The Experts below are selected from a list of 201963 Experts worldwide ranked by ideXlab platform
Costantino Iadecola - One of the best experts on this subject based on the ideXlab platform.
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dietary salt promotes Cognitive Impairment through tau phosphorylation
Nature, 2019Co-Authors: Giuseppe Faraco, Karin Hochrainer, Steven G Segarra, Samantha Schaeffer, Monica M Santisteban, Ajay Menon, Hong Jiang, David M Holtzman, Josef Anrather, Costantino IadecolaAbstract:Dietary habits and vascular risk factors promote both Alzheimer’s disease and Cognitive Impairment caused by vascular factors1–3. Furthermore, accumulation of hyperphosphorylated tau, a microtubule-associated protein and a hallmark of Alzheimer’s pathology4, is also linked to vascular Cognitive Impairment5,6. In mice, a salt-rich diet leads to Cognitive dysfunction associated with a nitric oxide deficit in cerebral endothelial cells and cerebral hypoperfusion7. Here we report that dietary salt induces hyperphosphorylation of tau followed by Cognitive dysfunction in mice, and that these effects are prevented by restoring endothelial nitric oxide production. The nitric oxide deficiency reduces neuronal calpain nitrosylation and results in enzyme activation, which, in turn, leads to tau phosphorylation by activating cyclin-dependent kinase 5. Salt-induced Cognitive Impairment is not observed in tau-null mice or in mice treated with anti-tau antibodies, despite persistent cerebral hypoperfusion and neurovascular dysfunction. These findings identify a causal link between dietary salt, endothelial dysfunction and tau pathology, independent of haemodynamic insufficiency. Avoidance of excessive salt intake and maintenance of vascular health may help to stave off the vascular and neurodegenerative pathologies that underlie dementia in the elderly. A high-salt diet in mice induces Cognitive Impairment through a signalling cascade that culminates in increased phosphorylation of tau.
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dietary salt promotes Cognitive Impairment through tau phosphorylation
bioRxiv, 2018Co-Authors: Giuseppe Faraco, Karin Hochrainer, Steven G Segarra, Samantha Schaeffer, Monica M Santisteban, Ajay Menon, Hong Jiang, David M Holtzman, Josef Anrather, Costantino IadecolaAbstract:Dietary habits and vascular risk factors promote both Alzheimer's disease and Cognitive Impairment caused by vascular factors. Furthermore, accumulation of hyperphosphorylated tau, a microtubule associated protein and a hallmark of Alzheimer's pathology, is also linked to vascular Cognitive Impairment. In mice, a salt-rich diet leads to Cognitive dysfunction associated with a nitric oxide deficit in cerebral endothelial cells and cerebral hypoperfusion. Here we report that dietary salt induces tau hyperphosphorylation followed by Cognitive dysfunction, effects prevented by restoring endothelial nitric oxide production. The nitric oxide deficiency reduces neuronal calpain nitrosylation resulting in enzyme activation, which, in turn, leads to tau phosphorylation by activating cyclin dependent kinase-5. Salt-induced Cognitive Impairment is not observed in tau-null mice or in mice treated with anti-tau antibodies, despite persistent cerebral hypoperfusion and neurovascular dysfunction. These findings unveil a causal link between dietary salt, endothelial dysfunction and tau pathology, independent of hemodynamic insufficiency. Avoiding excessive salt intake and maintaining vascular health may help stave off vascular and neurodegenerative pathologies underlying late-life dementia.
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national institute of neurological disorders and stroke canadian stroke network vascular Cognitive Impairment harmonization standards
Stroke, 2006Co-Authors: Vladimir Hachinski, Charles Decarli, Costantino Iadecola, Ronald Carl Petersen, Monique M B Breteler, David L Nyenhuis, Sandra E Black, William J Powers, Jose G Merino, Raj N KalariaAbstract:Background and Purpose—One in 3 individuals will experience a stroke, dementia or both. Moreover, twice as many individuals will have Cognitive Impairment short of dementia as either stroke or dementia. The commonly used stroke scales do not measure cognition, while dementia criteria focus on the late stages of Cognitive Impairment, and are heavily biased toward the diagnosis of Alzheimer disease. No commonly agreed standards exist for identifying and describing individuals with Cognitive Impairment, particularly in the early stages, and especially with Cognitive Impairment related to vascular factors, or vascular Cognitive Impairment. Methods—The National Institute for Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) convened researchers in clinical diagnosis, epidemiology, neuropsychology, brain imaging, neuropathology, experimental models, biomarkers, genetics, and clinical trials to recommend minimum, common, clinical and research standards for the description and study of vascular Cognitive Impairment. Results—The results of these discussions are reported herein. Conclusions—The development of common standards represents a first step in a process of use, validation and refinement. Using the same standards will help identify individuals in the early stages of Cognitive Impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress. (Stroke. 2006;37:2220-2241.)
Ronald C Petersen - One of the best experts on this subject based on the ideXlab platform.
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Mild Cognitive Impairment: ten years later.
Archives of neurology, 2009Co-Authors: Ronald C Petersen, Bradley F. Boeve, David S. Knopman, Rosebud O. