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https://www.readbyqxmd.com/read/29792826/fast-evolving-human-specific-neural-enhancers-are-associated-with-aging-related-diseases
#1
Han Chen, Chunyan Li, Zhicheng Zhou, Han Liang
The antagonistic pleiotropy theory hypothesizes that evolutionary adaptations maximizing the fitness in early age increase disease burden after reproduction. This theory remains largely untested at the molecular level. Here, we analyzed enhancer evolution in primates to investigate the relationships between aging-related diseases and enhancers acquired after the human-chimpanzee divergence. We report a 5-fold increased evolutionary rate of enhancers that are activated in neural tissues, leading to fixation of ∼100 human-specific enhancers potentially under adaptation...
May 23, 2018: Cell Systems
https://www.readbyqxmd.com/read/29791460/are-saving-appearance-responses-typical-communication-patterns-in-alzheimer-s-disease
#2
Masateru Matsushita, Yusuke Yatabe, Asuka Koyama, Akiko Katsuya, Daisuke Ijichi, Yusuke Miyagawa, Hiroto Ikezaki, Noboru Furukawa, Manabu Ikeda, Mamoru Hashimoto
INTRODUCTION: To keep up appearances, people with dementia sometimes pretend to know the correct answer, as seen during administration of neuropsychological tests such as the Mini-Mental State Examination (MMSE). These saving appearance responses (SARs) of people with dementia often lead to caregivers and/or medical staff underestimating the severity of dementia and impede proper early initiation of treatment. However, most descriptions of SARs are based on empirical knowledge of clinicians...
2018: PloS One
https://www.readbyqxmd.com/read/29789529/inhibiting-p38-mapk-alpha-rescues-axonal-retrograde-transport-defects-in-a-mouse-model-of-als
#3
Katherine L Gibbs, Bernadett Kalmar, Elena R Rhymes, Alexander D Fellows, Mahmood Ahmed, Paul Whiting, Ceri H Davies, Linda Greensmith, Giampietro Schiavo
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the degeneration of upper and lower motor neurons. Defects in axonal transport have been observed pre-symptomatically in the SOD1G93A mouse model of ALS, and have been proposed to play a role in motor neuron degeneration as well as in other pathologies of the nervous system, such as Alzheimer's disease and hereditary neuropathies. In this study, we screen a library of small-molecule kinase inhibitors towards the identification of pharmacological enhancers of the axonal retrograde transport of signalling endosomes, which might be used to normalise the rate of this process in diseased neurons...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29784843/high-dose-and-delayed-treatment-with-bile-acids-ineffective-in-rml-prion-infected-mice
#4
Grant Norman, Jody Campeau, Valerie L Sim
Prion diseases are a group of neurodegenerative diseases associated with the misfolding of the cellular prion protein (PrPC ) into the infectious form (PrPSc ). There are currently no treatments for prion disease. Bile acids have the ability to protect hepatocytes from apoptosis and are neuroprotective in animal models of other protein folding neurodegenerative diseases including Huntington's, Parkinson's, and Alzheimer's disease. Importantly, bile acids are approved for clinical use in patients with cirrhosis, and have recently been shown to be safe and possibly effective in pilot trials of patients with amyotrophic lateral sclerosis (ALS)...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784049/identification-and-therapeutic-modulation-of-a-pro-inflammatory-subset-of-disease-associated-microglia-in-alzheimer-s-disease
#5
Srikant Rangaraju, Eric B Dammer, Syed Ali Raza, Priyadharshini Rathakrishnan, Hailian Xiao, Tianwen Gao, Duc M Duong, Michael W Pennington, James J Lah, Nicholas T Seyfried, Allan I Levey
BACKGROUND: Disease-associated-microglia (DAM) represent transcriptionally-distinct and neurodegeneration-specific microglial profiles with unclear significance in Alzheimer's disease (AD). An understanding of heterogeneity within DAM and their key regulators may guide pre-clinical experimentation and drug discovery. METHODS: Weighted co-expression network analysis (WGCNA) was applied to existing microglial transcriptomic datasets from neuroinflammatory and neurodegenerative disease mouse models to identify modules of highly co-expressed genes...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29782905/pathology-of-nnos-expressing-gabaergic-neurons-in-mouse-model-of-alzheimer-s-disease
#6
Seungho Choi, Je-Seong Won, Steven L Carroll, Balasubramaniam Annamalai, Inderjit Singh, Avtar K Singh
Alzheimer's disease (AD) is the most common form of dementia that is often accompanied by mood and emotional disturbances and seizures. There is growing body of evidence that neurons expressing γ-aminobutyric acid (GABA) play an important role in regulation of cognition, mood, and emotion as well as seizure susceptibility, but participation of GABAergic neuronal pathology in Alzheimer's disease (AD) is not understood well at present. Here, we report that transgenic mice expressing human amyloid precursor protein Swedish-Deutch-Iowa mutant (APPSweDI ) exhibit early loss of neurons expressing GAD67, a GABA synthesizing enzyme, in advance to the loss of pyramidal neurons in hippocampal CA1 region...
