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https://www.readbyqxmd.com/read/28641977/a-novel-fluorescent-probe-reveals-starvation-controls-the-commitment-of-amyloid-precursor-protein-to-the-lysosome
#1
Leanne K Hein, Pirjo M Apaja, Kathryn Hattersley, Randall H Grose, Jianling Xie, Christopher G Proud, Timothy J Sargeant
Alzheimer's disease is the most important cause of dementia but there is no therapy that has been demonstrated to stop or slow disease progression. Amyloid precursor protein (APP) is the source of amyloid-β (Aβ), which aggregates in Alzheimer's disease to form toxic oligomeric species. The endo-lysosomal system can clear APP and Aβ from the cell if these molecular species are trafficked through to the lysosome. Currently, there are no easy methods available for the analysis of lysosomal APP trafficking. We therefore generated a fusion protein (tandem-fluorescent, or tf-APP) that allows detection of changes in APP trafficking using accessible techniques such as flow cytometry...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28639878/exploring-the-phenotype-in-mild-cognitive-impairment-to-aid-the-prediction-of-those-at-risk-of-transitioning-to-parkinson-disease-and-dementia-with-lewy-bodies
#2
Jennifer Y Y Szeto, Glenda M Halliday, Sharon L Naismith, Simon J G Lewis
To date, only limited research has concurrently investigated the presence of rapid eye movement sleep behavior disorder (RBD) and other features associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB) in people presenting with mild cognitive impairment (MCI). As a first step towards a longitudinal research project, the present study explored the relationships between MCI, RBD, and depression in 108 older adults who presented with subjective memory complaints but were not known to have a neurodegenerative condition...
July 2017: Journal of Geriatric Psychiatry and Neurology
https://www.readbyqxmd.com/read/28639724/longitudinal-changes-in-global-and-domain-specific-cognitive-function-in-the-very-old-findings-from-the-newcastle-85-study
#3
Blossom C M Stephan, Graciela Muniz-Terrera, Antoneta Granic, Joanna Collerton, Karen Davies, Brian K Saxby, Keith A Wesnes, Thomas B L Kirkwood, Carol Jagger
OBJECTIVE: Ageing is associated with changes in cognition in some, but not all domains. In young-old adults, defined as persons aged 65-84 years, baseline cognitive function has been shown to impact on cognitive trajectories. Whether similar patterns occur in the very-old, defined as persons aged 85 years and over, is not known. METHODS: Longitudinal changes (5 years' follow-up) in global and domain specific cognitive function including memory, attention and speed were investigated in participants from the Newcastle 85+ Study (n = 845)...
June 22, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28632037/construct-and-concurrent-validity-of-the-cambridge-neuropsychological-automated-tests-in-portuguese-older-adults-without-neuropsychiatric-diagnoses-and-with-alzheimer-s-disease-dementia
#4
Marta Matos Gonçalves, Maria Salomé Pinho, Mário R Simões
We aimed to analyze the construct and concurrent validity of the Rapid Visual Information Processing (RVP), Paired Associates Learning (PAL), Reaction Time (RTI), and Spatial Working Memory (SWM) tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB®). Inclusion criteria were checked in a first session. The CANTAB and additional pencil-and-paper tests were administered within 1 week. The participants (aged 69-96 years) were 137 Portuguese adults without neuropsychiatric diagnoses and 37 adults with mild-to-moderate Alzheimer's disease dementia...
February 28, 2017: Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition
https://www.readbyqxmd.com/read/28631971/rapidly-progressive-dementia-an-unusual-cause
#5
Aastha Takkar, Veenu Singla, Manish Modi, Vivek Gupta, Manoj K Goyal, Vivek Lal
Brain metastases are known to be present with a history of increased intra-cranial pressure headache, seizures or altered sensorium. Corresponding to the clinical brain metastases are the most feared complication of a systemic cancer. Classically, brain metastases are associated with significant morbidity and are known to present with a history of increased intracranial pressure headache, seizures or altered sensorium. Neuroimaging is usually suggestive of massive peri-lesional edema and mass effect surrounding the space occupying lesions...
January 1, 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28627378/practical-risk-score-for-5-10-and-20-year-prediction-of-dementia-in%C3%A2-elderly-persons-framingham-heart-study
#6
Jinlei Li, Matthew Ogrodnik, Sherral Devine, Sanford Auerbach, Philip A Wolf, Rhoda Au
INTRODUCTION: With a rapidly aging population, general practitioners are confronting the challenge of how to determine those who are at greatest risk for dementia and potentially need more specialized follow-up to mitigate symptoms early in its course. We created a practical dementia risk score and provided individualized estimates of future dementia risk. METHODS: Using the Framingham Heart Study data, we built our prediction model using Cox proportional hazard models and developed a point system for the risk score and risk estimates...
