97,811 results match your criteria Alzheimer's Research & Therapy [Journal]


Metal based donepezil analogues designed to inhibit human acetylcholinesterase for Alzheimer's disease.

PLoS One 2019 20;14(2):e0211935. Epub 2019 Feb 20.

Division of Computer-Aided Drug Design, The Red-Green Research Centre, Dhaka, Bangladesh.

Among neurodegenerative disorders, Alzheimer's disease (AD) is one of the most common disorders showing slow progressive cognitive decline. Targeting acetylcholinesterase (AChE) is one of the major strategies for AD therapeutics, as cholinergic pathways in the cerebral cortex and basal forebrain are compromised. Herein, we report the design of some copper and other metal based donepezil derivatives, employing density functional theory (DFT). Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211935PLOS
February 2019

Potential Diagnostic Imaging of Alzheimer's Disease with Copper-64 Complexes That Bind to Amyloid-β Plaques.

Inorg Chem 2019 Feb 20. Epub 2019 Feb 20.

Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences , Monash University , Parkville , Victoria , Australia , 3052.

Amyloid-β plaques, consisting of aggregated amyloid-β peptides, are one of the pathological hallmarks of Alzheimer's disease. Copper complexes formed using positron-emitting copper radionuclides that cross the blood-brain barrier and bind to specific molecular targets offer the possibility of noninvasive diagnostic imaging using positron emission tomography. New thiosemicarbazone-pyridylhydrazone based ligands that incorporate pyridyl-benzofuran functional groups designed to bind amyloid-β plaques have been synthesized. Read More

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http://dx.doi.org/10.1021/acs.inorgchem.8b03466DOI Listing
February 2019

Food additive dye (quinoline yellow) promotes unfolding and aggregation of myoglobin: A spectroscopic and molecular docking analysis.

Spectrochim Acta A Mol Biomol Spectrosc 2019 Feb 13;214:216-226. Epub 2019 Feb 13.

Department of Chemistry, Collage of Science Princess Noura Bint Abdul Rahman University, Riyadh, Saudi Arabia. Electronic address:

Protein aggregation leads to vast conformational changes and plays a key role in the pathogenesis of various neurodegenerative diseases including Alzheimer's and Parkinson's. In the current piece of work, we have explored the interaction of quinoline yellow (QY) with myoglobin (Mb) at two different pH (3.5 and 7. Read More

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http://dx.doi.org/10.1016/j.saa.2019.01.090DOI Listing
February 2019

Kibra Modulates Learning and Memory via Binding to Dendrin.

Cell Rep 2019 Feb;26(8):2064-2077.e7

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address:

Kibra is a synaptic scaffold protein regulating learning and memory. Alterations of Kibra-encoding gene WWC1 cause various neuronal disorders, including Alzheimer's disease and Tourette syndrome. However, the molecular mechanism underlying Kibra's function in neurons is poorly understood. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.01.097DOI Listing
February 2019

Association between circadian rhythms and neurodegenerative diseases.

Lancet Neurol 2019 Mar 12;18(3):307-318. Epub 2019 Feb 12.

Department of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; San Francisco VA Medical Center, San Francisco, CA, USA.

Dysfunction in 24-h circadian rhythms is a common occurrence in ageing adults; however, circadian rhythm disruptions are more severe in people with age-related neurodegenerative diseases, including Alzheimer's disease and related dementias, and Parkinson's disease. Manifestations of circadian rhythm disruptions differ according to the type and severity of neurodegenerative disease and, for some patients, occur before the onset of typical clinical symptoms of neurodegeneration. Evidence from preliminary studies suggest that circadian rhythm disruptions, in addition to being a symptom of neurodegeneration, might also be a potential risk factor for developing Alzheimer's disease and related dementias, and Parkinson's disease, although large, longitudinal studies are needed to confirm this relationship. Read More

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http://dx.doi.org/10.1016/S1474-4422(18)30461-7DOI Listing

Memantine protects thalamocortical hyper-glutamatergic transmission induced by NMDA receptor antagonism via activation of system xc.

Pharmacol Res Perspect 2019 Feb;7(1):e00457

Department of Neuropsychiatry, Division of Neuroscience, Graduate School of Medicine, Mie University, Tsu, Mie, Japan.

