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Current Alzheimer Research

Slavka Hamulakova, Ladislav Janovec, Ondrej Soukup, Daniel Jun, Jana Janockova, Martina Hrabinova, Vendula Sepsova, Kamil Kuca
BACKGROUND: The design of new heterodimeric dual binding site acetylcholinesterase inhibitors constitutes the main goal directed to the development of new anticholinesterase agents with expanded pharmacological profile. Multi-target compounds are usually designed by combining in a hybrid molecule two or more pharmacophoric moieties that are known to enable interaction with the selected molecular targets. METHODS: All compounds were tested for their inhibitory activity on human AChE/BChE...
July 10, 2018: Current Alzheimer Research
Dimitrios Kapogiannis, Mohamad El Haj
OBJECTIVES: research suggests beneficial effects of minimal interference on item memory in mild Alzheimer's disease (AD). We conducted a study to test whether these beneficial effects extend to source memory, i.e., the ability to remember the episodic context in which an information was previously acquired. METHODS: twenty-six mild AD participants and 28 controls manipulated six objects or watched the experimenter manipulating six other objects. After immediate item recall ("what were the items?") and source recall ("by whom the items were previously manipulated?"), an interference or a minimal interference condition was administrated...
July 10, 2018: Current Alzheimer Research
Lu Fu, Yao Sun, Yongqing Guo, Bin Yu, Haihong Zhang, Jiaxin Wu, Xianghui Yu, Hui Wu, Wei Kong
widely used mouse models for studying Alzheimer's disease (AD) pathogenesis and preclinical studies of AD therapeutic approaches. OBJECTIVE: In this study, we systematically investigated cognitive decline, amyloid-β (Aβ) deposition and cerebral or Aβ serum levels as well as the relationships among these measures in APPswe/PS1dE9 transgenic mice. METHODS: APPswe/PS1dE9 mice were separated into four equal age cohorts (4, 6, 9, and 12 months). We assessed cognitive capacity, deposited plaques, and the levels of Aβ40/Aβ42 in brain tissue and serum of mice at different ages...
July 8, 2018: Current Alzheimer Research
Naohito Takenoshita, Raita Fukasawa, Yusuke Ogawa, Soichiro Shimizu, Takahiko Umahara, Kenji Ishii, Hitoshi Shimada, Makoto Higuchi, Tetsuya Suhara, Haruo Hanyu
BACKGROUND: Type 2 diabetes mellitus (DM) has been shown to increase the risk for cognitive decline and dementia, such as Alzheimer disease (AD) and vascular dementia (VaD). In addition to AD and VaD, there may be a dementia subgroup associated with specific DM-related metabolic abnormalities rather than AD pathology or cerebrovascular disease, referred to as diabetes-related dementia (DrD). METHODS: We studied 11C-PiB and 11C-PBB3 positron emission tomography (PET) in 31 subjects with DrD and 5 subjects with AD associated with DM to assess amyloid and tau deposits in the brain...
July 8, 2018: Current Alzheimer Research
Zhiyou Cai, Chuanling Wang, Wenbo He, Yi Chen
BACKGROUND: Berberine (BBR) has neuroprotective effects on many brain diseases, including Alzheimer's disease (AD). Amyloid -beta (Aβ) senile plaque is the most classical pathological hallmarks of AD. Aβ produces from a sequential cleavage by β-secretase (beta-site amyloid precursor protein cleaving enzyme 1, BACE1) and γ-secretase. The aim of our work was to investigate whether the neuroprotective effects of BBR on AD is related to inhibiting Aβ pathology. METHODS: The cognitive function of mice was assessed by the Morris water maze (MWM) test...
July 1, 2018: Current Alzheimer Research
Katherine E Irimata, Brittany N Dugger, Jeffrey R Wilson
BACKGROUND: Studies have shown select associations between cardiovascular risk factors and dementia, but most focus on Alzheimer's disease (AD). OBJECTIVE: We enhance these works by evaluating the relationship between the presence of cardiovascular risk factors and the rate of cognitive decline, measured using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR-SUM) on four common dementia subtypes (AD, dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VaD), as well as non-demented elderly individuals (normal))...