June 13, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28626409/hiv-associated-cerebellar-dysfunction-and-improvement-with-aminopyridine-therapy-a-case-report
#7
Carolin Hoyer, Angelika Alonso, Beate Schlotter-Weigel, Michael Platten, Marc Fatar
Apart from infectious causes and cerebellar dysfunction associated with acquired immune deficiency syndrome dementia or HIV-associated neurocognitive disorder, cerebellar dysfunction in HIV-positive individuals has been ascribed to granule cell neuronopathy as well as primary cerebellar atrophy without identifiable etiology. We report the case of a patient with progressive cerebellar dysfunction as the primary manifestation of HIV infection. No symptom improvement was seen under combination antiretroviral therapy, which had been established upon diagnosis, but the patient improved rapidly under 4-aminopyridine treatment, which was recommended 1 year later...
May 2017: Case Reports in Neurology
https://www.readbyqxmd.com/read/28620783/advanced-neuroimaging-of-cerebral-small-vessel-disease
#8
REVIEW
Gordon W Blair, Maria Valdez Hernandez, Michael J Thrippleton, Fergus N Doubal, Joanna M Wardlaw
Cerebral small vessel disease (SVD) is characterised by damage to deep grey and white matter structures of the brain and is responsible for a diverse range of clinical problems that include stroke and dementia. In this review, we describe advances in neuroimaging published since January 2015, mainly with magnetic resonance imaging (MRI), that, in general, are improving quantification, observation and investigation of SVD focussing on three areas: quantifying the total SVD burden, imaging brain microstructural integrity and imaging vascular malfunction...
July 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28620158/clinical-features-and-sleep-analysis-of-chinese-patients-with-fatal-familial-insomnia
#9
Liyong Wu, Hui Lu, Xianling Wang, Jia Liu, Chaoyang Huang, Jing Ye, Cuijiang Li, Jun Lu, Yuping Wang, Jianping Jia, Shuqin Zhan
This study aimed to examine clinical features, sleep, abnormal sleep-wake transition and non-sleep disturbances as well as lab tests in Chinese fatal familial insomnia (FFI) subjects. Patients with confirmed clinical and laboratory diagnosis of FFI have been retrospectively reviewed. The clinical features and the results of the complementary tests, including polysomnography (PSG), brain imaging and genetic analysis, were used. Two male and three female patients were recruited in this study. Three of the five patients had more comprehensive family medical records...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28602509/neurochip-an-updated-version-of-the-neurox-genotyping-platform-to-rapidly-screen-for-variants-associated-with-neurological-diseases
#10
Cornelis Blauwendraat, Faraz Faghri, Lasse Pihlstrom, Joshua T Geiger, Alexis Elbaz, Suzanne Lesage, Jean-Christophe Corvol, Patrick May, Aude Nicolas, Yevgeniya Abramzon, Natalie A Murphy, J Raphael Gibbs, Mina Ryten, Raffaele Ferrari, Jose Bras, Rita Guerreiro, Julie Williams, Rebecca Sims, Steven Lubbe, Dena G Hernandez, Kin Y Mok, Laurie Robak, Roy H Campbell, Ekaterina Rogaeva, Bryan J Traynor, Ruth Chia, Sun Ju Chung, John A Hardy, Alexis Brice, Nicholas W Wood, Henry Houlden, Joshua M Shulman, Huw R Morris, Thomas Gasser, Rejko Krüger, Peter Heutink, Manu Sharma, Javier Simón-Sánchez, Mike A Nalls, Andrew B Singleton, Sonja W Scholz
Genetics has proven to be a powerful approach in neurodegenerative diseases research, resulting in the identification of numerous causal and risk variants. Previously, we introduced the NeuroX Illumina genotyping array, a fast and efficient genotyping platform designed for the investigation of genetic variation in neurodegenerative diseases. Here, we present its updated version, named NeuroChip. The NeuroChip is a low-cost, custom-designed array containing a tagging variant backbone of about 306,670 variants complemented with a manually curated custom content comprised of 179,467 variants implicated in diverse neurological diseases, including Alzheimer's disease, Parkinson's disease, Lewy body dementia, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy...
