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https://www.readbyqxmd.com/read/28811267/app-a%C3%AE-structural-diversity-and-alzheimer-s-disease-pathogenesis
#1
REVIEW
Alex E Roher, Tyler A Kokjohn, Steven G Clarke, Michael R Sierks, Chera L Maarouf, Geidy E Serrano, Marwan S Sabbagh, Thomas G Beach
The amyloid cascade hypothesis of Alzheimer's disease (AD) proposes amyloid- β (Aβ) is a chief pathological element of dementia. AD therapies have targeted monomeric and oligomeric Aβ 1-40 and 1-42 peptides. However, alternative APP proteolytic processing produces a complex roster of Aβ species. In addition, Aβ peptides are subject to extensive posttranslational modification (PTM). We propose that amplified production of some APP/Aβ species, perhaps exacerbated by differential gene expression and reduced peptide degradation, creates a diverse spectrum of modified species which disrupt brain homeostasis and accelerate AD neurodegeneration...
August 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28808876/changes-of-cerebrospinal-fluid-a%C3%AE-42-t-tau-and-p-tau-in-parkinson-s-disease-patients-with-cognitive-impairment-relative-to-those-with-normal-cognition-a-meta-analysis
#2
Xiaohui Hu, Yan Yang, Daokai Gong
The cerebrospinal fluid (CSF) signature of reduced amyloid beta 1-42 (Aβ42), elevated total tau (t-tau), and phosphorylated tau181 (p-tau) is important for the early diagnosis of Alzheimer's disease (AD). Aβ42, t-tau, and p-tau have been reported in numerous studies to contribute to predicting cognitive impairment in Parkinson's disease (PDCI). However, no consistent conclusion can be drawn so far. Literatures regarding Aβ42, t-tau, and p-tau in CSF were systematically reviewed, and a meta-analysis was thus performed to evaluate the changes of these biomarkers in PDCI patients, including PD with mild cognitive impairment (PDMCI) and PD dementia (PDD) patients, relative to PD with normal cognition (PDNC) patients...
August 14, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28802934/psychosis-in-parkinson-s-disease
#3
Dominic H Ffytche, Dag Aarsland
Although illusions, hallucinations and delusions did not play a prominent role in James Parkinson's original clinical descriptions, the longitudinal view of disease progression he advocated has important lessons for the study of such symptoms today. A focus on longitudinal progression rather than individual symptoms led to the concept of PD psychosis-a spectrum of positive symptoms in Parkinson's disease. The publication of criteria for PD psychosis in 2007 helped unify the disparate set of symptoms, raising their profile and resulting in a rapid expansion of literature focussing on clinical aspects, mechanisms, and treatment...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28802926/nonmotor-symptoms-and-natural-history-of-parkinson-s-disease-evidence-from-cognitive-dysfunction-and-role-of-noninvasive-interventions
#4
Roberta Biundo, Eleonora Fiorenzato, Angelo Antonini
Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor and nonmotor symptoms (NMS). Several subsequent studies substantiate the great functional burden related to NMS, their progression, and negative effect on quality of life in PD. Additional evidence indicates interesting relationships between striatal dopaminergic function and NMS. The basal ganglia are implicated in the modulation and integration of sensory information and pain, bladder function is under control of both inhibitory (D1) and facilitatory (D2) dopaminergic inputs, finally reduced dopaminergic activity in the mesocortical and mesolimbic pathways is involved in the development of several NMS including mood, motivational, and cognitive alterations...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28802628/physical-activity-domains-and-cognitive-function-over-three-years-in-older-adults-with-subjective-memory-complaints-secondary-analysis-from-the-mapt-trial
#5
Philipe de Souto Barreto, Sandrine Andrieu, Yves Rolland, Bruno Vellas
OBJECTIVES: We aimed to examine the associations of physical activity (PA) domains (i.e., PA in leisure-time (LTPA), for housework (HPA), or for gardening (GPA)) with cognitive function in older adults with subjective memory complaints (no-dementia) and to investigate if those associations were dependent on the status of apolipoprotein E allele 4 (APOE4), omega-3 levels and mild cognitive impairment (MCI). DESIGN: Observational prospective secondary analysis using longitudinal data from a randomized controlled trial...