Deficiencies in N-methyl-d-aspartate (NMDA)/glutamate receptor (NMDAR) signaling have been considered central to the cognitive impairments of schizophrenia; however, an NMDAR antagonist memantine (MEM) improves cognitive impairments of Alzheimer's disease and schizophrenia. These mechanisms of paradoxical clinical effects of NMDAR antagonists remain unclear. To explore the mechanisms by which MK801 and MEM affect thalamocortical transmission, we determined interactions between local administrations of MK801, MEM, system xc (Sxc), and metabotropic glutamate receptors (mGluRs) on extracellular glutamate and GABA levels in the mediodorsal thalamic nucleus (MDTN) and medial prefrontal cortex (mPFC) using dual-probe microdialysis with ultra-high-pressure liquid chromatography. Read More

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http://dx.doi.org/10.1002/prp2.457DOI Listing
February 2019

Metformin protects PC12 cells and hippocampal neurons from H O -induced oxidative damage through activation of AMPK pathway.

J Cell Physiol 2019 Feb 19. Epub 2019 Feb 19.

Center of Reproduction, Development & Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.

Metformin, a first line anti type 2 diabetes drug, has recently been shown to extend lifespan in various species, and therefore, became the first antiaging drug in clinical trial. Oxidative stress due to excess reactive oxygen species (ROS) is considered to be an important factor in aging and related disease, such as Alzheimer's disease (AD). However, the antioxidative effects of metformin and its underlying mechanisms in neuronal cells is not known. Read More

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http://dx.doi.org/10.1002/jcp.28337DOI Listing
February 2019

Lavandula angustifolia biological characteristics: An in vitro study.

J Cell Physiol 2019 Feb 19. Epub 2019 Feb 19.

Physiology Research Center, Kashan University of Medical Sciences, Kashan, I. R. Iran.

Objective: Lavender is an aromatic shrub belonging to the Lamiaceae family. The flowers and leaves in different forms of extracts are used as herbal medicine. The accumulation of amyloid beta (Aβ) plaques, reduction of acetylcholine due to hyperactivity of acetylcholinesterase, and glutamate neurotoxicity are known to be involved in decreased level of cognitive function. Read More

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http://dx.doi.org/10.1002/jcp.28311DOI Listing
February 2019

Correlations Between Single Nucleotide Polymorphisms, Cognitive Dysfunction, and Postmortem Brain Pathology in Alzheimer's Disease Among Han Chinese.

Neurosci Bull 2019 Feb 19. Epub 2019 Feb 19.

Institute of Basic Medical Sciences, Department of Human Anatomy, Histology and Embryology, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.

In this study, the distribution of five Alzheimer's disease (AD)-related single nucleotide polymorphisms (SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain pathological analysis. The associations among SNPs, clinical daily cognitive states, and postmortem neuropathological changes were analyzed in 110 human brains from the Chinese Academy of Medical Sciences/Peking Union Medical College (CAMS/PUMC) Human Brain Bank. APOE ε4 (OR = 4. Read More

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http://dx.doi.org/10.1007/s12264-019-00343-2DOI Listing
February 2019

Incidence of head injury and traumatic brain injury among people with Alzheimer's disease.

J Epidemiol Community Health 2019 Feb 19. Epub 2019 Feb 19.

School of Pharmacy, University of Eastern Finland, Kuopio, Finland.

Background: Injuries caused by falling are a major health concern among older population. For older people, falls are the leading cause of head injuries; especially, persons with cognitive disorders have an increased risk of falling.

Objective: To compare the incidence of head injury and traumatic brain injury (TBI) among persons with Alzheimer's disease (AD) with persons without AD. Read More

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http://dx.doi.org/10.1136/jech-2018-211960DOI Listing
February 2019

European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS): study protocol.

BMJ Open 2019 Feb 19;8(12):e021017. Epub 2019 Feb 19.

Centre for Dementia Prevention, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.

Introduction: The European Prevention of Alzheimer's Dementia (EPAD) project is funded initially by the Innovative Medicines Initiative and has been established to overcome the major hurdles hampering drug development for secondary prevention of Alzheimer's dementia, by conducting the EPAD Longitudinal Cohort Study (LCS) in alignment with the Bayesian adaptive designed EPAD Proof-of-Concept (PoC) trial.

Methods And Analysis: EPAD LCS is an ongoing prospective, multicentre, pan-European longitudinal cohort study. Participants are recruited mainly from existing parent cohorts across Europe to form a 'probability-spectrum' population covering the entire continuum of anticipated probability for Alzheimer's dementia development. Read More

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http://dx.doi.org/10.1136/bmjopen-2017-021017DOI Listing
February 2019

Hormonal modulation of cholesterol: experimental evidence and possible translational impact.

Expert Rev Endocrinol Metab 2012 May;7(3):309-318

a Department of Clinical Physiopathology, Endocrine Unit, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies (DENOThe), University of Florence, Florence, Italy.