July 1, 2018: Current Alzheimer Research
Carlo Lazzari
BACKGROUND: Caregivers of persons with Alzheimer's disease (AD) often experience feelings of lack of support and information from specialists when operating in real scenarios events, inclusive of old-age psychiatric wards, care homes, community, and patient's home. OBJECTIVE: AD caregivers can provide narrative about what issues need to be addressed in Ecological Momentary Assessment (EMA) to capture real-time and real-scenario needs in AD caregiving, and Ecological Momentary Interventions as online e-learning to assist in areas of concerns...
July 1, 2018: Current Alzheimer Research
Cecilia Camarda, Paola Torelli, Carmela Pipia, Iacopo Battaglini, Delia Azzarello, Rosamaria Rosano, Caterina Claudia Ventimiglia, Gianluca Sottile, Giovanna Cilluffo, Rosolino Camarda
BACKGROUND: Mild Parkinsonian signs (MPS) are commonly seen in aging, and have been related to cerebral small vessel diseases (SVD) with no univocal results. OBJECTIVE: The aim of this study is to investigate the cross-sectional relation between MPS and white matter hyperintensities (WMH), lacunes, caudate atrophy, and global cerebral atrophy in a large cohort of neurologically and cognitively healthy (NCH) aging individuals. METHOD: 1,219 NCH individuals were included in the analysis, and underwent standard brain MRI...
July 1, 2018: Current Alzheimer Research
F Ruffinatti, L Tapella, I Gregnanin, A Stevano, G Chiorino, P L Canonico, C Distasi, A A Genazzani, D Lim
BACKGROUND: It is well known that alterations in astrocytes occur in Alzheimer's Disease and reactive astrogliosis is one of the hallmarks of the disease. Recently, data has emerged that suggests that alterations in astrocytes may also occur early in the pathogenesis of the disease. OBJECTIVE: The aim of present work was to characterize the transcriptional alterations occurring in cultured astrocytes from 3xTg-AD mouse pups compared to control non-transgenic mice...
June 12, 2018: Current Alzheimer Research
Rafael Blesa, Kazuhiro Toriyama, Kengo Ueda, Sean Knox, George Grossberg
INTRODUCTION: Alzheimer's disease (AD) is the most common cause of dementia, characterized by a progressive decline in cognition and function. Current treatment options for AD include the cholinesterase inhibitors (ChEIs) donepezil, galantamine, and rivastigmine, as well as the N-methyl-D-aspartate receptor antagonist memantine. Treatment guidelines recommend the use of ChEIs as standard of care first-line therapy. Several randomized clinical studies have demonstrated the benefits of ChEIs on cognition, global function, behavior and activities of daily living...
June 12, 2018: Current Alzheimer Research
Melissa Wee, Fariba Chegini, John H T Power, Shohreh Majd
BACKGROUND: Alzheimer's disease (AD) pathology consists of intraneuronal neurofibrillary tangles, made of hyperphosphorylated tau and extracellular accumulation of beta amyloid (Aβ) in Aβ plaques. There is an extensive debate as to which pathology initiates and responsible for cellular loss in AD. METHODS: Using confocal and light microscopy, post mortem brains from control and AD cases, an antibody to SOD2 as a marker for mitochondria and an antibody to all forms of tau, we analyzed mitochondrial density in tau positive neurons along with nuclear degradation by calculating the raw integrative density...
June 12, 2018: Current Alzheimer Research
Katharina Brueggen, Martin Dyrba, Ingo Kilimann, Judith Henf, Wolfgang Hoffmann, Jochen R Thyrian, Stefan Teipel
BACKGROUND: Hippocampal mean diffusivity (MD) measured by diffusion-tensor imaging is a promising diagnostic marker for Mild Cognitive Impairment (MCI) and dementia. Its performance has yet to be evaluated in primary care patients, who vary systematically from patients visiting specialized care settings. OBJECTIVE: We assessed the diagnostic accuracy of hippocampus diffusivity for detecting MCI and dementia in a sample recruited from primary care, compared to a sample from specialized care...
June 12, 2018: Current Alzheimer Research
Giacobini Ezio, Pepeu Giancarlo
This review has two aims. First, to examine whether or not sex and gender may influence the brain cholinergic system in animals and in humans. Second, to examine the available evidence of sexually dimorphic response to the therapeutic and toxic effects of cholinesterase inhibitors. Animal research reveals no marked difference in the general morphology of the brain cholinergic system but subtle functional gender differences have been reported. In humans, gender differences in nucleus basalis of Meynert (NBM) exist...
