumatic brain injury (Trexler et al, 2014). Yet many patients with severe TBI in particular, are not receiving inpatient services after initial treatment (Hackman et al, 2014; CDC, 2014) or later that are known to be effective (Malec & Kean, 2015; Lewis & Horn, 2015; BI Commission, 2011; Kolakowsky-Hayner et al, 2000; Interviews)...
December 10, 2015: Issue Brief
https://www.readbyqxmd.com/read/27911022/membrane-defects-and-genetic-redundancy-are-we-at-a-turning-point-for-dyt1-dystonia
#9
REVIEW
Ana Cascalho, Julie Jacquemyn, Rose E Goodchild
Heterozygosity for a 3-base pair deletion (ΔGAG) in TOR1A/torsinA is one of the most common causes of hereditary dystonia. In this review, we highlight current understanding of how this mutation causes disease from research spanning structural biochemistry, cell science, neurobiology, and several model organisms. We now know that homozygosity for ΔGAG has the same effects as Tor1a(KO) , implicating a partial loss of function mechanism in the ΔGAG/+ disease state. In addition, torsinA loss specifically affects neurons in mice, even though the gene is broadly expressed, apparently because of differential expression of homologous torsinB...
December 2, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27911020/changes-in-resting-state-connectivity-in-musicians-with-embouchure-dystonia
#10
Bernhard Haslinger, Jonas Noé, Eckart Altenmüller, Valentin Riedl, Claus Zimmer, Tobias Mantel, Christian Dresel
OBJECTIVE: Embouchure dystonia is a highly disabling task-specific dystonia in professional brass musicians leading to spasms of perioral muscles while playing the instrument. As they are asymptomatic at rest, resting-state functional magnetic resonance imaging in these patients can reveal changes in functional connectivity within and between brain networks independent from dystonic symptoms. METHODS: We therefore compared embouchure dystonia patients to healthy musicians with resting-state functional magnetic resonance imaging in combination with independent component analyses...
December 2, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27911008/comparison-of-neuropathology-in-parkinson-s-disease-subjects-with-and-without-deep-brain-stimulation
#11
Gian D Pal, Bichun Ouyang, Geidy Serrano, Holly A Shill, Christopher Goetz, Glenn Stebbins, Leo Verhagen Metman, Erika Driver-Dunckley, Shyamal H Mehta, John N Caviness, Marwan N Sabbagh, Charles H Adler, Thomas G Beach
BACKGROUND: The aim of this postmortem study was to compare, in Parkinson's disease subjects with and without bilateral subthalamic nucleus deep brain stimulation (STN-DBS), the loss of pigmented neurons within the substantia nigra and pathological alpha-synuclein density within the SN and other brain regions. METHODS: PD subjects were identified from the Arizona Study of Aging and Neurodegenerative Disorders database (STN-DBS = 11, non-DBS = 156). Pigmented neuron loss scores within the substantia nigra as well as alpha-synuclein density scores within the substantia nigra and 9 other brain regions were compared, the latter individually and in summary as the Lewy body brain load score...
December 2, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27911006/lrrk2-levels-and-phosphorylation-in-parkinson-s-disease-brain-and-cases-with-restricted-lewy-bodies
#12
Nicolas Dzamko, Amanda M Gysbers, Rina Bandopadhyay, Marc F Bolliger, Akiko Uchino, Ye Zhao, Masaki Takao, Sandrine Wauters, Wilma D J van de Berg, Junko Takahashi-Fujigasaki, R Jeremy Nichols, Janice L Holton, Shigeo Murayama, Glenda M Halliday
BACKGROUND: Leucine rich repeat kinase 2 (LRRK2) is a promising target for the treatment of Parkinson's disease; however, little is known about the expression of LRRK2 in human brain and if/how LRRK2 protein levels are altered in Parkinson's disease. OBJECTIVES: We measured the protein levels of LRRK2 as well as its phosphorylation on serines 910, 935, and 973 in the postmortem brain tissue of Parkinson's disease patients and aged controls with and without Lewy bodies...
December 2, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27911002/what-is-quality-of-life-and-how-do-we-measure-it-relevance-to-parkinson-s-disease-and-movement-disorders
#13
REVIEW
Pablo Martinez-Martin
Health-related quality of life is a patient-reported outcome that complements clinical evaluation and provides information about disease activity and effects of the treatment. The objective of this review is to present the conceptual framework, the measures, and some of their most relevant applications in the field of Parkinson's disease and movement disorders. Health-related quality of life is a subjective, individual, and multidimensional construct, and its main dimensions are physical, mental, and social, besides global perceptions of health and personal domains...
December 2, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27909646/the-neural-mechanisms-of-meditative-practices-novel-approaches-for-healthy-aging
#14
REVIEW
Bianca P Acevedo, Sarah Pospos, Helen Lavretsky
OBJECTIVES: Meditation has been shown to have physical, cognitive, and psychological health benefits that can be used to promote healthy aging. However, the common and specific mechanisms of response remain elusive due to the diverse nature of mind-body practices. METHODS: In this review, we aim to compare the neural circuits implicated in focused-attention meditative practices that focus on present-moment awareness to those involved in active-type meditative practices (e...