Alzheimer's disease (AD) is still an incurable condition. There is in vitro evidence that estrogens exert neuroprotective effects; however, their role in the treatment of AD is still controversial. Approximately 10 years ago, a new gene, named seladin-1 (for selective AD indicator-1), was identified and found to be downregulated in brain regions affected by AD. Read More

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http://dx.doi.org/10.1586/eem.12.12DOI Listing

Sleep Disturbance as a Potential Modifiable Risk Factor for Alzheimer's Disease.

Int J Mol Sci 2019 Feb 13;20(4). Epub 2019 Feb 13.

Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira 187-8502, Japan.

Sleep disturbance is a common symptom in patients with various neurodegenerative diseases, including Alzheimer's disease (AD), and it can manifest in the early stages of the disease. Impaired sleep in patients with AD has been attributed to AD pathology that affects brain regions regulating the sleep⁻wake or circadian rhythm. However, recent epidemiological and experimental studies have demonstrated an association between impaired sleep and an increased risk of AD. Read More

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http://dx.doi.org/10.3390/ijms20040803DOI Listing
February 2019

DesMol2, an Effective Tool for the Construction of Molecular Libraries and Its Application to QSAR Using Molecular Topology.

Molecules 2019 Feb 18;24(4). Epub 2019 Feb 18.

Molecular Topology and Drug Design Unit, Department of Physical Chemistry, University of Valencia, Avenida V.A. Estelles s/n, Burjassot, 46100 Valencia, Spain.

A web application, DesMol2, which offers two main functionalities, is presented: the construction of molecular libraries and the calculation of topological indices. These functionalities are explained through a practical example of research of active molecules to the formylpeptide receptor (FPR), a receptor associated with chronic inflammation in systemic amyloidosis and Alzheimer's disease. Starting from a data(base) of 106 dioxopiperazine pyrrolidin piperazine derivatives and their respective constant values of binding affinity to FPR, multilinear regression and discriminant analyses are performed to calculate several predictive topological-mathematical models. Read More

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http://dx.doi.org/10.3390/molecules24040736DOI Listing
February 2019

Astaxanthin Ameliorates Lipopolysaccharide-Induced Neuroinflammation, Oxidative Stress and Memory Dysfunction through Inactivation of the Signal Transducer and Activator of Transcription 3 Pathway.

Mar Drugs 2019 Feb 18;17(2). Epub 2019 Feb 18.

Department of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Korea.

Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer's disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Read More

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http://dx.doi.org/10.3390/md17020123DOI Listing
February 2019

The Effectiveness of Vitamin E Treatment in Alzheimer's Disease.

Int J Mol Sci 2019 Feb 18;20(4). Epub 2019 Feb 18.

Department of Clinic Neurophysiology, University Clinic Hospital of Valencia, Avda. Blasco Ibanez, 19, 46010 Valencia, Spain.

Vitamin E was proposed as treatment for Alzheimer's disease many years ago. However, the effectiveness of the drug is not clear. Vitamin E is an antioxidant and neuroprotector and it has anti-inflammatory and hypocholesterolemic properties, driving to its importance for brain health. Read More

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http://dx.doi.org/10.3390/ijms20040879DOI Listing
February 2019
2.862 Impact Factor

Hippocampal Gene Expression is Increased in Late-Stage Alzheimer's Disease.

Int J Mol Sci 2019 Feb 18;20(4). Epub 2019 Feb 18.

Neuroepigenetics Laboratory-Navarrabiomed, Complejo Hospitalario de Navarra, Universidad Pública de Navarra (UPNA), IdiSNA (Navarra Institute for Health Research), Pamplona, Navarra 31008, Spain.

Lamins are fibrillary proteins that are crucial in maintaining nuclear shape and function. Recently, B-type lamin dysfunction has been linked to tauopathies. However, the role of A-type lamin in neurodegeneration is still obscure. Read More

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http://dx.doi.org/10.3390/ijms20040878DOI Listing
February 2019

Ingredients in Zijuan Pu'er Tea Extract Alleviate β-Amyloid Peptide Toxicity in a Model of Alzheimer's Disease Likely through DAF-16.

Molecules 2019 Feb 18;24(4). Epub 2019 Feb 18.

National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.

Amyloid-β, one of the hallmarks of Alzheimer's disease (AD), is toxic to neurons and can also cause brain cell death. Oxidative stress is known to play an important role in AD, and there is strong evidence that oxidative stress is associated with amyloid-β. In the present study we report the protective effect of Zijuan Pu'er tea water extract (ZTWE) and the mixture of main ingredients (+)-catechins, caffeine and procyanidin (MCCP) in ZTWE on β-amyloid-induced toxicity in transgenic () CL4176 expressing the human Aβ gene. Read More

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http://dx.doi.org/10.3390/molecules24040729DOI Listing
February 2019
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9-Methylfascaplysin Is a More Potent Aβ Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells.

