101,963 results match your criteria Alzheimer Disease


Tau PET Imaging for Staging of Alzheimer's Disease in Down Syndrome.

Authors:
Michael S Rafii

Dev Neurobiol 2018 Dec 8. Epub 2018 Dec 8.

Alzheimer's Therapeutic Research Institute (ATRI), Keck School of Medicine, University of Southern California.

Alzheimer's disease (AD) pathology and early-onset dementia develop almost universally in Down syndrome (DS). AD is defined neuropathologically by the presence of extracellular plaques of aggregated amyloid β protein and intracellular neurofibrillary tangles (NFTs) of aggregated hyperphosphorylated tau protein. The development of radiolabeled positron emission tomography (PET) ligands for amyloid plaques and tau tangles enables the longitudinal assessment of the spatial pattern of their accumulation in relation to symptomatology. Read More

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December 2018
1 Read

The Fyn kinase inhibitor, AZD0530, suppresses mouse alcohol self-administration and seeking.

Addict Biol 2018 Dec 7. Epub 2018 Dec 7.

Department of Neurology, University of California San Francisco, San Francisco, California.

Fyn is a member of the Src family of protein tyrosine kinases (PTKs) that plays an important role not only in normal synaptic functions but also in brain pathologies including alcohol use disorder. We previously reported that repeated cycles of binge drinking and withdrawal activate Fyn in the dorsomedial striatum (DMS) of rodents, and that Fyn signaling in the DMS contributes to rat alcohol intake and relapse. Here, we used AZD0530, a CNS penetrable inhibitor of Src PTKs developed for the treatment of Alzheimer disease and cancer and tested its efficacy to suppress alcohol-dependent molecular and behavioral effects. Read More

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December 2018

Evaluation of salivary acetylcholinesterase and pseudocholinesterase in patients with Alzheimer's disease: A case-control study.

Spec Care Dentist 2018 Dec 11. Epub 2018 Dec 11.

Assistant Professor of Linguistics, Department of Persian Literature and English Language, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Aim: The aim of this study was to evaluate acetylcholinesterase (AChE) and pseudocholinesterase (PChE) in whole saliva in patients with Alzheimer's disease (AD) and in healthy subjects. Saliva has a high potential for keeping track of general health and diseases. AD is a type of dementia with reduction in brain cholinergic markers that causes memory, thinking, and behavior problems. Read More

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December 2018

Where do white matter alterations dovetail with the cascade model of Alzheimer's disease?

Brain 2018 Oct;141(10):2830-2833

The Florey Institute and Melbourne School of Psychological Science, The University of Melbourne, Victoria, Australia.

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October 2018

Neuro-Immune Hemostasis: Homeostasis and Diseases in the Central Nervous System.

Front Cell Neurosci 2018 26;12:459. Epub 2018 Nov 26.

Laboratory of Morphology of Neuronal Network, Department of Public Medicine, University of Campania-Luigi Vanvitelli, Naples, Italy.

Coagulation and the immune system interact in several physiological and pathological conditions, including tissue repair, host defense, and homeostatic maintenance. This network plays a key role in diseases of the central nervous system (CNS) by involving several cells (CNS resident cells, platelets, endothelium, and leukocytes) and molecular pathways (protease activity, complement factors, platelet granule content). Endothelial damage prompts platelet activation and the coagulation cascade as the first physiological step to support the rescue of damaged tissues, a flawed rescuing system ultimately producing neuroinflammation. Read More

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November 2018
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Natriuretic Peptides in Post-mortem Brain Tissue and Cerebrospinal Fluid of Non-demented Humans and Alzheimer's Disease Patients.

Front Neurosci 2018 26;12:864. Epub 2018 Nov 26.

Department of Radiology, Leiden University Medical Center, Leiden, Netherlands.

Animal studies suggest the involvement of natriuretic peptides (NP) in several brain functions that are known to be disturbed during Alzheimer's disease (AD). However, it remains unclear whether such findings extend to humans. In this study, we aimed to: (1) map the gene expression and localization of NP and their receptors (NPR) in human post-mortem brain tissue; (2) compare the relative amounts of NP and NPR between the brain tissue of AD patients and non-demented controls, and (3) compare the relative amounts of NP between the cerebrospinal fluid (CSF) of AD patients and non-demented controls. Read More

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November 2018

Brain SIRT1 Mediates Metabolic Homeostasis and Neuroprotection.

