106,721 results match your criteria Alzheimers & Dementia[Journal]


Refining memory assessment of elderly people with cognitive impairment: Insights from the short-term memory binding test.

Arch Gerontol Geriatr 2019 Apr 1;83:114-120. Epub 2019 Apr 1.

Department of Basic Psychology II (Cognitive Processes), Faculty of Psychology, Complutense University of Madrid, Spain.

Alzheimer's disease (AD) affects temporary memory for bound features more remarkably than for individual features. Such selective impairments manifest from presymptomatic through dementia stages via titration procedures. A recent study suggested that without titration and with high memory load the binding selectivity may disappear in people at risk of AD such as those with Mild Cognitive Impairment (MCI). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01674943193008
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http://dx.doi.org/10.1016/j.archger.2019.03.025DOI Listing
April 2019
1 Read

Akebia Saponin D inhibits the formation of atherosclerosis in ApoE mice by attenuating oxidative stress-induced apoptosis in endothelial cells.

Atherosclerosis 2019 Apr 10;285:23-30. Epub 2019 Apr 10.

Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China. Electronic address:

Background And Aims: Akebia Saponin D (ASD) is a major bioactive triterpenoid saponin compound isolated from the Chinese herb Dipsacus asper wall (DSW). DSW has been long used as an anti-Alzheimer disease and anti-osteoporosis agent in clinics. However, anti-atherosclerotic effects of ASD have not been fully investigated. Read More

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http://dx.doi.org/10.1016/j.atherosclerosis.2019.04.202DOI Listing

Late-Life Environmental Enrichment Preserves Short-Term Memory and May Attenuate Microglia in Male APP/PS1 Mice.

Neuroscience 2019 Apr 15. Epub 2019 Apr 15.

Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Tasmania, 7000, Australia.

Environmental enrichment (EE) has been consistently reported to enhance cognitive function in mouse models of neuropathology. Microglia, implicated in Alzheimer's disease pathology, may mediate this effect. The aim of the present study was to investigate the effect of EE on cognitive function and microglia in mouse models of ageing and amyloidosis. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03064522193025
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http://dx.doi.org/10.1016/j.neuroscience.2019.04.015DOI Listing
April 2019
1 Read

Retinal oximetry: Metabolic imaging for diseases of the retina and brain.

Prog Retin Eye Res 2019 Apr 15. Epub 2019 Apr 15.

University of Iceland, Reykjavik, Iceland.

Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of hemoglobin. The imaging technology is non-invasive and reproducible with remarkably low variability on test-retest studies and in healthy cohorts. Pathophysiological principles and novel biomarkers in several retinal diseases have been discovered, as well as possible applications for systemic and brain disease. Read More

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http://dx.doi.org/10.1016/j.preteyeres.2019.04.001DOI Listing

Herpesviral infections and antimicrobial protection for Alzheimer's disease: Implications for prevention and treatment.

Authors:
Qingsong Qin Yun Li

J Med Virol 2019 Apr 17. Epub 2019 Apr 17.

Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong, China.

Accumulating evidence suggests that infections by herpesviruses might be closely linked to Alzheimer's disease (AD). Pathological hallmarks of AD brains include senile plaques induced by amyloid β peptide (Aβ) in the extracellular space and intracellular neurofibrillary tangles (NFTs) consisting of phosphorylated tau protein. The prevailing hypothesis for the mechanism of AD is amyloid cascade reaction. Read More

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http://dx.doi.org/10.1002/jmv.25481DOI Listing

Site-specific glycations of Aβ1-42 affect fibril formation and are neurotoxic.

J Biol Chem 2019 Apr 17. Epub 2019 Apr 17.

University of Auckland, New Zealand.

Amyloid β1-42 (Aβ1-42) peptide is involved in Alzheimer's disease (AD) pathogenesis and is prone to glycation, an irreversible process resulting in proteins with accumulated advanced glycated end products (AGEs). Nε-(carboxyethyl)lysine (CEL) is a common AD-associated AGE, occurring at either Lys-16 or Lys-28 of Aβ1-42. Methylglyoxal is commonly used for the unspecific glycation of Aβ1-42, which results in a complex mixture of AGE-modified peptides and makes interpretation of a causative AGE at a specific amino acid residue difficult. Read More

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http://www.jbc.org/lookup/doi/10.1074/jbc.RA118.006846
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http://dx.doi.org/10.1074/jbc.RA118.006846DOI Listing
April 2019
1 Read

Poems about Alzheimer disease.

Authors:
Robert Colman

CMAJ 2018 Jun;190(25):E770

Newmarket, Ont.