May 17, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28600159/building-research-in-diet-and-cognition-the-bridge-randomized-controlled-trial
#11
Lisa Tussing-Humphreys, Melissa Lamar, James A Blumenthal, Michael Babyak, Giamila Fantuzzi, Lara Blumstein, Linda Schiffer, Marian L Fitzgibbon
Obesity has been linked to cognitive impairment, cognitive decline and dementia. Given that 38.5% of U.S. adults 60years and older are obese and these numbers are rapidly increasing, strategies to decouple obesity from cognitive decline are needed. Innovative lifestyle strategies that may postpone the onset of subclinical symptoms or even arrest the transition to overt dementia in at-risk individuals are critically needed. Poor diet is central to the development of obesity and diet may affect cognition. Adherence to a Mediterranean Diet (MedDiet) is associated with reduced risk of cognitive impairment and dementia...
June 7, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28592457/functional-network-integrity-presages-cognitive-decline-in-preclinical-alzheimer-disease
#12
Rachel F Buckley, Aaron P Schultz, Trey Hedden, Kathryn V Papp, Bernard J Hanseeuw, Gad Marshall, Jorge Sepulcre, Emily E Smith, Dorene M Rentz, Keith A Johnson, Reisa A Sperling, Jasmeer P Chhatwal
OBJECTIVE: To examine the utility of resting-state functional connectivity MRI (rs-fcMRI) measurements of network integrity as a predictor of future cognitive decline in preclinical Alzheimer disease (AD). METHODS: A total of 237 clinically normal older adults (aged 63-90 years, Clinical Dementia Rating 0) underwent baseline β-amyloid (Aβ) imaging with Pittsburgh compound B PET and structural and rs-fcMRI. We identified 7 networks for analysis, including 4 cognitive networks (default, salience, dorsal attention, and frontoparietal control) and 3 noncognitive networks (primary visual, extrastriate visual, motor)...
June 7, 2017: Neurology
https://www.readbyqxmd.com/read/28591814/abnormal-gray-matter-shape-thickness-and-volume-in-the-motor-cortico-subcortical-loop-in-idiopathic-rapid-eye-movement-sleep-behavior-disorder-association-with-clinical-and-motor-features
#13
Shady Rahayel, Ronald B Postuma, Jacques Montplaisir, Christophe Bedetti, Simona Brambati, Julie Carrier, Oury Monchi, Pierre-Alexandre Bourgouin, Malo Gaubert, Jean-François Gagnon
Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a major risk factor for Parkinson's disease and dementia with Lewy bodies. Anatomical gray matter abnormalities in the motor cortico-subcortical loop areas remain under studied in iRBD patients. We acquired T1-weighted images and administrated quantitative motor tasks in 41 patients with polysomnography-confirmed iRBD and 41 healthy subjects. Cortical thickness and voxel-based morphometry (VBM) analyses were performed to investigate local cortical thickness and gray matter volume changes, vertex-based shape analysis to investigate shape of subcortical structures, and structure-based volumetric analyses to investigate volumes of subcortical and brainstem structures...
June 7, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28590490/synthesis-resolution-and-in-vitro-evaluation-of-three-vesicular-acetylcholine-transporter-ligands-and-evaluation-of-the-lead-fluorine-18-radioligand-in-a-nonhuman-primate
#14
Xuyi Yue, Hongjun Jin, Hui Liu, Zonghua Luo, Xiang Zhang, Kota Kaneshige, Hubert P Flores, Joel S Perlmutter, Stanley M Parsons, Zhude Tu
The vesicular acetylcholine transporter (VAChT) is a reliable biomarker for assessing cholinergic dysfunction associated with dementia. We recently reported three new potent and selective carbon-11 labeled VAChT radiotracers. Herein, we report the resolution with a Chiralcel OD column of three additional fluorine containing VAChT ligands in which a fluoroethoxy or fluoroethylamino moiety was substituted for the methoxy group. An in vitro competitive binding assay showed that (-)-7 had high potency for VAChT (Ki-VAChT = 0...
June 21, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28589565/detailed-analysis-of-the-japanese-version-of-the-rapid-dementia-screening-test-revised-version
#15
Yasushi Moriyama, Aihide Yoshino, Taro Muramatsu, Masaru Mimura
AIM: The number-transcoding task on the Japanese version of the Rapid Dementia Screening Test (RDST-J) requires mutual conversion between Arabic and Chinese numerals (209 to , 4054 to , to 681, to 2027). In this task, question and answer styles of Chinese numerals are written horizontally. We investigated the impact of changing the task so that Chinese numerals are written vertically. METHODS: Subjects were 211 patients with very mild to severe Alzheimer's disease and 42 normal controls...