Front Endocrinol (Lausanne) 2018 23;9:702. Epub 2018 Nov 23.

Cerebral Vascular Disease Research Laboratories, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, United States.

Sirtuins are evolutionarily conserved proteins that use nicotinamide adenine dinucleotide (NAD) as a co-substrate in their enzymatic reactions. There are seven proteins (SIRT1-7) in the human sirtuin family, among which SIRT1 is the most conserved and characterized. SIRT1 in the brain, in particular, within the hypothalamus, plays crucial roles in regulating systemic energy homeostasis and circadian rhythm. Read More

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November 2018

Ginkgolide C reduced oleic acid-induced lipid accumulation in HepG2 cells.

Saudi Pharm J 2018 Dec 20;26(8):1178-1184. Epub 2018 Jul 20.

Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Guishan Dist., Taoyuan City 33303, Taiwan.

Ginkgolide C, isolated from , is a diterpene lactone that has multiple biological functions and can improve Alzheimer disease and platelet aggregation. Ginkgolide C also inhibits adipogenesis in 3T3-L1 adipocytes. The present study evaluated whether ginkgolide C reduced lipid accumulation and regulated the molecular mechanism of lipogenesis in oleic acid-induced HepG2 hepatocytes. Read More

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December 2018

Olfactory and other sensory impairments in Alzheimer disease.

Authors:
Claire Murphy

Nat Rev Neurol 2018 Dec 10. Epub 2018 Dec 10.

Department of Psychology, San Diego State University, San Diego, CA, USA.

The vast increase in Alzheimer disease (AD) worldwide has grave implications for individuals, family support systems and the health-care systems that will attempt to cope with the disease. Early markers of the disease are essential for efficient selection of clinical trial participants for drug development and for timely treatment once an intervention becomes available. There is avid interest in noninvasive, inexpensive markers that have the potential to identify prodromal AD. Read More

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December 2018

Reduced Awareness of Memory Deficit is Associated With Increased Medicare Home Health Care Use in Dementia.

Alzheimer Dis Assoc Disord 2018 Dec 6. Epub 2018 Dec 6.

Cognitive Neuroscience Division of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the G.H. Sergievsky Center, Columbia University Medical Center.

Objective: The objective of this study was to examine whether reduced awareness of memory deficits in individuals with dementia is associated with more frequent need for Medicare home health care services.

Methods: Cross-sectional analyses were conducted in a multicenter, clinic-based cohort. In total, 192 participants diagnosed with dementia and their informants were independently asked whether or not the participant demonstrated cognitive symptoms of dementia related to memory and word-finding. Read More

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December 2018

Decline in handgrip strength from midlife to late-life is associated with dementia in a Japanese community: the Hisayama Study.

J Epidemiol 2018 Dec 8. Epub 2018 Dec 8.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University.

Background: The association between decline in handgrip strength from midlife to late-life and dementia is unclear.

Methods: Japanese community-dwellers without dementia aged 60 to 79 (i.e. Read More

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December 2018

An innovative approach for the treatment of Alzheimer's disease: the role of peroxisome proliferator-activated receptors and their ligands in development of alternative therapeutic interventions.

Authors:
Luca Piemontese

Neural Regen Res 2019 Jan;14(1):43-45

Dipartimento Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Bari, Italy.

Alzheimer's disease is a multifactorial pathology, for which no cure is currently available. Nowadays, researchers are moving towards a new hypothesis of the onset of the illness, linking it to a metabolic impairment. This innovative approach will lead to the identification of new targets for the preparation of new effective drugs. Read More

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January 2019

MicroRNAs as diagnostic and therapeutic tools for Alzheimer's disease: advances and limitations.

Neural Regen Res 2019 Feb;14(2):242-255

Department of Anatomy, University of Otago, Dunedin, New Zealand.

Alzheimer's disease (AD) is the most common age-related, progressive neurodegenerative disease. It is characterized by memory loss and cognitive decline and responsible for most cases of dementia in the elderly. Late-onset or sporadic AD accounts for > 95% of cases, with age at onset > 65 years. Read More

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February 2019

Next Generation Sequencing Analysis in Early Onset Dementia Patients.

J Alzheimers Dis 2018 Dec 3. Epub 2018 Dec 3.

Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Background: Early onset dementias (EOD) are rare neurodegenerative dementias that present before 65 years. Genetic factors have a substantially higher pathogenetic contribution in EOD patients than in late onset dementia.

Objective: To identify known and/or novel rare variants in major candidate genes associated to EOD by high-throughput sequencing. Read More

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December 2018

Quantitative Analysis of F-PF-06684511, a Novel PET Radioligand for Selective β-secretase 1 Imaging, in Non-human Primate Brain.

J Nucl Med 2018 Dec 7. Epub 2018 Dec 7.

Karolinska Institutet, Sweden.

Beta-secretase 1 (BACE1) is a key enzyme in the generation of beta-amyloid, which is accumulated in the brain of Alzheimer's disease (AD) patients. PF-06684511 was identified as a candidate PET ligand for imaging BACE1 in the brain, and showed high specific binding in an initial assessment in a non-human primate (NHP) PET study utilizing F-PF-06684511. In this effort, we aimed to quantitatively evaluate the regional brain distribution of F-PF-06684511 in NHPs under baseline and blocking conditions as well as assess the target occupancy of BACE1 inhibitors. Read More

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December 2018

Translating the biology of aging into novel therapeutics for Alzheimer disease.

Neurology 2018 Dec 7. Epub 2018 Dec 7.

From the Alzheimer's Drug Discovery Foundation, New York, NY.

Aging is the leading risk factor for most chronic illnesses of old age, including Alzheimer disease (AD), a progressive neurodegenerative disease with currently no therapies that prevent, slow, or halt disease progression. Like other chronic diseases of old age, the progressive pathology of AD begins decades before the onset of symptoms. Many decades of research in biological gerontology have revealed common processes that are relevant to understanding why the aging brain is vulnerable to AD. Read More

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December 2018

Dietary lysophosphatidylcholine-EPA enriches both EPA and DHA in the brain: Potential treatment for depression.

J Lipid Res 2018 Dec 10. Epub 2018 Dec 10.

University of Illinois at Chicago, United States;

EPA and DHA protect against multiple metabolic and neurologic disorders. Although DHA appears more effective for neuroinflammatory conditions, EPA is more beneficial for depression. However, the brain contains negligible amounts of EPA, and dietary supplements fail to increase it appreciably. Read More

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December 2018

Polycyclic maleimide-based derivatives as first dual modulators of neuronal calcium channels and GSK-3β for Alzheimer's disease treatment.

Eur J Med Chem 2018 Dec 3;163:394-402. Epub 2018 Dec 3.

Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy. Electronic address:

Current healthcare has significantly increased the average life expectancy, leading to a consequently greater incidence of age-related diseases, such as Alzheimer's disease. Following a multitarget approach, in this paper a series of polycyclic maleimide-based derivatives were designed and synthesized aimed at simultaneously modulate neuronal calcium channels and glycogen synthase kinase 3-beta (GSK-3β), validated targets to combat Alzheimer' disease. Different structural modifications were performed on the polycyclic scaffold in order to investigate the structure-activity relationships and compound 10 emerged as a promising non-toxic lead compound, endowed with calcium modulating brain-addressed properties and significant GSK-3β inhibitory activity. Read More

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December 2018

Effect of apolipoprotein E4 on clinical, neuroimaging, and biomarker measures in noncarrier participants in the Dominantly Inherited Alzheimer Network.

Neurobiol Aging 2018 Oct 13;75:42-50. Epub 2018 Oct 13.

Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO; Department of Neurology, Washington University School of Medicine, Saint Louis, MO.

The apolipoprotein E ε4 allele (APOE4) is the major genetic risk factor for sporadic Alzheimer's disease (AD). APOE4 may have effects on cognition and brain atrophy years before the onset of symptomatic AD. We analyzed the effects of APOE4 in a unique cohort of young adults who had undergone comprehensive assessments as part of the Dominantly Inherited Alzheimer Network (DIAN), an international longitudinal study of individuals from families with autosomal dominant AD. Read More

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October 2018

In-vitro evaluation studies of 7-chloro-4-aminoquinoline Schiff bases and their copper complexes as cholinesterase inhibitors.

J Inorg Biochem 2018 Nov 30;191:183-193. Epub 2018 Nov 30.

Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, 24020-141 Niterói, RJ, Brazil. Electronic address:

Alzheimer's disease (AD) is one of the most common age-related neurodegenerative disorders. Aggregation of amyloid-β peptide into extracellular plaques with incorporation of metal ions, such as Cu, and reduction of the neurotransmitter acetylcholine levels are among the factors associated to the AD brain. Hence, a series of 7-chloro-4-aminoquinoline Schiff bases (HLa-e) were synthesized and their cytotoxicity and anti-cholinesterase activity, assessed for Alzheimer's disease. Read More

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November 2018

Multi-target inhibitors against Alzheimer disease derived from 3-hydrazinyl 1,2,4-triazine scaffold containing pendant phenoxy methyl-1,2,3-triazole: Design, synthesis and biological evaluation.

Bioorg Chem 2018 Nov 29;84:363-371. Epub 2018 Nov 29.

Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Alzheimer's disease (AD) is a complex neurological disorder with diverse underlying pathological processes. Several lines of evidence suggest that BACE1 is a key enzyme in the pathogenesis of AD and its inhibition is of particular importance in AD treatment. Ten new 3-hydrazinyl-1,2,4-triazines bearing pendant aryl phenoxy methyl-1,2,3-triazole were synthesized as multifunctional ligands against AD. Read More

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November 2018

Synthesis and evaluation of isoprenylation-resveratrol dimer derivatives against Alzheimer's disease.

Eur J Med Chem 2018 Nov 26;163:307-319. Epub 2018 Nov 26.

Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. Biological analysis revealed that these derivatives had moderate inhibitory activity against human monoamine oxidase B (hMAO-B). In particular, 3 and 7 showed the better inhibitory activity for hMAO-B (IC = 3. Read More

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November 2018
3.447 Impact Factor

Spatiotemporal analysis for detection of pre-symptomatic shape changes in neurodegenerative diseases: Initial application to the GENFI cohort.

Neuroimage 2018 Dec 6. Epub 2018 Dec 6.

Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom; Dementia Research Centre, Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom.

Brain atrophy as measured from structural MR images, is one of the primary imaging biomarkers used to track neurodegenerative disease progression. In diseases such as frontotemporal dementia or Alzheimer's disease, atrophy can be observed in key brain structures years before any clinical symptoms are present. Atrophy is most commonly captured as volume change of key structures and the shape changes of these structures are typically not analysed despite being potentially more sensitive than summary volume statistics over the entire structure. Read More

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December 2018

Exercise and probiotics attenuate the development of Alzheimer's disease in transgenic mice: Role of microbiome.

Exp Gerontol 2018 Dec 6. Epub 2018 Dec 6.

Research Institute of Sport Science, University of Physical Education, Budapest, Hungary; Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, Japan. Electronic address:

It has been suggested that exercise training and probiotic supplementation could decelerate the progress of functional and biochemical deterioration in APP/PS1 transgenic mice (APP/PS1). APP/PS1 mice were subjected to exercise training and probiotic treatments and functional, biochemical and microbiome markers were analyzed. Under these conditions the mice significantly outperformed controls on The Morris Maze Test, and the number of beta-amyloid plaques decreased in the hippocampus. Read More

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December 2018

Intrinsic connectivity networks in posterior cortical atrophy: A role for the pulvinar?

Neuroimage Clin 2018 Dec 3. Epub 2018 Dec 3.

Memory and Aging Center, University of California, 675 Nelson Rising Lane, San Francisco, CA 94143, USA. Electronic address:

Background: Posterior cortical atrophy (PCA) is a clinical variant of Alzheimer's disease (AD) that presents with progressive visuospatial symptoms. While amnestic AD is characterized by disrupted default mode network (DMN) connectivity with corresponding increases in salience network (SN) connectivity, a visuospatial network appears to be disrupted early in PCA. Based on PCA patients' clinical features, we hypothesized that, in addition to early decreased integrity within the visuospatial network, patients with PCA would show increases in SN connectivity despite relative preservation of DMN. Read More

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December 2018

Gastroprotective effect of memantine in indomethacin-induced peptic ulcer in rats, a possible role for potassium channels.

Life Sci 2018 Dec 6. Epub 2018 Dec 6.

Department of Biochemistry, Faculty of Medicine, Minia University, Egypt.

Aims: Memantine is a commonly used drug in treating Alzheimer disease. In the current work, we aimed to evaluate the gastro-protective effect of memantine in indomethacin-induced peptic ulcer in rats.