June 12, 2018: Current Alzheimer Research
Martina Zverova, Eva Kitzlerova, Zdenek Fisar, Roman Jirak, Jana Hroudova, Hana Benakova, Petra Lelkova, Pavel Martasek, Jiri Raboch
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin are presumed to be risk factors or biomarkers for stress- and age-related disorders. OBJECTIVE: The interplay between the APOE genotype and plasma biomarkers was examined in patients with AD presenting with or without depression to contribute to understanding the interdependence of various molecular mechanisms in the pathophysiology of AD...
May 31, 2018: Current Alzheimer Research
Lili Wan, Jin Lu, Jianliang Fu, Jinlu Huang, Quanjun Yang, Bo Xin, Li Chen, Yan Huo, Yuan Zhong, Cheng Guo
BACKGROUND: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by a multi-factorial etiology that is not completely understood. Donepezil is a first-line acetylcholinesterase inhibitor used for the treatment of AD that has been found, in addition to its potent acetylcholinesterase inhibitory effect, to act through other non-cholinergic mechanisms such as affecting mitochondrial biogenesis through peroxisome proliferator-activated receptor gamma coactivator (PGC1α)...
May 31, 2018: Current Alzheimer Research
Ignazio Vecchio, Cristina Tornali, Giulia Malaguarnera, Nicola Luigi Bragazzi, Michele Malaguarnera
The progressive supranuclear palsy is a progressive neurodegenerative disease characterized by Parkinsonism, oculomotor abnormalities, early postural instability and cognitive impairment. Neurodegeneration in PSP is associated with tau protein, but the mechanisms by which tau abnormalities lead to cell dysfunction and death are not well understood. Neuro-behavioural problems related to the fear and loss of autonomy can determinate many bioethical implications. Careful planning involving patients' families, academic and industry researchers were necessary to ensure improvement in quality of life...
May 6, 2018: Current Alzheimer Research
Carina Wattmo, Elisabet Londos, Lennart Minthon
BACKGROUND: A varying response to cholinesterase inhibitor (ChEI) treatment has been reported among patients with Alzheimer's disease (AD). Whether the individual-specific response directly affects time to nursing home placement (NHP) was not investigated. OBJECTIVE: We examined the relationship between the 6-month response to ChEI and institutionalization. METHODS: In a prospective, observational, multicenter study, 881 outpatients with a clinical AD diagnosis and a Mini-Mental State Examination score of 10-26 at the start of ChEI therapy (baseline) were included...
May 6, 2018: Current Alzheimer Research
Sudipta Chakrabarti, Malabendu Jana, Avik Roy, Kalipada Pahan
Neuroinflammation plays an important role in the pathogenesis of various neurodegenerative diseases including Alzheimer's disease (AD). Suppressor of cytokine signaling 3 (SOCS3) is an anti-inflammatory molecule that suppresses cytokine signaling and inflammatory gene expression in different cells including microglia. However, pathways through which SOCS3 could be upregulated are poorly described. Cinnamic acid is a metabolite of cinnamon, a natural compound that is being widely used all over the world as a spice or flavoring agent...
May 6, 2018: Current Alzheimer Research
David Perpetuini, Daniela Cardone, Roberta Bucco, Michele Zito, Arcangelo Merla
Background - Alzheimer's disease (AD) is a form of dementia characterized by failures of memory that becomes more severe with the progression of the disease. The Free and Cued Selective Reminding Test (FCSRT) is a clinical test used to evaluate such a deficit. However, since the cognitive performances could depend also on the psychophysiological state of the individual, it is important to monitor that state through the peripheral autonomic activity during the execution of the test. Thermal infrared imaging has been used for this kind of assessment in order to preserve the free and unbiased interaction between doctor and patient, thanks to the contactless features of the technique...
May 3, 2018: Current Alzheimer Research
Yue Ruan, Jun Tang, Xiaofei Guo, Kelei Li, Duo Li
BACKGROUND: Epidemiological studies showed that dietary fat intake was associated with Alzheimer's disease (AD) and dementia risk, however, the association remain inconsistent. This meta-analysis aimed to systematically examine the association of dietary fat intake with AD and dementia risk. METHODS: We have systematically searched PubMed, Embase and the Cochrane Library up to May 1st 2017. Prospective cohort studies were included if they reported on the association of dietary fat intake with AD and dementia risk...
April 27, 2018: Current Alzheimer Research
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