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http://dx.doi.org/10.1503/cmaj.180424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019342PMC

Oleuropein aglycone and hydroxytyrosol interfere differently with toxic Aβ aggregation.

Food Chem Toxicol 2019 Apr 14. Epub 2019 Apr 14.

Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', University of Florence, Viale Morgagni 50 - 50134, Florence, Italy; Interuniversity Center for the Study of Neurodegenerative Diseases (CIMN), Florence, Italy. Electronic address:

Oleuropein aglycone (OleA), the most abundant polyphenol in extra virgin olive oil (EVOO), and Hydroxythyrosol (HT), the OleA main metabolite, have attracted our interest due to their multitarget effects, including the interference with amyloid aggregation path. However, the mechanistic details of their anti-amyloid effect are not known yet. We report here a broad biophysical approach and cell biology techniques that enabled us to characterize the different molecular mechanisms by which OleA and HT modulate the Aβ fibrillation, a main histopathological feature of Alzheimer's disease (AD). Read More

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http://dx.doi.org/10.1016/j.fct.2019.04.015DOI Listing

Depression in Neurodegenerative Diseases: Common Mechanisms and Current Treatment Options.

Neurosci Biobehav Rev 2019 Apr 14. Epub 2019 Apr 14.

Island Medical Program, University of British Columbia, Victoria, BC, Canada; Division of Medical Sciences, University of Victoria, Victoria, BC, Canada. Electronic address:

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and a major cause of disability worldwide. This neurological condition is commonly associated with neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD), and has a significant impact on the increasing burden of these neuropathologies. Over the past decades, some of the pathophysiological and molecular mechanisms that contribute to these diseases have been elucidated and these findings indicate that, despite presenting distinct features, there are several similarities between the neurobiological alterations that lead to MDD and neurodegeneration in AD, PD and HD. Read More

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http://dx.doi.org/10.1016/j.neubiorev.2019.04.002DOI Listing

Nobiletin Protects Against Systemic Inflammation-Stimulated Memory Impairment via MAPK and NF-κB Signaling Pathways.

J Agric Food Chem 2019 Apr 17. Epub 2019 Apr 17.

Neuroinflammation is intensively demonstrated to be related with various neurodegenerative diseases including Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and Alzheimer disease (AD). As a natural polymethoxylated flavone, Nobiletin (NOB) is reported to alleviate oxidative stress, insulin resistance, and obesity. In this study, we evaluated the protection effects of NOB on neuroinflammation and memory deficit. Read More

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http://dx.doi.org/10.1021/acs.jafc.9b00133DOI Listing

Preparation and Characterization of Curcumin-Loaded Polymeric Nanomicelles to Interference with Amyloidogenesis through Glycation Method.

Biotechnol Appl Biochem 2019 Apr 16. Epub 2019 Apr 16.

Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), P.O. Box 14155-4777, Tehran, Iran.

Amyloid fibrils, including β-amyloid (Aβ) fibrils, are protein aggregates that form under certain conditions, associated with neurodegeneration that interfere with neural synaptic transmission resulting in some neural disorders, such as Alzheimer disease. The aim of this study is to inhibit amyloidogenesis by using preparatory polymeric nanomicelles as therapeutic agents and also as nano carriers for curcumin to target Aβ fibrils through the glycation method of Bovine Serum Albumin (BSA) in the presence of Phosphate Buffer Saline (PBS). Polymeric nanomicelles were prepared from Phosphatidylethanolamine-distearoyl methoxypolyethylene glycol conjugates in the presence and absence of Curcumin and then the morphological and structural characteristics of the nanomicelles were characterized in detail. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bab.1751
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http://dx.doi.org/10.1002/bab.1751DOI Listing
April 2019
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Inflammation in Mild Cognitive Impairment due to Parkinson's disease, Lewy Body disease and Alzheimer's disease.

Int J Geriatr Psychiatry 2019 Apr 16. Epub 2019 Apr 16.

Institute of Neuroscience, Newcastle upon Tyne, United Kingdom.

Background: Inflammation appears to play a role in the progression of neurodegenerative diseases. However, little is known about inflammation during early stages of cognitive decline or whether this differs in different disease groups. We sought to investigate this by assessing the inflammatory profile in patients with Parkinson's disease with the early stages of cognitive impairment (PD-MCI), patients with prodromal Alzheimer's disease (MCI-AD), prodromal Lewy Body disease (MCI-LB) and controls. Read More

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http://dx.doi.org/10.1002/gps.5124DOI Listing
April 2019
2 Reads

Biological Hallmarks of Cancer in Alzheimer's Disease.