May 18, 2018: Neuroscience
https://www.readbyqxmd.com/read/29782794/peptides-peptidomimetics-and-carbohydrate-peptide-conjugates-as-amyloidogenic-aggregation-inhibitors-for-alzheimer-s-disease
#7
Philip Ryan, Bhautikkumar Patel, Vivek Makwana, Hemant Jadhav, Milton John Kiefel, Andrew Davey, Tristan Reekie, Santosh Rudrawar, Michael Kassiou
Alzheimer's disease (AD) is a progressive neurodegenerative disorder accounting for 60-80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted towards the aggregation of the peptide tau as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed...
May 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29782325/early-emotional-attention-is-impacted-in-alzheimer-s-disease-an-eye-tracking-study
#8
Jessica Bourgin, Nathalie Guyader, Alan Chauvin, Alexandra Juphard, Mathilde Sauvée, Olivier Moreaud, Laetitia Silvert, Pascal Hot
Emotional deficits have been repetitively reported in Alzheimer's disease (AD) without clearly identifying how emotional processing is impaired in this pathology. This paper describes an investigation of early emotional processing, as measured by the effects of emotional visual stimuli on a saccadic task involving both pro (PS) and anti (AS) saccades. Sixteen patients with AD and 25 age-matched healthy controls were eye-tracked while they had to quickly move their gaze toward a positive, negative, or neutral image presented on a computer screen (in the PS condition) or away from the image (in the AS condition)...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782318/amyloid-accumulation-and-cognitive-decline-in-clinically-normal-older-individuals-implications-for-aging-and-early-alzheimer-s-disease
#9
Elizabeth C Mormino, Kathryn V Papp
 The aberrant accumulation of the amyloid protein is a critical and early event in the Alzheimer's disease (AD) cascade. Given the early involvement of this pathological process, it is not surprising that many clinically normal (CN) older individuals demonstrate evidence of abnormal Aβ at postmortem examination and in vivo using either CSF or PET imaging. Converging evidence across multiple research groups suggests that the presence of abnormal Aβ among CN individuals is associated with elevated risk of future clinical impairment and cognitive decline...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782312/naturalistic-driving-study-investigating-self-regulation-behavior-in-early-alzheimer-s-disease-a-pilot-study
#10
Laurence Paire-Ficout, Sylviane Lafont, Fanny Conte, Amandine Coquillat, Colette Fabrigoule, Joël Ankri, Frédéric Blanc, Cécilia Gabel, Jean-Luc Novella, Isabella Morrone, Rachid Mahmoudi
BACKGROUND: Because cognitive processes decline in the earliest stages of Alzheimer's disease (AD), the driving abilities are often affected. The naturalistic driving approach is relevant to study the driving habits and behaviors in normal or critical situations in a familiar environment of participants. OBJECTIVE: This pilot study analyzed in-car video recordings of naturalistic driving in patients with early-stage AD and in healthy controls, with a special focus on tactical self-regulation behavior...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29781669/trajectories-of-irregular-word-reading-ability-as-a-proxy-for-premorbid-intelligence-in-alzheimer-s-disease-mild-cognitive-impairment-and-healthy-aging-a-longitudinal-study
#11
Michael Weinborn, Romola S Bucks, Hamid R Sohrabi, Stephanie R Rainey-Smith, Belinda M Brown, Samantha L Gardener, Aleksandra Gozt, Daniel Christensen, Greg Savage, Simon M Laws, Kevin Taddei, Paul Maruff, Joanne S Robertson, Kathryn A Ellis, David Ames, Colin L Masters, Christopher C Rowe, Ralph N Martins
The ability to read irregularly spelled words is commonly used to estimate premorbid intelligence, as this ability has been thought to be resistant to early effects of neurodegenerative disorders. However, studies evaluating decline of this skill in Alzheimer's disease (AD) have produced conflicting results. Irregular word reading was assessed three times over 36 months in a large (N = 995) sample, including healthy control, AD, and Mild Cognitive Impairment (MCI) groups. At baseline, MCI and AD groups read correctly an average of 3...