July 26, 2017: Journal of Science and Medicine in Sport
https://www.readbyqxmd.com/read/28792504/common-gene-network-signature-of-different-neurological-disorders-and-their-potential-implications-to-neuroaids
#6
Vidya Sagar, S Pilakka-Kanthikeel, Paola C Martinez, V S R Atluri, M Nair
The neurological complications of AIDS (neuroAIDS) during the infection of human immunodeficiency virus (HIV) are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s) for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and age macular degeneration...
2017: PloS One
https://www.readbyqxmd.com/read/28781202/biomarkers-for-cognitive-dysfunction-in-parkinson-s-disease
#7
Lorraine V Kalia
INTRODUCTION: Cognitive dysfunction is among the most prevalent and debilitating non-motor features of Parkinson's disease (PD). The neuropathological correlates of cognitive dysfunction in PD are being revealed by clinicopathological correlation studies. These findings are fostering the development of candidate biomarkers to facilitate diagnosis of cognitive impairment and dementia, and to predict cognitive decline and onset of dementia in PD. METHODS: A literature review of candidate biomarkers for cognitive dysfunction in PD was performed based on a PubMed search for peer-reviewed articles published from 1997 to June 2017 using the search terms "biomarker", "parkinson", and "dementia"...
July 24, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28777748/fully-automatic-mri-based-hippocampus-volumetry-using-fsl-first-intra-scanner-test-retest-stability-inter-field-strength-variability-and-performance-as-enrichment-biomarker-for-clinical-trials-using-prodromal-target-populations-at-risk-for-alzheimer-s-disease
#8
Enrica Cavedo, Per Suppa, Catharina Lange, Roland Opfer, Simone Lista, Samantha Galluzzi, Adam J Schwarz, Lothar Spies, Ralph Buchert, Harald Hampel
BACKGROUND: MRI-based hippocampus volume is a core clinical biomarker for identification of Alzheimer's disease (AD). OBJECTIVE: To assess robustness of automatic hippocampus volumetry with the freely available FSL-FIRST software with respect to short-term repeat and across field strength imaging. FSL-FIRST hippocampus volume (FIRST-HV) was also evaluated as enrichment biomarker for mild cognitive impairment (MCI) trials. METHODS: Robustness of FIRST-HV was assessed in 51 healthy controls (HC), 74 MCI subjects, and 28 patients with AD dementia from ADNI1, each with two pairs of back-to-back scans, one at 1...
July 29, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28766695/prevention-of-alzheimer-s-disease-lessons-learned-and-applied
#9
James E Galvin
Alzheimer's disease (AD) affects more than 5 million Americans, with substantial consequences for individuals with AD, families, and society in terms of morbidity, mortality, and healthcare costs. With disease-modifying treatment trials unsuccessful at the present time and only medications to treat symptoms available, an emerging approach is prevention. Advances in diagnostic criteria, biomarker development, and greater understanding of the biophysiological basis of AD make these initiatives feasible. Ongoing pharmacological trials using anti-amyloid therapies are underway in sporadic and genetic forms of AD, although a large number of modifiable risk factors for AD have been identified in observational studies, many of which do not appear to exert effects through amyloid or tau...
August 2, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28756942/identifying-incipient-dementia-individuals-using-machine-learning-and-amyloid-imaging
#10
Sulantha Mathotaarachchi, Tharick A Pascoal, Monica Shin, Andrea L Benedet, Min Su Kang, Thomas Beaudry, Vladimir S Fonov, Serge Gauthier, Pedro Rosa-Neto
Identifying individuals destined to develop Alzheimer's dementia within time frames acceptable for clinical trials constitutes an important challenge to design studies to test emerging disease-modifying therapies. Although amyloid-β protein is the core pathologic feature of Alzheimer's disease, biomarkers of neuronal degeneration are the only ones believed to provide satisfactory predictions of clinical progression within short time frames. Here, we propose a machine learning-based probabilistic method designed to assess the progression to dementia within 24 months, based on the regional information from a single amyloid positron emission tomography scan...