Mol Neurobiol 2019 Apr 16. Epub 2019 Apr 16.

Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.

Although Alzheimer's disease (AD) is an international health research priority for our aging population, little therapeutic progress has been made. This lack of progress may be partially attributable to disease heterogeneity. Previous studies have identified an inverse association of cancer and AD, suggesting that cancer history may be one source of AD heterogeneity. Read More

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http://dx.doi.org/10.1007/s12035-019-1591-5DOI Listing
April 2019
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eBrain: a Three Dimensional Simulation Tool to Study Drug Delivery in the Brain.

Authors:
Yaki Setty

Sci Rep 2019 Apr 16;9(1):6162. Epub 2019 Apr 16.

Gateway Institute for Brain Research, 3321 College Avenue, Davie, 33314, Florida, USA.

Neurodegenerative disorders such as Alzheimer's and Parkinson's disease are severe disorders with acute symptoms that gradually progress. In the course of developing disease-modifying treatments for neurodegenerative disorders there is a need to develop novel strategies to increase efficacy of drugs and accelerate the development process. We developed a tool for simulating drug delivery in the brain by translating MRI data into an interactive 3D model. Read More

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http://www.nature.com/articles/s41598-019-42261-3
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http://dx.doi.org/10.1038/s41598-019-42261-3DOI Listing
April 2019
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The effect of ApoE ε4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study.

Neuroimage Clin 2019 Mar 28;22:101795. Epub 2019 Mar 28.

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Nuclear Medicine, Peking University First Hospital, Beijing, China; Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States. Electronic address:

While the ApoE ε4 allele is a known risk factor for mild cognitive impairment (MCI) and Alzheimer's disease, brain region specific effects remain elusive. In this study, we investigate whether the ApoE ε4 allele exhibits brain region specific effects in longitudinal glucose uptake among patients with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed FDG PET images, MRIs, and demographic information were downloaded from the ADNI database. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449776PMC

APOE-ε4 risk variant for Alzheimer's disease modifies the association between cognitive performance and cerebral morphology in healthy middle-aged individuals.

Neuroimage Clin 2019 Apr 8;23:101818. Epub 2019 Apr 8.

Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain; Universitat Pompeu Fabra, Barcelona, Spain. Electronic address:

The APOE-ε4 genotype is the highest genetic risk factor for Alzheimer's disease (AD). In cognitively unimpaired individuals, it has been related to altered brain morphology, function and earlier amyloid beta accumulation. However, its impact on cognitive performance is less evident. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101818DOI Listing

Improvements of Symptoms of Alzheimer`s Disease by Inhibition of the Angiotensin System.

Pharmacol Res 2019 Apr 13. Epub 2019 Apr 13.

Molecular Pharmacology, Department of Chemistry and Applied Biosciences, ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.

With ageing of the global society, the frequency of ageing-related neurodegenerative diseases such as Alzheimer`s disease (AD) is on the rise worldwide. Currently, there is no cure for AD, and the four drugs approved for AD only have very small effects on AD symptoms. Consequently, there are enormous efforts worldwide to identify new targets for treatment of AD. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10436618183195
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http://dx.doi.org/10.1016/j.phrs.2019.04.014DOI Listing
April 2019
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Deciphering the "elixir of life": Dynamic perspectives into the allosteric modulation of mitochondrial ATP synthase by J147, a novel drug in the treatment of Alzheimer's disease.

Chem Biodivers 2019 Apr 16. Epub 2019 Apr 16.

University of KwaZulu-Natal, Westville, School of Health Sciences, School of Health Sciences, University of, Not Available, 4001, Durban, SOUTH AFRICA.

The discovery of J147 represented a significant milestone in the treatment of age-related disorders, which was further augmented by the recent identification of mitochondrial ATP synthase as the therapeutic target. However, the underlying molecular events associated with the modulatory activity of J147 has remained unresolved till date. Herein, we present, for the first time, a dynamical approach to investigate the allosteric regulation of mATP synthase by J147, using a reliable human αγβ protein model. Read More

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http://dx.doi.org/10.1002/cbdv.201900085DOI Listing
April 2019
1 Read
1.515 Impact Factor

Peri-Infarct Upregulation of the Oxytocin Receptor in Vascular Dementia.

J Neuropathol Exp Neurol 2019 May;78(5):436-452

Department of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, Michigan.