May 21, 2018: Psychological Assessment
https://www.readbyqxmd.com/read/29781630/mental-orientation-a-new-approach-to-assessing-patients-across-the-alzheimer-s-disease-spectrum
#12
Gregory Peters-Founshtein, Michael Peer, Yanai Rein, Shlomzion Kahana Merhavi, Zeev Meiner, Shahar Arzy
OBJECTIVE: This study aims to assess the role of mental-orientation in the diagnosis of mild cognitive impairment and Alzheimer's disease using a novel task. METHOD: A behavioral study (Experiment 1) compared the mental-orientation task to standard neuropsychological tests in patients across the Alzheimer's disease spectrum. A functional MRI study (Experiment 2) in young adults compared activations evoked by the mental-orientation and standard-orientation tasks as well as their overlap with brain regions susceptible to Alzheimer's disease pathology...
May 21, 2018: Neuropsychology
https://www.readbyqxmd.com/read/29780876/memory-concerns-in-the-early-alzheimer-s-disease-prodrome-regional-association-with-tau-deposition
#13
Cecily G Swinford, Shannon L Risacher, Arnaud Charil, Adam J Schwarz, Andrew J Saykin
Introduction: Relationship between self- and informant memory concerns and tau aggregation was assessed in adults at risk for Alzheimer's disease (AD). Methods: Regional mean standardized uptake value ratios were extracted from [18 F]flortaucipir positron emission tomography (PET) scans of 82 at-risk adults in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Associations between self- and informant ECog memory scores and tau aggregation were analyzed on both regional and voxelwise bases...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780871/computer-based-evaluation-of-alzheimer-s-disease-and-mild-cognitive-impairment-patients-during-a-picture-description-task
#14
Laura Hernández-Domínguez, Sylvie Ratté, Gerardo Sierra-Martínez, Andrés Roche-Bergua
Introduction: We present a methodology to automatically evaluate the performance of patients during picture description tasks. Methods: Transcriptions and audio recordings of the Cookie Theft picture description task were used. With 25 healthy elderly control (HC) samples and an information coverage measure, we automatically generated a population-specific referent. We then assessed 517 transcriptions (257 Alzheimer's disease [AD], 217 HC, and 43 mild cognitively impaired samples) according to their informativeness and pertinence against this referent...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780870/similar-pattern-of-atrophy-in-early-and-late-onset-alzheimer-s-disease
#15
Carl Eckerström, Niklas Klasson, Erik Olsson, Per Selnes, Sindre Rolstad, Anders Wallin
Introduction: Previous research on structural changes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) have reported inconsistent findings. Methods: In the present substudy of the Gothenburg MCI study, 1.5 T scans were used to estimate lobar and hippocampal volumes using FreeSurfer. Study participants (N = 145) included 63 patients with AD, (24 patients with EOAD [aged ≤65 years], 39 patients with LOAD [aged >65 years]), 25 healthy controls aged ≤65 years, and 57 healthy controls aged >65 years...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780864/change-in-retinal-structural-anatomy-during-the-preclinical-stage-of-alzheimer-s-disease
#16
Cláudia Y Santos, Lenworth N Johnson, Stuart E Sinoff, Elena K Festa, William C Heindel, Peter J Snyder
Introduction: We conducted a 27-month longitudinal study of mid-life adults with preclinical Alzheimer's disease (AD), using spectral domain optical coherence tomography to compare changes in volume and thickness in all retinal neuronal layers to those of age-matched healthy control subjects. Methods: Fifty-six older adults (mean age = 65.36 years) with multiple risk factors for AD completed spectral domain optical coherence tomography retinal imaging and cognitive testing at baseline...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780863/a-novel-cognitive-functional-composite-measure-to-detect-changes-in-early-alzheimer-s-disease-test-retest-reliability-and-feasibility