July 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28755001/identification-of-clusters-of-rapid-and-slow-decliners-among-subjects-at-risk-for-alzheimer-s-disease
#11
Dragan Gamberger, Nada Lavrač, Shantanu Srivatsa, Rudolph E Tanzi, P Murali Doraiswamy
The heterogeneity of Alzheimer's disease contributes to the high failure rate of prior clinical trials. We analyzed 5-year longitudinal outcomes and biomarker data from 562 subjects with mild cognitive impairment (MCI) from two national studies (ADNI) using a novel multilayer clustering algorithm. The algorithm identified homogenous clusters of MCI subjects with markedly different prognostic cognitive trajectories. A cluster of 240 rapid decliners had 2-fold greater atrophy and progressed to dementia at almost 5 times the rate of a cluster of 184 slow decliners...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28754803/uric-acid-and-incident-dementia-over-12-years-of-follow-up-a-population-based-cohort-study
#12
Augustin Latourte, Aicha Soumaré, Thomas Bardin, Fernando Perez-Ruiz, Stéphanie Debette, Pascal Richette
OBJECTIVES: In patients with gout, maintaining too low serum uric acid (SUA) level with urate-lowering therapy is a concern because uric acid is thought to be neuroprotective. However, the relation between SUA and dementia remains debated. This study aimed to investigate the impact of SUA level on the incidence of dementia. METHODS: We assessed the longitudinal association between SUA level and incident dementia (Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV) criteria) in a large cohort of healthy older people from the community (Three-City Dijon cohort)...
July 28, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28753016/high-throughput-metabolomics-for-discovering-potential-metabolite-biomarkers-and-metabolic-mechanism-from-the-appswe-ps1de9-transgenic-model-of-alzheimer-s-disease
#13
Jingbo Yu, Ling Kong, Aihua Zhang, Ying Han, Zhidong Liu, Hui Sun, Liang Liu, Xijun Wang
Alzheimer's disease (AD), a neurodegenerative disorder, is the major form of dementia. As AD is an irreversible disease, it is necessary to focus on earlier intervention. However, the potential biomarkers of preclinical AD are still not clear. In this study, urinary metabolomics based on ultra-high-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry was performed for delineating the metabolic changes and potential early biomarkers in APPswe/PS1dE9 (APP/PS1) transgenic mice...
August 16, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28752420/alzheimer-s-disease-csf-biomarkers-clinical-indications-and-rational-use
#14
REVIEW
Ellis Niemantsverdriet, Sara Valckx, Maria Bjerke, Sebastiaan Engelborghs
This review focusses on the validation and standardization of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers, as well as on the current clinical indications and rational use of CSF biomarkers in daily clinical practice. The validated AD CSF biomarkers, Aβ1-42, T-tau, and P-tau181, have an added value in the (differential) diagnosis of AD and related disorders, including mixed pathologies, atypical presentations, and in case of ambiguous clinical dementia diagnosis. CSF biomarkers should not be routinely used in the diagnostic work-up of dementia and cannot be used to diagnose non-AD dementias...
July 27, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28750675/differential-role-of-csf-fatty-acid-binding-protein-3-%C3%AE-synuclein-and-alzheimer-s-disease-core-biomarkers-in-lewy-body-disorders-and-alzheimer-s-dementia
#15
Davide Chiasserini, Leonardo Biscetti, Paolo Eusebi, Nicola Salvadori, Giulia Frattini, Simone Simoni, Naomi De Roeck, Nicola Tambasco, Erik Stoops, Hugo Vanderstichele, Sebastiaan Engelborghs, Brit Mollenhauer, Paolo Calabresi, Lucilla Parnetti
BACKGROUND: Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB) share clinical and molecular features. Cerebrospinal fluid (CSF) biomarkers may help the characterization of these diseases, improving the differential diagnosis. We evaluated the diagnostic performance of five CSF biomarkers across a well-characterized cohort of patients diagnosed with AD, DLB, PDD, and Parkinson's disease (PD). METHODS: A total of 208 patients were enrolled in 3 European centers...