Vascular dementia (VaD) is cognitive decline linked to reduced cerebral blood perfusion, yet there are few therapeutic options to protect cognitive function following cerebrovascular accidents. The purpose of this study was to profile gene expression changes unique to VaD to identify and characterize disease relevant changes that could offer clues for future therapeutic direction. Microarray-based profiling and validation studies of postmortem frontal cortex samples from VaD, Alzheimer disease, and age-matched control subjects revealed that the oxytocin receptor (OXTR) was strongly and differentially upregulated in VaD. Read More

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http://dx.doi.org/10.1093/jnen/nlz023DOI Listing

Profiling of acetylcholinesterase inhibitory alkaloids from some Crinum, Habranthus and Zephyranthes species by GC-MS combined with multivariate analyses and in silico studies.

Nat Prod Res 2019 Apr 16:1-8. Epub 2019 Apr 16.

b Chemistry Departament , Federal University of Espírito Santo , Vitória , ES , Brazil.

Acetylcholinesterase (AChE) inhibitors remain the class of drugs used for the treatment of Alzheimer disease (AD). For the aim of discovering new sources of potent AChE inhibitors, a combined AChE-inhibitory activity together with alkaloid profiles by GC-MS, combined with multivariate statistical analysis for biomarkers determination and in silico studies were attempted. Strategy was applied on leaves, roots and bulbs of six aquatic and terrestrial Amaryllidaceae species. Read More

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http://dx.doi.org/10.1080/14786419.2019.1598989DOI Listing

Amyloid-β Oligomers Regulate ADAM10 Synaptic Localization Through Aberrant Plasticity Phenomena.

Mol Neurobiol 2019 Apr 13. Epub 2019 Apr 13.

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.

A disintegrin and metalloproteinase 10 (ADAM10) is a synaptic enzyme that has been previously shown to limit amyloid-β (Aβ) peptide formation in Alzheimer's disease (AD). Furthermore, ADAM10 participates to spine shaping through the cleavage of adhesion molecules and its activity is under the control of synaptic plasticity events. In particular, long-term depression (LTD) promotes ADAM10 synaptic localization triggering its forward trafficking to the synapse, while long-term potentiation elicits ADAM10 internalization. Read More

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http://link.springer.com/10.1007/s12035-019-1583-5
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http://dx.doi.org/10.1007/s12035-019-1583-5DOI Listing
April 2019
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Protective role of phenylethanoid glycosides, Torenoside B and Savatiside A, in Alzheimer's disease.

Exp Ther Med 2019 May 7;17(5):3755-3767. Epub 2019 Mar 7.

College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu 215000, P.R. China.

The current study assessed the efficacy of two phenylethanoid glycosides (PhGs), Torenoside B (TB) and Savatiside A (SA), in the treatment of Alzheimer's disease (AD). The effects of TB and SA compounds were first assessed following amyloid beta (Aβ) induction in SH-SY5Y cells at a range of concentrations. Their effects on cell viability and reactive oxygen species (ROS) were determined by performing MTT and dichlorofluorescin diacetate assays, respectively. Read More

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http://dx.doi.org/10.3892/etm.2019.7355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447766PMC
May 2019
1 Read

Diagnostic Work-Up Is More Complete in Rural than in Urban Areas for Patients with Dementia: Results of a Swedish Dementia Registry Study.

J Alzheimers Dis 2019 Apr 12. Epub 2019 Apr 12.

Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Background: Life in rural areas differs from life in urban areas not only in geographical conditions, but also in health care structure.

Objective: Our aim is to compare the diagnostic process and the management of dementia in rural and urban areas of Sweden.

Methods: We performed a cross-sectional study of patients with dementia living in rural (n = 16,428), intermediate (n = 18,033), and urban (n = 23,680) areas in Sweden including patients registered from 2007 through 2014 in the Swedish Dementia Registry (SveDem). Read More

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http://dx.doi.org/10.3233/JAD-190017DOI Listing
April 2019
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Effects of anti-inflammatory and adaptogenic herbal extracts on gene expression of eicosanoids signaling pathways in isolated brain cells.

Phytomedicine 2019 Mar 10:152881. Epub 2019 Mar 10.

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany. Electronic address:

Introduction: The adaptogens modulate expression of genes playing key roles in development of aging-related disorders, which are considered as low-grade systemic inflammatory conditions characterized by an imbalance between pro-and anti-inflammatory eicosanoids.

Aim Of The Study: We compared the effects of anti-inflammatory and adaptogenic plant extracts on the expression of genes involved in biosynthesis of eicosanoids with the purpose to find those plants, which selectively upregulated the expression of anti-inflammatory lipoxins signaling pathways and inhibited pro-inflammatory signaling pathways associated with biosynthesis of leukotrienes, prostaglandins and thromboxanes.