#17
Roos J Jutten, John Harrison, Philippe R Lee Meeuw Kjoe, Esther M Opmeer, Niki S M Schoonenboom, Frank Jan de Jong, Craig W Ritchie, Philip Scheltens, Sietske A M Sikkes
Introduction: To improve the detection of changes in Alzheimer's disease (AD), we designed the cognitive-functional composite (CFC). As a first validation step, we investigated its test-retest reliability and feasibility of use. Methods: We performed a test-retest study with 2-3 weeks between assessments, including patients with mild cognitive impairment (MCI) or mild AD dementia and cognitively healthy participants. We calculated intraclass correlation coefficients (ICCs) type absolute agreement for all CFC measures and compared baseline and retest scores using paired-samples t -tests...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780862/hospitalization-in-people-with-dementia-with-lewy-bodies-frequency-duration-and-cost-implications
#18
Christoph Mueller, Gayan Perera, Anto P Rajkumar, Manorama Bhattarai, Annabel Price, John T O'Brien, Clive Ballard, Robert Stewart, Dag Aarsland
Introduction: Increased hospitalization is a major component of dementia impact on individuals and cost, but has rarely been studied in dementia with Lewy bodies (DLB). Our aim was to describe the risk and duration of hospital admissions in patients with DLB, and compare these to those in Alzheimer's disease (AD) and the general population. Methods: A large database of mental health and dementia care in South London was used to assemble a cohort of patients diagnosed with DLB...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780861/the-relationship-between-recall-of-recently-versus-remotely-encoded-famous-faces-and-amyloidosis-in-clinically-normal-older-adults
#19
Irina Orlovsky, Willem Huijbers, Bernard J Hanseeuw, Elizabeth C Mormino, Trey Hedden, Rachel F Buckley, Molly LaPoint, Jennifer S Rabin, Dorene M Rentz, Keith A Johnson, Reisa A Sperling, Kathryn V Papp
Introduction: Alzheimer's disease (AD) patients exhibit temporally graded memory loss with remote memories remaining more intact than recent memories. It is unclear whether this temporal pattern is observable in clinically normal adults with amyloid pathology (i.e. preclinical AD). Methods: Participants were asked to recall the names of famous figures most prominent recently (famous after 1990) and remotely (famous from 1960-1980) and were provided with a phonemic cue to ensure that memory failure was not purely due to verbal retrieval weaknesses...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780859/monoaminergic-impairment-in-down-syndrome-with-alzheimer-s-disease-compared-to-early-onset-alzheimer-s-disease
#20
Alain D Dekker, Yannick Vermeiren, Maria Carmona-Iragui, Bessy Benejam, Laura Videla, Ellen Gelpi, Tony Aerts, Debby Van Dam, Susana Fernández, Alberto Lleó, Sebastian Videla, Anne Sieben, Jean-Jacques Martin, Rafael Blesa, Juan Fortea, Peter P De Deyn
Introduction: People with Down syndrome (DS) are at high risk for Alzheimer's disease (AD). Defects in monoamine neurotransmitter systems are implicated in DS and AD but have not been comprehensively studied in DS. Methods: Noradrenaline, adrenaline, and their metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid; and serotonin and its metabolite 5-hydroxyindoleacetic acid were quantified in 15 brain regions of DS without AD (DS, n = 4), DS with AD (DS+AD, n = 17), early-onset AD (EOAD, n = 11) patients, and healthy non-DS controls (n = 10) in the general population...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
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