Main Methods: Peptic ulcer induced by indomethacin and memantine administered either alone or in combination with glibenclamide or nitric oxide synthase (NOS) inhibitor. Read More

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December 2018

Activity-Induced Amyloid-β Oligomers Drive Compensatory Synaptic Rearrangements in Brain Circuits Controlling Memory of Presymptomatic Alzheimer's Disease Mice.

Biol Psychiatry 2018 Nov 2. Epub 2018 Nov 2.

Institute of Cell Biology and Neurobiology, National Research Council, Rome, Italy. Electronic address:

Background: A consistent proportion of individuals at risk for Alzheimer's disease show intact cognition regardless of the extensive accumulation of amyloid-β (Aβ) peptide in their brain. Several pieces of evidence indicate that overactivation of brain regions negative for Aβ can compensate for the underactivation of Aβ-positive ones to preserve cognition, but the underlying synaptic changes are still unexplored.

Methods: Using Golgi staining, we investigate how dendritic spines rearrange following contextual fear conditioning (CFC) in the hippocampus and amygdala of presymptomatic Tg2576 mice, a genetic model for Aβ accumulation. Read More

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November 2018

Dynamic cortical connectivity alterations associated with Alzheimer's disease: An EEG and fNIRS integration study.

Neuroimage Clin 2018 Dec 3. Epub 2018 Dec 3.

Department of Biomedical Engineering, University of Houston, Houston, USA. Electronic address:

Emerging evidence indicates that cognitive deficits in Alzheimer's disease (AD) are associated with disruptions in brain network. Exploring alterations in the AD brain network is therefore of great importance for understanding and treating the disease. This study employs an integrative functional near-infrared spectroscopy (fNIRS) - electroencephalography (EEG) analysis approach to explore dynamic, regional alterations in the AD-linked brain network. Read More

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December 2018

Dietary changes and cognition over 2 years within a multidomain intervention trial-The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER).

Alzheimers Dement 2018 Nov 23. Epub 2018 Nov 23.

Department of Public Health Solutions, Public Health Promotion Unit, National Institute for Health and Welfare, Helsinki, Finland; Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden.

Introduction: Association between healthy diet and better cognition is well established, but evidence is limited to evaluate the effect of dietary changes adopted in older age.

Methods: We investigated the role of dietary changes in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) with 1260 at-risk participants (60-77 years) who were randomized to intensive multidomain intervention (including dietary counseling) or regular health advice for 2 years. Parallel process latent growth curves of adherence to dietary recommendations and cognitive performance were analyzed. Read More

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November 2018

Aggressive Behaviors in Alzheimer Disease and Mild Cognitive Impairment: Systematic Review and Meta-Analysis.

Am J Geriatr Psychiatry 2018 Oct 19. Epub 2018 Oct 19.

Department of Psychiatry (RY, AT, RJ, SF),Warneford Hospital, University of Oxford, Oxford, England. Electronic address:

Objective: We aim to estimate the risk of perpetrating aggression in Alzheimer disease (AD) and mild cognitive impairment (MCI) by conducting a systematic review and meta-analysis of primary studies.

Methods: A systematic search was conducted in six bibliographic databases according to a preregistered protocol. Studies that reported aggressive behaviors in individuals with AD and MCI compared with healthy individuals or those with other dementia etiologies were identified. Read More

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October 2018

The combination of luteolin and l-theanine improved Alzheimer disease-like symptoms by potentiating hippocampal insulin signaling and decreasing neuroinflammation and norepinephrine degradation in amyloid-β-infused rats.

Nutr Res 2018 Dec 2;60:116-131. Epub 2018 Oct 2.

Department of Food Science & Technology, and Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea.

Luteolin and l-theanine have anti-inflammatory, antioxidant, and possible antidiabetic activities, and they may synergistically protect against dementia. Here, we hypothesized that a combination of luteolin and l-theanine would synergistically act to improve memory function and glucose disturbances in rats infused with amyloid-β, and the mechanisms underlying these actions were investigated. Rats that received an amyloid-β(25-35) infusion into the CA1 region of the hippocampus were fed dextrin (AD-CON), 0. Read More

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December 2018

[Brain insulin signaling and Tau: impact for Alzheimer's disease and Tauopathies].

Med Sci (Paris) 2018 Nov 10;34(11):929-935. Epub 2018 Dec 10.

Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc, « Alzheimer & Tauopathies », LabEx DISTALZ, F-59000 Lille, France.

Alzheimer's disease (AD) is a neurodegenerative disease primarily characterized by cognitive deficits and neuropathological lesions such as Tau aggregates and amyloid plaques, but also associated with metabolic and neuroendocrine abnormalities, such as impairment of cerebral insulin. However, the origin of these symptoms and their relationship to pathology and cognitive disorders remain poorly understood. Insulin is a hormone involved in the control of peripheral and central energy homeostasis, and insulin-resistant state has been linked to increased risk of dementia. Read More

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November 2018

Geriatrics update 2018: Challenges in mental health, mobility, and postdischarge care.

Cleve Clin J Med 2018 Dec;85(12):953-958

Director, Center for Geriatric Medicine, Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.

A review of articles on geriatric topics from 2017 and 2018 revealed evidence supporting exercise for the elderly, early mobility for hospitalized patients, and oral anticoagulant therapy for atrial fibrillation to support cognitive function, and evidence against antipsychotic drugs for dementia-associated behaviors. No silver bullet was found for Alzheimer prevention or therapy. Read More

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December 2018

Development and Validation of a Dementia Risk Prediction Model in the General Population: An Analysis of Three Longitudinal Studies.

Am J Psychiatry 2018 Dec 11:appiajp201818050566. Epub 2018 Dec 11.

The Department of Epidemiology (Licher, Leening, Yilmaz, Wolters, Heeringa, Vernooij, M.K. Ikram, M.A. Ikram), the Department of Neurology (Wolters, M.K. Ikram), the Department of Cardiology (Leening), the Department of Radiology and Nuclear Medicine (Yilmaz, Vernooij), and the Department of General Practice (Bindels), Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands; the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston (Leening, Wolters); the Institute of Health and Society, Newcastle University, Newcastle, U.K. (Stephan); the Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands (Steyerberg); and the Center for Medical Decision Making, Department of Public Health, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands (Steyerberg).

Objective:: Identification of individuals at high risk of dementia is essential for development of prevention strategies, but reliable tools are lacking for risk stratification in the population. The authors developed and validated a prediction model to calculate the 10-year absolute risk of developing dementia in an aging population.

Methods:: In a large, prospective population-based cohort, data were collected on demographic, clinical, neuropsychological, genetic, and neuroimaging parameters from 2,710 nondemented individuals age 60 or older, examined between 1995 and 2011. Read More

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December 2018

Feasibility and Impact of a Multicomponent Exercise Intervention in Patients With Alzheimer's Disease: A Pilot Study.

Am J Alzheimers Dis Other Demen 2018 Dec 9:1533317518813555. Epub 2018 Dec 9.

1 CIAFEL-Research Centre in Physical Activity, Health and Leisure, Porto, Portugal.

This quasi-experimental, nonrandomized study examined the feasibility and impact of a multicomponent (MT) intervention on 7 community-dwelling individuals diagnosed with probable Alzheimer's disease (AD) at mild to moderate stage. During 6 months, patients with AD and their caregivers were submitted to a biweekly exercise program, including muscle strengthening, aerobics, balance, and postural exercises. The following tests were used: Senior Fitness Test and Incremental Treadmill Test, Disability Assessment for Dementia Scale, Alzheimer Disease Assessment Scale-Cognitive, and Quality of Life-Alzheimer's. Read More

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December 2018

Discovery of in-vivo chemical probes for treating Alzheimer´s disease: Dual phosphodiesterase 5 (PDE5) and class I histone deacetylases-selective inhibitors.

ACS Chem Neurosci 2018 Dec 10. Epub 2018 Dec 10.

In order to determine the contributions of histone deacetylase (HDAC) isoforms to the beneficial effects of dual PDE5 and pan-HDAC inhibitors on in vivo models of Alzheimer's disease (AD), we have designed, synthesized and tested novel chemical probes with the desired target compound profile of phosphodiesterase 5 (PDE5)- and class I HDAC-selective inhibitors. Compared to previous hydroxamate-based series, these molecules exhibit longer residence times on HDACs. In this scenario, shorter or longer pre-incubation times may have a significant impact on the IC50 values of these compounds and therefore on their corresponding selectivity profiles on the different HDAC isoforms. Read More

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December 2018

A multifunctional compound ebselen reverses memory impairment, apoptosis and oxidative stress in a mouse model of sporadic Alzheimer's disease.