Materials And Methods: We conducted transcriptome-wide RNA sequencing to profile gene expression alterations in T98G neuroglia cells upon treatment of plant extract and analyzed the relevance of deregulated genes to eicosanoids signaling pathways using in silico models. Read More

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http://dx.doi.org/10.1016/j.phymed.2019.152881DOI Listing

Reduction of aluminum ion neurotoxicity through a small peptide application - NAP treatment of Alzheimer's disease.

J Food Drug Anal 2019 Apr 12;27(2):551-564. Epub 2019 Jan 12.

Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 804, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. Electronic address:

Alzheimer's disease (AD) is the most common cause of dementia in late life. It is difficult to precisely diagnose AD at early stages, making biomarker search essential for further developments. The objective of this study was to identify protein biomarkers associated with aluminum ions toxicity (AD-like toxicity) in a human neuroblastoma cell model, SH-SY5Y and assess potential prevention by NAP (NAPVSIPQ). Read More

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http://dx.doi.org/10.1016/j.jfda.2018.11.009DOI Listing
April 2019
2 Reads
0.395 Impact Factor

Personalized risk for clinical progression in cognitively normal subjects-the ABIDE project.

Alzheimers Res Ther 2019 Apr 16;11(1):33. Epub 2019 Apr 16.

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

Background: Biomarkers such as cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) have predictive value for progression to dementia in patients with mild cognitive impairment (MCI). The pre-dementia stage takes far longer, and the interpretation of biomarker findings is particular relevant for individuals who present at a memory clinic, but are deemed cognitively normal. The objective of the current study is to construct biomarker-based prognostic models for personalized risk of clinical progression in cognitively normal individuals presenting at a memory clinic. Read More

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https://alzres.biomedcentral.com/articles/10.1186/s13195-019
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http://dx.doi.org/10.1186/s13195-019-0487-yDOI Listing
April 2019
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Intravenous Immunoglobulin for Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Am J Alzheimers Dis Other Demen 2019 Apr 15:1533317519843720. Epub 2019 Apr 15.

1 Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece.

Aim: To assess the efficacy and safety of intravenous immunoglobulin (IVIg) for patients with Alzheimer's disease (AD).

Materials And Methods: We searched electronic databases and other sources for randomized controlled trials comparing IVIg with placebo or other treatment for adults with AD. Primary outcome was change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Read More

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http://dx.doi.org/10.1177/1533317519843720DOI Listing

Scam Awareness Related to Incident Alzheimer Dementia and Mild Cognitive Impairment: A Prospective Cohort Study.

Ann Intern Med 2019 Apr 16. Epub 2019 Apr 16.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois (P.A.B., L.Y., J.A.S., R.S.W., D.A.B.).

Background: Decreased scam awareness may be an early indicator of impending Alzheimer dementia and its precursor, mild cognitive impairment, but prior studies have not systematically examined the associations between scam awareness and adverse cognitive outcomes.

Objective: To test the hypothesis that low scam awareness is associated with increased risk for incident Alzheimer dementia, mild cognitive impairment, and Alzheimer disease pathology in the brain.

Design: Prospective cohort study of aging. Read More

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http://dx.doi.org/10.7326/M18-2711DOI Listing

No synergistic effect of subtherapeutic doses of donepezil and EVP-6124 in healthy elderly subjects in a scopolamine challenge model.

Alzheimers Dement (N Y) 2019 1;5:89-98. Epub 2019 Apr 1.

Centre for Human Drug Research, Leiden, the Netherlands.

Introduction: Donepezil is a widely used cholinesterase inhibitor in the management of Alzheimer's disease. Despite large-scaled evidence for its efficacy, elevated peripheral ACh levels often lead to side effects and are dose limiting. The present exploratory study is designed to determine the potentiation of the effects of donepezil by cotreatment with EVP-6124, an alpha-7 nicotinic agonist, to reduce scopolamine-induced cognitive deficits in healthy elderly subjects. Read More

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http://dx.doi.org/10.1016/j.trci.2019.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446049PMC

Neuroimaging biomarkers for clinical trials in atypical parkinsonian disorders: Proposal for a Neuroimaging Biomarker Utility System.

Alzheimers Dement (Amst) 2019 Dec 2;11:301-309. Epub 2019 Apr 2.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Introduction: Therapeutic strategies targeting protein aggregations are ready for clinical trials in atypical parkinsonian disorders. Therefore, there is an urgent need for neuroimaging biomarkers to help with the early detection of neurodegenerative processes, the early differentiation of the underlying pathology, and the objective assessment of disease progression. However, there currently is not yet a consensus in the field on how to describe utility of biomarkers for clinical trials in atypical parkinsonian disorders. Read More

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http://dx.doi.org/10.1016/j.dadm.2019.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446052PMC
December 2019

Preanalytical sample handling recommendations for Alzheimer's disease plasma biomarkers.