June 6, 2017: Psychogeriatrics: the Official Journal of the Japanese Psychogeriatric Society
https://www.readbyqxmd.com/read/28586818/association-between-persistent-pain-and-memory-decline-and-dementia-in-a-longitudinal-cohort-of-elders
#16
Elizabeth L Whitlock, L Grisell Diaz-Ramirez, M Maria Glymour, W John Boscardin, Kenneth E Covinsky, Alexander K Smith
Importance: Chronic pain is common among the elderly and is associated with cognitive deficits in cross-sectional studies; the population-level association between chronic pain and longitudinal cognition is unknown. Objective: To determine the population-level association between persistent pain, which may reflect chronic pain, and subsequent cognitive decline. Design, Setting, and Participants: Cohort study with biennial interviews of 10 065 community-dwelling older adults in the nationally representative Health and Retirement Study who were 62 years or older in 2000 and answered pain and cognition questions in both 1998 and 2000...
June 5, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/28582689/the-impact-of-white-matter-lesions-on-the-cognitive-outcome-of-subthalamic-nucleus-deep-brain-stimulation-in-parkinson-s-disease
#17
J Blume, M Lange, E Rothenfusser, C Doenitz, U Bogdahn, A Brawanski, J Schlaier
OBJECTIVES: White Matter lesions (WML) are a risk factor for cognitive impairment in Parkinson's disease. There is no clear evidence of reduced general cognitive function after DBS. However, a subgroup of patients develops dementia rapidly after DBS despite careful patient selection processes. The aim of this study was to evaluate the load of WML as a possible risk factor for cognitive decline following STN DBS. PATIENTS AND METHODS: 40 PD-patients receiving bilateral STN-DBS were followed at least three years after surgery to detect dementia...
May 31, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28578467/demonstration-of-impaired-neurovascular-coupling-responses-in-tg2576-mouse-model-of-alzheimer-s-disease-using-functional-laser-speckle-contrast-imaging
#18
Stefano Tarantini, Gabor A Fulop, Tamas Kiss, Eszter Farkas, Dániel Zölei-Szénási, Veronica Galvan, Peter Toth, Anna Csiszar, Zoltan Ungvari, Andriy Yabluchanskiy
Increasing evidence from epidemiological, clinical, and experimental studies indicates that cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including both vascular cognitive impairment (VCI) and Alzheimer's disease. Vascular contributions to cognitive impairment and dementia (VCID) include impairment of neurovascular coupling responses/functional hyperemia ("neurovascular uncoupling"). Due to the growing interest in understanding and pharmacologically targeting pathophysiological mechanisms of VCID, there is an increasing need for sensitive, easy-to-establish methods to assess neurovascular coupling responses...
June 3, 2017: GeroScience
https://www.readbyqxmd.com/read/28575152/fisetin-reduces-the-impact-of-aging-on-behavior-and-physiology-in-the-rapidly-aging-samp8-mouse
#19
Antonio Currais, Catherine Farrokhi, Richard Dargusch, Aaron Armando, Oswald Quehenberger, David Schubert, Pamela Maher
Alzheimer's disease (AD) is rarely addressed in the context of aging even though there is an overlap in pathology. We previously used a phenotypic screening platform based upon old age-associated brain toxicities to identify the flavonol fisetin as a potential therapeutic for AD and other age-related neurodegenerative diseases. Based on earlier results with fisetin in transgenic AD mice, we hypothesized that fisetin would be effective against brain aging and cognitive dysfunction in rapidly aging SAMP8 mice, a model for sporadic AD and dementia...
June 2, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28556688/severe-and-rapidly-progressive-lafora-disease-associated-with-nhlrc1-mutation-a-case-report
#20
Sara Casciato, Stefano Gambardella, Addolorata Mascia, Pier Paolo Quarato, Alfredo D'Aniello, Yana Ackurina, Veronica Albano, Francesco Fornai, Simona Scala, Giancarlo Di Gennaro
Lafora disease (LD), also known as progressive myoclonic epilepsy-2 (EPM2), is a rare, fatal autosomal recessive disorder typically starting during adolescence in otherwise neurologically normal individuals. It is clinically characterized by insidious of progressive neurological features including seizures, action myoclonus, visual hallucination, ataxia and dementia. Mutations in the laforin (EPM2A) gene on chromosome 6q24 or in the malin gene (NHLRC1) on chromosome 6p22 are responsible of LD phenotype. Diagnostic workup includes genetic analysis as well as axillary skin biopsy with evidence of typical periodic acid-Schiff (PAS)-positive polyglucosan inclusion bodies (Lafora bodies) in the apocrine glands and/or in the eccrine duct...
June 12, 2017: International Journal of Neuroscience
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