J Psychiatr Res 2018 Nov 27;109:107-117. Epub 2018 Nov 27.

Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900, Santa Maria, Rio Grande do Sul, Brazil. Electronic address:

Alzheimer 's disease (AD) is characterized by progressive cognitive decline including memory impairment, cortical dysfunction, and neuropsychiatric disturbances. The drug discovery to treat AD consists to develop compounds able to act in multiple molecular targets involved in the pathogenesis of the disease and the repositioning of old drugs for new application. This way, the intracerebroventricular (icv) injection of streptozotocin (STZ) has been used as a metabolic model of sporadic AD. Read More

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November 2018
1 Read

Amyloid-degrading enzymes in Alzheimer´s disease: from molecules to genetic therapy

Rev Med Inst Mex Seguro Soc 2018 11 30;56(4):387-394. Epub 2018 Nov 30.

Universidad Autónoma de Campeche, Facultad de Ciencias Químico Biológicas, Cuerpo Académico Ciencias de la Salud y Biotecnología. Campeche, Campeche, México

Alzheimer’s disease (AD) is the main form of dementia in elderly population worldwide. By 2010 it was estimated that 35.6 million of people were living with this disease, and it was projected that this figure will triple by the year 2050. Read More

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November 2018
2 Reads

Levels of 17β-hydroxysteroid dehydrogenase type 10 in CSF are not a valuable biomarker for multiple sclerosis.

Biomark Med 2018 Dec 6. Epub 2018 Dec 6.

National Institute of Mental Health, 250 67 Klecany, Czech Republic.

Aim: We aimed to characterize the role of mitochondrial 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) overexpression in multiple sclerosis (MS) and to evaluate its use as a biomarker. Materials & methods: We estimated levels of 17β-HSD10, amyloid β 1-42, cyclophilin D, 17β-HSD10-cyclophilin D complexes or 17β-HSD10-parkin complexes in cerebrospinal fluid (CSF) samples.

Results: The increase in 17β-HSD10 levels or in 17β-HSD10-parkin complexes and links to leukocytes were found only in relapsing-remitting MS. Read More

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December 2018

The hidden variables problem in Alzheimer's disease clinical trial design.

Alzheimers Dement (N Y) 2018 13;4:628-635. Epub 2018 Nov 13.

Krembil Research Institute, University Health Network, Toronto, ON, Canada.

As the leading cause of dementia worldwide, Alzheimer's disease has garnered intense academic and clinical interest. Yet, trials in search of a disease-modifying therapy have failed overwhelmingly. We suggest that, in part, this may be attributable to the influence of disruptive variables inherent to the framework of a clinical trial. Read More

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November 2018
1 Read

Cerebrospinal fluid neurogranin/β-site APP-cleaving enzyme 1 predicts cognitive decline in preclinical Alzheimer's disease.

Alzheimers Dement (N Y) 2018 10;4:617-627. Epub 2018 Nov 10.

Department of Neurology, Akershus University Hospital, Lørenskog, Norway.

Introduction: The cerebrospinal fluid neurogranin (Ng)/β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) ratio may reflect synaptic affection resulting from reduced beta-amyloid (Aβ) clearance. We hypothesize that increased Ng/BACE1 ratio predicts the earliest cognitive decline in Alzheimer's disease.

Methods: We compared Ng/BACE1 levels between cases with subjective cognitive decline (n = 18) and mild cognitive impairment (n = 20) both with amyloid plaques and healthy controls (-ε4+, n = 16; -ε4-, n = 20). Read More

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November 2018
2 Reads

Do caregiver profiles predict the use of dementia care services? Findings from the Actifcare study.

Aging Ment Health 2018 Dec 6:1-8. Epub 2018 Dec 6.

a Alzheimer Centre Limburg , Maastricht , Netherlands.

Objectives: Previously developed dementia caregiver profiles defined by caregiver age and burden, have been associated with caregiver quality of life, depression and perseverance time. The current aim was to investigate whether these caregiver profiles could predict subsequent service use. In addition, non-personal (e. Read More

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December 2018

A Comparative Single-Blind Randomized Controlled Trial With Language Training in People With Mild Cognitive Impairment.