2016: Current Behavioral Neuroscience Reports
https://www.readbyqxmd.com/read/27909246/retromer-wash-dependent-sorting-of-nutrient-transporters-requires-a-multivalent-interaction-network-with-ankrd50
#15
Arunas Kvainickas, Ana Jimenez Orgaz, Heike Nägele, Britta Diedrich, Kate J Heesom, Jörn Dengjel, Peter J Cullen, Florian Steinberg
Retromer and the associated actin polymerizing WASH-complex are essential for the endocytic recycling of a wide range of integral membrane proteins. A hereditary Parkinson's disease causing point mutation (D620N) in the retromer subunit VPS35 perturbs retromer's association with the WASH-complex and also with the uncharacterized protein Ankyrin Repeat Domain Containing Protein 50 (ANKRD50). Here, we firmly establish ANKRD50 as a novel and essential component of the SNX27-retromer-WASH supercomplex. Depletion of ANKRD50 in HeLa or U2OS cells phenocopied the loss of endosome to cell surface recycling of multiple transmembrane proteins seen upon suppression of SNX27, retromer or WASH-complex components...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27908790/mpp-inhibits-mglur1-5-mediated-long-term-depression-in-mouse-hippocampus-by-calpain-activation
#16
Junyao Li, Hui Chen, Shengbing Wu, Yuefa Cheng, Qinglin Li, Jing Wang, Guoqi Zhu
Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of neurotoxin, 1-methyl-4-phenylpyridinium (MPP(+)), on metabotropic glutamate receptor 1/5 agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced hippocampal synaptic plasticity, and MPP(+) incubation blocked DHPG-induced hippocampal long-term depression (LTD) in Schaffer collateral-CA1 synapses...
November 28, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27908782/adaptive-responses-of-neuronal-mitochondria-to-bioenergetic-challenges-roles-in-neuroplasticity-and-disease-resistance
#17
REVIEW
Sophia M Raefsky, Mark P Mattson
An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27908423/copper-brain-protein-protection-against-free-radical-induced-neuronal-death-survival-ratio-in-sh-sy5y-neuroblastoma-cell-cultures
#18
Roger Deloncle, Bernard Fauconneau, Olivier Guillard, José Delaval, Gérard Lesage, Alain Pineau
In Creutzfeldt Jakob, Alzheimer and Parkinson diseases, copper metalloproteins such as prion, amyloid protein precursor and α-synuclein are able to protect against free radicals by reduction from cupric Cu(+2) to cupreous Cu(+). In these pathologies, a regional copper (Cu) brain decrease correlated with an iron, zinc or manganese (Mn) increase has previously been observed, leading to local neuronal death and abnormal deposition of these metalloproteins in β-sheet structures. In this study we demonstrate the protective effect of Cu metalloproteins against deleterious free-radical effects...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27908171/automated-detection-of-white-matter-hyperintensities-of-all-sizes-in-cerebral-small-vessel-disease
#19
Mohsen Ghafoorian, Nico Karssemeijer, Inge W M van Uden, Frank-Erik de Leeuw, Tom Heskes, Elena Marchiori, Bram Platel
PURPOSE: White matter hyperintensities (WMH) are seen on FLAIR-MRI in several neurological disorders, including multiple sclerosis, dementia, Parkinsonism, stroke and cerebral small vessel disease (SVD). WMHs are often used as biomarkers for prognosis or disease progression in these diseases, and additionally longitudinal quantification of WMHs is used to evaluate therapeutic strategies. Human readers show considerable disagreement and inconsistency on detection of small lesions. A multitude of automated detection algorithms for WMHs exists, but since most of the current automated approaches are tuned to optimize segmentation performance according to Jaccard or Dice scores, smaller WMHs often go undetected in these approaches...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/27907896/harnessing-human-adar2-for-rna-repair-recoding-a-pink1-mutation-rescues-mitophagy
#20
Jacqueline Wettengel, Philipp Reautschnig, Sven Geisler, Philipp J Kahle, Thorsten Stafforst
Site-directed A-to-I RNA editing is a technology for re-programming genetic information at the RNA-level. We describe here the first design of genetically encodable guideRNAs that enable the re-addressing of human ADAR2 toward specific sites in user-defined mRNA targets. Up to 65% editing yield has been achieved in cell culture for the recoding of a premature Stop codon (UAG) into tryptophan (UIG). In the targeted gene, editing was very specific. We applied the technology to recode a recessive loss-of-function mutation in PINK1 (W437X) in HeLa cells and showed functional rescue of PINK1/Parkin-mediated mitophagy, which is linked to the etiology of Parkinson's disease...
October 7, 2016: Nucleic Acids Research
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