Alzheimers Dement (Amst) 2019 Dec 2;11:291-300. Epub 2019 Apr 2.

Research and Development, Roche Diagnostics GmbH, Penzberg, Germany.

Introduction: We examined the influence of common preanalytical factors on the measurement of Alzheimer's disease-specific biomarkers in human plasma.

Methods: Amyloid β peptides (Aβ[1-40], Aβ[1-42]) and total Tau plasma concentrations were quantified using fully automated Roche Elecsys assays.

Results: Aβ(1-40), Aβ(1-42), and total Tau plasma concentrations were not affected by up to three freeze/thaw cycles, up to five tube transfers, the collection tube material, or the size; circadian rhythm had a minor effect. Read More

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http://dx.doi.org/10.1016/j.dadm.2019.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446057PMC
December 2019

No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors.

Transl Neurodegener 2019 3;8:11. Epub 2019 Apr 3.

1Department of Neurology, University Hospital Schleswig Holstein, Arnold-Heller Str. 3, 24105 Kiel, Germany.

Background: IgG-class autoantibodies to N-Methyl-D-Aspartate (NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis. Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results. We measured NMDA antibodies in a large, well phenotyped sample of Parkinson patients without and with cognitive impairment ( = 296) and controls ( = 295) free of neuropsychiatric disease. Read More

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https://translationalneurodegeneration.biomedcentral.com/art
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http://dx.doi.org/10.1186/s40035-019-0153-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446289PMC
April 2019
1 Read

Association Between Polymorphisms and Risk of Alzheimer's Disease and Parkinson's Disease: A Meta-Analysis Based on 5,315 Individuals.

Front Neurol 2019 28;10:290. Epub 2019 Mar 28.

Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

A number of studies have reported that aldehyde dehydrogenase-2 () polymorphisms maybe associated with the risk of Alzheimer's disease (AD) and Parkinson's disease (PD). However, the results of such studies are inconsistent. We therefore conducted a meta-analysis to clarify the association between polymorphisms and the risk of AD and PD. Read More

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http://dx.doi.org/10.3389/fneur.2019.00290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448532PMC

Biomarker-Drug and Liquid Biopsy Co-development for Disease Staging and Targeted Therapy: Cornerstones for Alzheimer's Precision Medicine and Pharmacology.

Front Pharmacol 2019 29;10:310. Epub 2019 Mar 29.

AXA Research Fund & Sorbonne University Chair, Paris, France.

Systems biology studies have demonstrated that different (epi)genetic and pathophysiological alterations may be mapped onto a single tumor's clinical phenotype thereby revealing commonalities shared by cancers with divergent phenotypes. The success of this approach in cancer based on analyses of traditional and emerging body fluid-based biomarkers has given rise to the concept of liquid biopsy enabling a non-invasive and widely accessible precision medicine approach and a significant paradigm shift in the management of cancer. Serial liquid biopsies offer clues about the evolution of cancer in individual patients across disease stages enabling the application of individualized genetically and biologically guided therapies. Read More

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http://dx.doi.org/10.3389/fphar.2019.00310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450260PMC

Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Front Aging Neurosci 2019 29;11:61. Epub 2019 Mar 29.

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.

Previous studies found inconsistent results for the relationship between Alzheimer's disease and the levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate. This study performed a systematic review and meta-analysis to evaluate previous studies' results on this relationship. Studies related to this outcome were obtained using a systematic search from the electronic databases of PubMed, Embase, Web of Science, and Psyc-ARTICLES in March 2018. Read More

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http://dx.doi.org/10.3389/fnagi.2019.00061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449476PMC
March 2019
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Trajectories of the Hippocampal Subfields Atrophy in the Alzheimer's Disease: A Structural Imaging Study.

Front Neuroinform 2019 22;13:13. Epub 2019 Mar 22.

Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.

Background: The hippocampus and hippocampal subfields have been found to be diversely affected in Alzheimer's Disease (AD) and early stages of Alzheimer's disease by neuroimaging studies. However, our knowledge is still lacking about the trajectories of the hippocampus and hippocampal subfields atrophy with the progression of Alzheimer's disease.

Objective: To identify which subfields of the hippocampus differ in the trajectories of Alzheimer's disease by magnetic resonance imaging (MRI) and to determine whether individual differences on memory could be explained by structural volumes of hippocampal subfields. Read More

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http://dx.doi.org/10.3389/fninf.2019.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450438PMC
March 2019
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MIC-MAC: An automated pipeline for high-throughput characterization and classification of three-dimensional microglia morphologies in mouse and human postmortem brain samples.