July 28, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28750498/emerging-clinical-issues-and-multivariate-analyses-in-pet-investigations
#16
Javier Arbizu, Alessandro Giuliani, Jaime G Perez-Larraya, Mario Riverol, Cathrine Jonsson, Berta García-García, Maribel Morales, Laura Imaz, Marco Pagani
PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG-PET) has been gradually introduced in the diagnostic clinical criteria of the most prevalent neurodegenerative diseases. Moreover, an increasing amount of literature have shown that the information provided by FDG-PET enhances the sensitivity of standard imaging biomarkers in less frequent disorders in which an early differential diagnosis can be of paramount relevance for patient management and outcome. Therefore emerging uses of FDG-PET may be important in prion diseases, autoimmune encephalitis and amyotrophic lateral sclerosis...
July 27, 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28750495/imaging-biomarkers-in-alzheimer-s-disease-added-value-in-the-clinical-setting
#17
Silvia Morbelli, Matteo Bauckneht, Philip Scheltens
Over the last 20 years the availability of Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) technologies as well as of CerebroSpinal Fluid (CSF) biomarkers has allowed research and clinical approach to Alzheimer's Disease (AD) to move towards the earliest manifestations of the disease. This new approach resulted in an increasing knowledge about in vivo biological and neuropathological processes of each phase of the AD-related damage from preclinical, to mild cognitive impairment, and finally to dementia due to AD...
July 27, 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28743782/-18-f-av-1451-and-csf-t-tau-and-p-tau-as-biomarkers-in-alzheimer-s-disease
#18
Niklas Mattsson, Michael Schöll, Olof Strandberg, Ruben Smith, Sebastian Palmqvist, Philip S Insel, Douglas Hägerström, Tomas Ohlsson, Henrik Zetterberg, Jonas Jögi, Kaj Blennow, Oskar Hansson
To elucidate the relationship between cerebrospinal fluid (CSF) total-tau (T-tau) and phosphorylated tau (P-tau) with the tau PET ligand (18)F-AV-1451 in Alzheimer's disease (AD), we examined 30 cognitively healthy elderly (15 with preclinical AD), 14 prodromal AD, and 39 AD dementia patients. CSF T-tau and P-tau were highly correlated (R = 0.92, P < 0.001), but they were only moderately associated with retention of (18)F-AV-1451, and mainly in demented AD patients. (18)F-AV-1451, but not CSF T-tau or P-tau, was strongly associated with atrophy and cognitive impairment...
July 25, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28735291/subclinical-atherosclerosis-cardiac-and-kidney-function-heart-failure-and-dementia-in-the-very-elderly
#19
Lewis H Kuller, Oscar L Lopez, John S Gottdiener, Dalane W Kitzman, James T Becker, Yuefang Chang, Anne B Newman
BACKGROUND: Heart failure (HF) and dementia are major causes of disability and death among older individuals. Risk factors and biomarkers of HF may be determinants of dementia in the elderly. We evaluated the relationship between biomarkers of cardiovascular disease and HF and risk of dementia and death. Three hypotheses were tested: (1) higher levels of high-sensitivity cardiac troponin T, N-terminal of prohormone brain natriuretic peptide, and cystatin C predict risk of death, cardiovascular disease, HF, and dementia; (2) higher levels of cardiovascular disease biomarkers are associated with increased risk of HF and then secondary increased risk of dementia; and (3) risk of dementia is lower among participants with a combination of lower coronary artery calcium, atherosclerosis, and lower high-sensitivity cardiac troponin T (myocardial injury)...
July 22, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28734089/dementia-risk-and-prevention-by-targeting-modifiable-vascular-risk-factors
#20
REVIEW
Sana Tariq, Philip A Barber
The incidence of dementia is expected to double in the next 20 years and will contribute to heavy social and economic burden. Dementia is caused by neuronal loss that leads to brain atrophy years before symptoms manifest. Currently, no cure exists and extensive efforts are being made to mitigate cognitive impairment in late life in order to reduce the burden on patients, caregivers, and society. The most common type of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) often co-exists in the brain and shares common, modifiable risk factors, which are targeted in numerous secondary prevention trials...
July 22, 2017: Journal of Neurochemistry
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