Mar Drugs 2019 Feb 18;17(2). Epub 2019 Feb 18.

School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, China.

β-Amyloid (Aβ) is regarded as an important pathogenic target for Alzheimer's disease (AD), the most prevalent neurodegenerative disease. Aβ can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Aβ aggregation inhibitors may have anti-AD therapeutic efficacies. Read More

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http://dx.doi.org/10.3390/md17020121DOI Listing
February 2019

Molecular Docking Studies of Coumarins Isolated from Extracts and Essential Oils of Link as Potential Inhibitors for Alzheimer's Disease.

Molecules 2019 Feb 17;24(4). Epub 2019 Feb 17.

Department of Plant Physiology, Slovak Agricultural University in Nitra, 94976 Nitra, Slovak.

Coumarins and essential oils are the major components of the Apiaceae family and the genus. The present study reports anticholinesterase and antioxidant activities of extracts and essential oils from aerial parts, roots, flowers, fruits and coumarins-bergapten (); imperatorin (), pimpinellin () and umbelliferone ()-isolated of the roots from . The investigation by light and scanning electron microscopy of the structures of secretory canals found different chemical compositions in the various types of secretory canals which present in the aerial parts, fruits and flowers. Read More

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http://dx.doi.org/10.3390/molecules24040722DOI Listing
February 2019

Associations of insulin resistance with cognition in individuals without diagnosed diabetes: Results from the Hispanic Community Health Study/Study of Latinos.

Diabetes Res Clin Pract 2019 Feb 16. Epub 2019 Feb 16.

Institute for Minority Health Research, University of Illinois at Chicago, Chicago, IL; Department of Medicine, University of Illinois at Chicago, Chicago, IL; Rush Alzheimer's Disease Center and Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL. Electronic address:

Aims: Insulin resistance (IR) adversely impacts memory and executive functioning in non-Hispanic whites without diabetes. Less is known in Hispanics/Latinos, despite the fact that Hispanics/Latinos have higher rates of insulin resistance than non-Hispanic whites. We investigated the association between IR and cognition and its variation by age. Read More

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http://dx.doi.org/10.1016/j.diabres.2019.01.030DOI Listing
February 2019

Predicting cognitive resilience from midlife lifestyle and multi-modal MRI: A 30-year prospective cohort study.

PLoS One 2019 19;14(2):e0211273. Epub 2019 Feb 19.

Department of Psychiatry, University of Oxford, Oxford, United Kingdom.

Background: There is significant heterogeneity in the clinical expression of structural brain abnormalities, including Alzheimer's disease biomarkers. Some individuals preserve their memory despite the presence of risk factors or pathological brain changes, indicating resilience. We aimed to test whether resilient individuals could be distinguished from those who develop cognitive impairment, using sociodemographic variables and neuroimaging. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211273PLOS
February 2019

Potential role of miRNA-140 in Alzheimer's disease.

Aging (Albany NY) 2019 Feb 19. Epub 2019 Feb 19.

Cleveland Clinic Lerner Research Institute, Cleveland, OH 44106, USA.

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http://dx.doi.org/10.18632/aging.101827DOI Listing
February 2019

Iso-α-acids, Hop-Derived Bitter Components of Beer, Attenuate Age-Related Inflammation and Cognitive Decline.

Front Aging Neurosci 2019 4;11:16. Epub 2019 Feb 4.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

With the aging population rapidly increasing worldwide, preventive measures and treatments for age-related cognitive decline and dementia are of utmost importance. We have previously demonstrated that the consumption of iso-α-acids (IAA), which are hop-derived bitter compounds in beer, prevents the formation of disease pathology in a transgenic mouse model of Alzheimer's disease (AD). However, the effect of IAA consumption on age-related cognitive decline is unknown. Read More

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http://dx.doi.org/10.3389/fnagi.2019.00016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369178PMC
February 2019

Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology.

Mol Psychiatry 2019 Feb 18. Epub 2019 Feb 18.

Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Vic, Australia.

Cortical iron has been shown to be elevated in Alzheimer's disease (AD), but the impact of the directly measured iron on the clinical syndrome has not been assessed. We investigated the association between post-mortem iron levels with the clinical and pathological diagnosis of AD, its severity, and the rate of cognitive decline in the 12 years prior to death in subjects from the Memory and Aging Project (n = 209). Iron was elevated (β [SE] = 9. Read More

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http://dx.doi.org/10.1038/s41380-019-0375-7DOI Listing
February 2019

Beyond episodic memory: Semantic processing as independent predictor of hippocampal/perirhinal volume in aging and mild cognitive impairment due to Alzheimer's disease.

Neuropsychology 2019 Feb 18. Epub 2019 Feb 18.

Department of Neuroscience, University of Sheffield.

Objective: Given that lexical-semantic decline precedes episodic memory deficits in the Alzheimer's disease (AD) timeline, it is expected that performance on a lexical-semantic task would be associated with mediotemporal volumes independently of the association this region has with episodic memory in the early stage of AD.

Method: Fifty patients with mild cognitive impairment due to AD and 50 healthy adults completed tests of lexical-semantic skills (category fluency test), episodic memory for semantically relevant material (prose memory test), episodic memory for non semantically relevant material (Rey-Osterrieth Figure test), lexical-executive abilities (letter fluency test), and a neurostructural MRI. Hippocampal, perirhinal, entorhinal, temporopolar, and orbitofrontal volumes were extracted. Read More

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http://dx.doi.org/10.1037/neu0000534DOI Listing
February 2019

Impaired behavioural flexibility related to white matter microgliosis in the TgAPP21 rat model of Alzheimer disease.

Brain Behav Immun 2019 Feb 15. Epub 2019 Feb 15.

Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, Western University, London ON, Canada; Department of Clinical Neurological Sciences, University Hospital, Western University, London, ON, Canada. Electronic address:

Executive dysfunction and white matter inflammation continue to be relatively understudied in rodent models of Alzheimer's disease (AD). Behavioural inflexibility is an important component of executive dysfunction that can be further categorized as perseverative or regressive, which respectively specify whether maladaptive persistence occurs early or late during a behavioural change. Previous studies of the TgAPP21 rat model of AD (expressing pathogenic hAPP) suggested a potentially spontaneous increase of regressive behavioral inflexibility. Read More

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http://dx.doi.org/10.1016/j.bbi.2019.02.013DOI Listing
February 2019

Microglia - mediated immunity partly contributes to the genetic association between Alzheimer's disease and hippocampal volume.

Brain Behav Immun 2019 Feb 15. Epub 2019 Feb 15.

UK Dementia Research Institute, School of Medicine, Cardiff University, United Kingdom; MRC Centre of Neuropsychiatric Genetics & Genomics, School of Medicine, Cardiff University, United Kingdom.

Genome-wide association studies (GWAS) suggest that Alzheimer's disease (AD) is partly explained by a burden of risk alleles (single nucleotide polymorphisms; SNPs) with relatively small effects. However, the mechanisms by which these loci cumulatively confer susceptibility remain largely unknown. Accumulating evidence suggests an association between increased AD risk allele burden (measured via a polygenic risk profile score; AD-RPS) with reduced hippocampal volume (HV) across a number of independent cohorts. Read More

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

Telomere length and health outcomes: An umbrella review of systematic reviews and meta-analyses of observational studies.

Ageing Res Rev 2019 Feb 15;51:1-10. Epub 2019 Feb 15.

National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy. Electronic address:

The aim of the present study was to map and grade evidence for the relationships between telomere length with a diverse range of health outcomes, using an umbrella review of systematic reviews with meta-analyses. We searched for meta-analyses of observational studies reporting on the association of telomere length with any health outcome (clinical disease outcomes and intermediate traits). For each association, random-effects summary effect size, 95% confidence interval (CI), and 95% prediction interval were calculated. Read More

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http://dx.doi.org/10.1016/j.arr.2019.02.003DOI Listing
February 2019
1 Read
4.940 Impact Factor

Treatment of Alzheimer's Disease: Trazodone, Sleep, Serotonin, Norepinephrine, and Future Directions.

J Alzheimers Dis 2019 ;67(3):923-930

War Related Illness and Injury Study Center, VA Palo Alto Health Care System and Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA.

In this issue, an article by La et al. provides evidence that trazodone delayed cognitive decline in 25 participants with Alzheimer's disease (AD), mild cognitive impairment, or normal cognition. For participants considered to have AD pathology, trazodone non-users declined at a rate 2. Read More

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http://dx.doi.org/10.3233/JAD-181106DOI Listing
January 2019
1 Read

Is Alzheimer's Disease Risk Modifiable?

J Alzheimers Dis 2019 ;67(3):795-819

Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.

Population-based clinic-pathological studies have established that the most common pathological substrate of dementia in community-dwelling elderly people is mixed, especially Alzheimer's disease (AD) and cerebrovascular ischemic disease (CVID), rather than pure AD. While these could be just two frequent unrelated comorbidities in the elderly, epidemiological research has reinforced the idea that mid-life (age <65 years) vascular risk factors increase the risk of late-onset (age ≥ 65 years) dementia, and specifically AD. By contrast, healthy lifestyle choices such as leisure activities, physical exercise, and Mediterranean diet are considered protective against AD. Read More

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http://dx.doi.org/10.3233/JAD181028DOI Listing
January 2019

The MemTrax Test Compared to the Montreal Cognitive Assessment Estimation of Mild Cognitive Impairment.

J Alzheimers Dis 2019 ;67(3):1045-1054

War Related Illness and Injury Study Center, VA Palo Alto HCS, Palo Alto, CA, USA.

Cognitive impairment is a leading cause of dysfunction in the elderly. When mild cognitive impairment (MCI) occurs in elderly, it is frequently a prodromal condition to dementia. The Montreal Cognitive Assessment (MoCA) is a commonly used tool to screen for MCI. Read More

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http://dx.doi.org/10.3233/JAD-181003DOI Listing
January 2019

Small Molecule Amyloid-β Protein Precursor Processing Modulators Lower Amyloid-β Peptide Levels via cKit Signaling.

J Alzheimers Dis 2019 ;67(3):1089-1106

Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.

Alzheimer's disease (AD) is characterized by the accumulation of neurotoxic amyloid-β (Aβ) peptides consisting of 39-43 amino acids, proteolytically derived fragments of the amyloid-β protein precursor (AβPP), and the accumulation of the hyperphosphorylated microtubule-associated protein tau. Inhibiting Aβ production may reduce neurodegeneration and cognitive dysfunction associated with AD. We have previously used an AβPP-firefly luciferase enzyme complementation assay to conduct a high throughput screen of a compound library for inhibitors of AβPP dimerization, and identified a compound that reduces Aβ levels. Read More

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http://dx.doi.org/10.3233/JAD-180923DOI Listing
January 2019

Resistance Exercise-Induced Responses in Physiological Factors Linked with Cognitive Health.

J Alzheimers Dis 2019 Feb 13. Epub 2019 Feb 13.

School of Psychology and Exercise Science, Murdoch University, Perth, Western Australia, Australia.

The global population is aging at an unprecedented rate giving rise to a greater prevalence of age-related illnesses such as dementia and vascular disease. Dementia affects approximately 47 million individuals globally with projections of 130 million by the year 2050. Late-onset Alzheimer's disease is the most common form of dementia, accounting for approximately 75% of all cases and is characterized by a progressive decline in cognitive function, memory, and cerebral volume. Read More

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http://dx.doi.org/10.3233/JAD-181079DOI Listing
February 2019

Cognitive Improvement with Glutathione Supplement in Alzheimer's Disease: A Way Forward.

J Alzheimers Dis 2019 Feb 13. Epub 2019 Feb 13.

Department of Clinical Engineering, Haukeland University Hospital, Bergen, Norway.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting millions of people worldwide. The actual cause of AD is still unknown. Oxidative stress is believed to be important player in AD. Read More

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http://dx.doi.org/10.3233/JAD-181054DOI Listing
February 2019

Identification of Key Long Non-Coding RNAs in the Pathology of Alzheimer's Disease and their Functions Based on Genome-Wide Associations Study, Microarray, and RNA-seq Data.

J Alzheimers Dis 2019 Feb 13. Epub 2019 Feb 13.

Innovative Drug Research and Bioinformatics Group, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

The pathogenesis of Alzheimer's disease (AD) is identified to be significantly regulated by long non-coding RNA (lncRNA) based on in vivo and clinical experiments. Single nucleotide polymorphisms (SNPs) can strongly impact expression and function of lncRNA in AD, and previous genome-wide associations studies (GWAS) have discovered substantial amount of risk SNPs associated with AD. However, current studies omit the important information about SNPs when identifying potential AD-related lncRNAs. Read More

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http://dx.doi.org/10.3233/JAD-181051DOI Listing
February 2019

Head-to-Head Comparison among Semi-Quantification Tools of Brain FDG-PET to Aid the Diagnosis of Prodromal Alzheimer's Disease.

J Alzheimers Dis 2019 Feb 13. Epub 2019 Feb 13.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child health (DINOGMI), University of Genoa, Italy.

Background: Several automatic tools have been implemented for semi-quantitative assessment of brain [18]F-FDG-PET.

Objective: We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e. Read More

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http://dx.doi.org/10.3233/JAD-181022DOI Listing
February 2019
1 Read

FTIR Spectroscopy of Cerebrospinal Fluid Reveals Variations in the Lipid: Protein Ratio at Different Stages of Alzheimer's Disease.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

Faculty of Mathematics and Natural Sciences, Centre for Innovation and Transfer of Natural Sciences and Engineering Knowledge, University of Rzeszow, Poland.

Alzheimer's disease (AD) is a disease of advanced civilization and a common form of dementia in people over 65 years of age. We used Fourier transform infrared (FTIR) spectroscopy combined with principal component analysis (PCA) to determine changes in the quantity and quality of the cerebrospinal fluid from AD patients at three different stages of the disease (ADI, ADII, and ADIII), as well as from patients with mild cognitive impairment (MCI). Moreover, based on the FTIR spectra, we calculated the ratio of α-helix and β-sheet secondary protein structures as well as the lipid-protein balance as potential AD markers. Read More

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http://dx.doi.org/10.3233/JAD-181008DOI Listing
February 2019
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A Potential Role for α-Amylase in Amyloid-β-Induced Astrocytic Glycogenolysis and Activation.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Malmö, Sweden.

Background: Astrocytes produce and store the energy reserve glycogen. However, abnormal large glycogen units accumulate if the production or degradation of glycogen is disturbed, a finding often seen in patients with Alzheimer's disease (AD). We have shown increased activity of glycogen degrading α-amylase in AD patients and α-amylase positive glial cells adjacent to AD characteristic amyloid-β (Aβ) plaques. Read More

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http://dx.doi.org/10.3233/JAD-180997DOI Listing
February 2019

White Matter Hyperintensities in Alzheimer's Disease: A Lesion Probability Mapping Study.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

Department of Neurology, Medical University of Graz, Graz, Austria.

Background/objective: Higher white matter hyperintensity (WMH) load has been reported in Alzheimer's disease (AD) patients in different brain regions when compared to controls. We aimed to assess possible differences of WMH spatial distribution between AD patients and age-matched controls by means of lesion probability maps.

Methods: The present study included MRI scans of 130 probable AD patients with a mean age of 73. Read More

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http://dx.doi.org/10.3233/JAD-180982DOI Listing
February 2019
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The Influence of BDNF Val66Met Polymorphism on Cognition, Cerebrospinal Fluid, and Neuroimaging Markers in Non-Demented Elderly.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Background: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism emerged as a risk factor for Alzheimer's disease (AD). However, little was known about its effects on the process of potential AD.

Objective: To explore the effects of the Val66Met polymorphism on cognition, cerebrospinal fluid (CSF), and neuroimaging markers in non-demented elderly individuals. Read More

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http://dx.doi.org/10.3233/JAD-180971DOI Listing
February 2019
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Vascular Burden Score Impacts Cognition Independent of Amyloid PET and MRI Measures of Alzheimer's Disease and Vascular Brain Injury.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

UC Davis Department of Neurology and Center for Neuroscience, Davis, CA, USA.

Background/objective: To determine the impact of vascular burden on rates of decline in episodic memory and executive function. We hypothesize that greater vascular burden will have an additive negative impact on cognition after accounting for baseline cognitive impairment, positron emission tomography (PET) amyloid burden, and magnetic resonance imaging (MRI) measures.

Methods: Individuals were followed an average of 5 years with serial cognitive assessments. Read More

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http://dx.doi.org/10.3233/JAD-180965DOI Listing
February 2019

Antiepileptic Drug Use Is Associated with an Increased Risk of Pneumonia Among Community-Dwelling Persons with Alzheimer's Disease-Matched Cohort Study.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

School of Pharmacy, University of Eastern Finland, Kuopio, Finland.

Background: Antiepileptic drugs (AEDs) have sedative properties which may lead to an increased risk of pneumonia.

Objectives: To investigate whether incident AED use is associated with an increased risk of pneumonia among community-dwelling persons with Alzheimer's disease (AD). In addition, we determined the risk according to duration of AED use and specific AEDs. Read More

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http://dx.doi.org/10.3233/JAD-180912DOI Listing
February 2019
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Identification of a Simple and Novel Cut-Point Based Cerebrospinal Fluid and MRI Signature for Predicting Alzheimer's Disease Progression that Reinforces the 2018 NIA-AA Research Framework.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Champaign, IL, USA.