Glia 2019 Apr 14. Epub 2019 Apr 14.

Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg.

The phenotypic changes of microglia in brain diseases are particularly diverse and their role in disease progression, beneficial, or detrimental, is still elusive. High-throughput molecular approaches such as single-cell RNA-sequencing can now resolve the high heterogeneity in microglia population for a specific physiological condition, however, the relation between the different microglial signatures and their surrounding brain microenvironment is barely understood. Thus, better tools to characterize the phenotypic variations of microglia in situ are needed, particularly for human brain postmortem samples analysis. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/glia.23623
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http://dx.doi.org/10.1002/glia.23623DOI Listing
April 2019
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Risk Aversion and Alzheimer Disease in Old Age.

Am J Geriatr Psychiatry 2019 Feb 21. Epub 2019 Feb 21.

Behavioral Sciences (RSW, PAB).

Objective: To test the hypothesis that late-life risk aversion is partly a prodromal sign of dementia.

Methods: The authors' design was a longitudinal clinical-pathologic cohort study. The setting included participants' residences in the Chicago area, and a total of 874 older persons without dementia were enrolled. Read More

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http://dx.doi.org/10.1016/j.jagp.2019.02.011DOI Listing
February 2019

M1 Muscarinic Receptor Activation Rescues β-Amyloid-Induced Cognitive Impairment through AMPA Receptor GluA1 Subunit.

Neuroscience 2019 Apr 11. Epub 2019 Apr 11.

Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

M1 muscarinic receptors have long been identified as a potential therapeutic target for the treatment of cognitive impairment in Alzheimer's disease (AD). Our previous study has shown that M1 receptors promote membrane insertion and synaptic delivery of AMPA receptor GluA1 subunit. In this study, we sought to determine whether activation of M1 receptor would rescue the cognitive impairment in AD model mice through modulation of GluA1 subunit. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03064522193024
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http://dx.doi.org/10.1016/j.neuroscience.2019.04.007DOI Listing
April 2019
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Differences in cortical perfusion detected by arterial spin labeling in nonamnestic and amnestic subtypes of early-onset Alzheimer's disease.

J Neuroradiol 2019 Apr 11. Epub 2019 Apr 11.

U1171. In-vivo Imaging Platform, Predictive Medicine and Therapeutic Research Institute, Université Lille Nord de France, Lille, France; Department of Neuroradiology, CHU Lille, Lille, France.

Objectives: Early-onset Alzheimer's disease (EOAD) begins before the age of 65 and is characterized by a faster clinical course and the frequency of nonamnestic symptoms compared to late onset Alzheimer disease (LOAD). However, the pathophysiological process of EOAD remains unclear. We expected that ASL may show widespread cortical hypoperfusion in EOAD compared to LOAD and in nonamnestic EOAD compared to amnestic EOAD. Read More

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http://dx.doi.org/10.1016/j.neurad.2019.03.017DOI Listing

Quantitative assessment of oligomeric amyloid beta peptide binding to alpha7 nicotinic receptor.

Br J Pharmacol 2019 Apr 13. Epub 2019 Apr 13.

Inserm U1016, Institut Cochin, Paris, 75014, France.

Background And Purpose: Progressive dysfunction of cholinergic transmission is a well-known characteristic of Alzheimer's Disease (AD). Amyloid beta (Aβ) peptide oligomers are known to play a central role in AD and are suggested to impair the function of the nicotinic acetylcholine receptor alpha 7 (α7nAChR). However, the mechanism underlying the effect of Aβ on α7nAChR function is not fully understood, limiting the therapeutic exploration of this observation in AD. Read More

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http://dx.doi.org/10.1111/bph.14688DOI Listing

Exercise as a potential modulator of inflammation in patients with Alzheimer's disease measured in cerebrospinal fluid and plasma.

Exp Gerontol 2019 Apr 10. Epub 2019 Apr 10.

Danish Dementia Research Centre, Department of Neurology, Rigshospitalet University of Copenhagen, DK-2100 Copenhagen, Denmark. Electronic address:

Background: Neuroinflammation is recognized as part of the pathological progression of Alzheimer's disease (AD), but the molecular mechanisms are still not entirely clear. Systemically, physical exercise has shown to have a positive modulating effect on markers of inflammation. It is not known if this general effect also takes place in the central nervous system in AD. Read More

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http://dx.doi.org/10.1016/j.exger.2019.04.003DOI Listing

Cognitive Decline, Cerebral-Spleen Tryptophan Metabolism, Oxidative Stress, Cytokine Production, and Regulation of the Txnip Gene in 3xTg-AD Mice.