Am J Alzheimers Dis Other Demen 2018 Dec 5:1533317518813554. Epub 2018 Dec 5.

1 Greek Alzheimer Association, Thessaloniki, Greece.

Background:: Although cognitive training is effective for people with mild cognitive impairment (MCI), it is not clear which format is more effective.

Objective:: To compare the effectiveness of the same language programs when carried out via computer, paper/pencil and orally in people with MCI.

Methods:: Seventy-one participants with MCI were randomly classified in 3 experimental and 2 control groups. Read More

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December 2018
1 Read

Age-dependent behavioral and biochemical characterization of single APP knock-in mouse (APP) model of Alzheimer's disease.

Neurobiol Aging 2018 Nov 5;75:25-37. Epub 2018 Nov 5.

Canadian Center for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada. Electronic address:

Saito et al developed a novel amyloid precursor protein (APP) knock-in mouse model (APP) for Alzheimer's disease (AD) to overcome the problem of overexpression of APP in available transgenic mouse models. However, this new mouse model for AD is not fully characterized age-dependently with respect to behavioral and biochemical changes. Therefore, in the present study, we performed an age-dependent behavioral and biochemical characterization of this newly developed mouse model. Read More

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November 2018

Sex Differences in the Timing Behavior Performance of 3xTg-AD and Wild-Type Mice in the Peak Interval Procedure.

Behav Brain Res 2018 Nov 30. Epub 2018 Nov 30.

Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address:

We investigated interval timing behavior of 10-month-old male and female 3xTg-AD mice compared with their B6129F2/J wild type controls using the peak interval procedure with a 15 s target interval. Multiple parameters reflecting different aspects of timing performance were extracted from steady-state anticipatory nose-poking behavior using two different approaches: single trial analyses and averaged response curve analyses. These measures can dissociate the differences in performance due to distortions in the interval timing ability or to motivational decline (i. Read More

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November 2018

Association of Cerebrospinal Fluid Neurofilament Light Protein Levels With Cognition in Patients With Dementia, Motor Neuron Disease, and Movement Disorders.

JAMA Neurol 2018 Dec 3. Epub 2018 Dec 3.

Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.

Importance: Neuronal and axonal destruction are hallmarks of neurodegenerative diseases, but it is difficult to estimate the extent and progress of the damage in the disease process.

Objective: To investigate cerebrospinal fluid (CSF) levels of neurofilament light (NFL) protein, a marker of neuroaxonal degeneration, in control participants and patients with dementia, motor neuron disease, and parkinsonian disorders (determined by clinical criteria and autopsy), and determine its association with longitudinal cognitive decline.

Design, Setting, And Participants: In this case-control study, we investigated NFL levels in CSF obtained from controls and patients with several neurodegenerative diseases. Read More

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December 2018

Correlation of In Vivo [18F]Flortaucipir With Postmortem Alzheimer Disease Tau Pathology.

JAMA Neurol 2018 Dec 3. Epub 2018 Dec 3.

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

Importance: In Alzheimer disease (AD), tau filaments form neuronal inclusions in neurites (neuropil threads) and in somata (neurofibrillary tangles), and neurite tau pathology constitutes the most common pathology. Positron emission tomography (PET) ligands have been developed to detect in vivo tau pathology in AD. However, the association of AD tau pathology post mortem with in vivo tau PET retention has not been established. Read More

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December 2018

Gender and Educational Differences in the Association between Lifestyle and Cognitive Decline over 10 Years: The Doetinchem Cohort Study.

J Alzheimers Dis 2018 Nov 28. Epub 2018 Nov 28.

Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.

Background: Several modifiable risk factors for cognitive decline have been identified, but whether differences by gender and educational level exist is unclear.

Objective: The present study aims to clarify this by prospectively investigating the relationship between health- and lifestyle factors and cognitive functioning in different subgroups defined by gender and educational level.

Methods: 2,347 cognitive healthy individuals (mean age = 54. Read More

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November 2018
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A δ Homolog for Dementia Case Finding with Replication in the Alzheimer's Disease Neuroimaging Initiative.

J Alzheimers Dis 2018 Nov 28. Epub 2018 Nov 28.

Departments of Family and Community Medicine, The University of Texas Health Science Center, San Antonio, TX, USA.

Dementia can be empirically described by the latent dementia phenotype "δ" and its various composite "homologs". We have explored δ's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Read More

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November 2018