The 2018 NIA-AA research framework proposes a classification system with Amyloid-β deposition, pathologic Tau, and neurodegeneration (ATN) for diagnosis and staging of Alzheimer's disease (AD). Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database can be utilized to identify diagnostic signatures for predicting AD progression, and to determine the utility of this NIA-AA research framework. Profiles of 320 peptides from baseline cerebrospinal fluid (CSF) samples of 287 normal, mild cognitive impairment (MCI), and AD subjects followed over a 3-10-year period were measured via multiple reaction monitoring mass spectrometry. Read More

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http://dx.doi.org/10.3233/JAD-180905DOI Listing
February 2019

Distinctive Neurochemistry in Alzheimer's Disease via 7 T In Vivo Magnetic Resonance Spectroscopy.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN, USA.

This study's objective was to increase understanding of biological mechanisms underlying clinical Alzheimer's disease (AD) by noninvasively measuring an expanded neurochemical profile and exploring how well this advanced technology distinguishes AD from cognitively normal controls. We measured concentrations of 14 neurochemicals using ultra-high field (7 T) ultra-short echo time (8 ms) magnetic resonance spectroscopy (MRS) in 16 participants with mild to moderate clinical AD and 33 age- and gender-matched control participants. MRS was localized to the posterior cingulate cortex (PCC), a region known to be impacted by AD, and the occipital cortex (OCC), a control region. Read More

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http://dx.doi.org/10.3233/JAD-180861DOI Listing
February 2019
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Impaired Glucose Tolerance and Reduced Plasma Insulin Precede Decreased AKT Phosphorylation and GLUT3 Translocation in the Hippocampus of Old 3xTg-AD Mice.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, USA.

Several studies have demonstrated that mouse models of Alzheimer's disease (AD) can exhibit impaired peripheral glucose tolerance. Further, in the APP/PS1 mouse model, this is observed prior to the appearance of AD-related neuropathology (e.g. Read More

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http://dx.doi.org/10.3233/JAD-180707DOI Listing
February 2019

The Alz-tau Biomarker for Alzheimer's Disease: Study in a Caucasian Population.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

Laboratory of Neuroscience, International Center for Biomedicine (ICC) and Faculty of Sciences, University of Chile, Santiago, Chile.

The establishment of a molecular biomarker for early detection of Alzheimer's disease (AD) is critical for diagnosis and follow up of patients, and as a quantitative parameter in the evaluation of potential new drugs to control AD. A list of blood biomarkers has been reported but none has been validated for the Alzheimer's clinic. The changes in hyperphosphorylated tau and amyloid peptide in the cerebrospinal fluid is currently used as a tool in the clinics and for research purposes, but this method is highly invasive. Read More

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http://dx.doi.org/10.3233/JAD-180637DOI Listing
February 2019

Serum Potassium Is Associated with Cognitive Decline in Patients with Lewy Body Dementia.

J Alzheimers Dis 2019 Feb 9. Epub 2019 Feb 9.

Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.

Background: Epidemiological studies link serum potassium (K +) to cognitive performance, but whether cognitive prognosis in dementia is related to K + levels is unknown.

Objective: To determine if K + levels predict cognitive prognosis in dementia and if this varies according to diagnosis or neuropathological findings.

Methods: This longitudinal cohort study recruited 183 patients with mild Alzheimer's disease or Lewy body dementia (LBD). Read More

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http://dx.doi.org/10.3233/JAD-181131DOI Listing
February 2019

On the Etiopathogenesis and Pathophysiology of Alzheimer's Disease: A Comprehensive Theoretical Review.

J Alzheimers Dis 2019 Feb 8. Epub 2019 Feb 8.

Johns Hopkins University.

Alzheimers' disease (AD) is the most common cause of dementia, with an estimated 5 million new cases occurring annually. Among the elderly, AD shortens life expectancy, results in disability, decreases quality of life, and ultimately, leads to institutionalization. Despite extensive research in the last few decades, its heterogeneous pathophysiology and etiopathogenesis have made it difficult to develop an effective treatment and prevention strategy. Read More

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http://dx.doi.org/10.3233/JAD-181052DOI Listing
February 2019

The role of mitochondrial defects and oxidative stress in Alzheimer's disease.

J Drug Target 2019 Feb 18:1-32. Epub 2019 Feb 18.

b King Fahd Medical Research Center, King Abdulaziz University , Jeddah , 21589 , Saudi Arabia.

Alzheimer's disease (AD) is a complex, progressive, irreversible neurodegenerative disorder. Recent reports suggest that it affects more than 36 million people worldwide and accounts 60-80% of all cases of dementia. It is characterized by aberrations of multiple interactive systems and pathways, which ultimately lead to memory loss and cognitive dysfunction. Read More

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http://dx.doi.org/10.1080/1061186X.2019.1584808DOI Listing
February 2019