Am J Pathol 2019 Apr 10. Epub 2019 Apr 10.

Department of Psychology and Neuroscience; Department of Psychiatry; Department of Pathology; Brain Repair Centre, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address:

Pathological inflammation in response to injury, infection, or oxidative stress is a proposed mechanism relating cognitive decline to dementia. The kynurenine pathway and thioredoxin-interacting protein (TXNIP) activity regulate inflammation and neurotoxicity in Alzheimer disease (AD). We examined cognitive deficits, kynurenine pathway mediators, TXNIP, and oxidative damage in the cerebrum and spleen, as well as inflammatory cytokine production by stimulated splenocytes, from female 3xTg-AD mice in early and late stages of disease progression. Read More

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http://dx.doi.org/10.1016/j.ajpath.2019.03.006DOI Listing
April 2019
4.591 Impact Factor

Dementia: Paradigm shifting into high gear.

Alzheimers Dement 2019 Apr 9. Epub 2019 Apr 9.

Schulich School of Medicine & Dentistry, Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada. Electronic address:

Redressing the rising threat of dementia demands not only an increase, but a diversification of efforts. We need new approaches, trials, and partners. We cannot afford to continue to only round up the usual suspects, β amyloid, and tau and try to stop them with a single drug "silver bullet". Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15525260193002
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http://dx.doi.org/10.1016/j.jalz.2019.01.006DOI Listing
April 2019
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C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition.

Neurobiol Aging 2019 Mar 11. Epub 2019 Mar 11.

Molecular Neurology, Research Programs Unit, Department of Neurology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.02.026DOI Listing

Identification of genetic heterogeneity of Alzheimer's disease across age.

Neurobiol Aging 2019 Mar 12. Epub 2019 Mar 12.

Center for Multimodal Imaging and Genetics, Department of Radiology, University of California, San Diego, CA, USA. Electronic address:

The risk of APOE for Alzheimer's disease (AD) is modified by age. Beyond APOE, the polygenic architecture may also be heterogeneous across age. We aim to investigate age-related genetic heterogeneity of AD and identify genomic loci with differential effects across age. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.02.022DOI Listing
March 2019
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Application of Artificial Neural Networks to Identify Alzheimer's Disease Using Cerebral Perfusion SPECT Data.

Int J Environ Res Public Health 2019 Apr 11;16(7). Epub 2019 Apr 11.

Department of Anatomy and Neurobiology, Medical University of Gdańsk, 1 Debinki St., 80-211 Gdańsk, Poland.

The aim of this study was to demonstrate the usefulness of artificial neural networks in Alzheimer disease diagnosis (AD) using data of brain single photon emission computed tomography (SPECT). The results were compared with discriminant analysis. The study population consisted of 132 clinically diagnosed patients. Read More

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http://dx.doi.org/10.3390/ijerph16071303DOI Listing

CSF glial biomarkers YKL40 and sTREM2 are associated with longitudinal volume and diffusivity changes in cognitively unimpaired individuals.

Neuroimage Clin 2019 Apr 1;23:101801. Epub 2019 Apr 1.

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Neurology Department, Hospital Clínic i Provincial de Barcelona, Barcelona, Spain; Universitat Pompeu Fabra, Spain; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain. Electronic address:

Cerebrospinal fluid (CSF) YKL40 and sTREM2 are astroglial and microglial activity biomarkers, respectively. We assessed whether CSF YKL40 and sTREM2 baseline levels are associated with longitudinal brain volume and diffusivity changes in cognitively unimpaired adults. Two brain MRI scans of 36 participants (57 to 78-years old, 12 male) were acquired in a 2-year interval. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101801DOI Listing
April 2019
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Plasma metabolomics in early Alzheimer's disease patients diagnosed with amyloid biomarker.

J Proteomics 2019 Apr 9;200:144-152. Epub 2019 Apr 9.

Neonatal Research Unit, Health Research Institute La Fe, Valencia, Spain. Electronic address:

An untargeted metabolomics study has been carried out using plasma samples from patients with Mild Cognitive Impairment due to Alzheimer's disease patients (MCI-AD, n = 29) and healthy people (n = 29)). They have been classified following the National Institute on Aging and Alzheimer's Association (NIA-AA) recommendations and cerebrospinal fluid biomarkers. The analytical method was based on liquid chromatography coupled to high resolution mass spectrometry. Read More

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http://dx.doi.org/10.1016/j.jprot.2019.04.008DOI Listing
April 2019
4 Reads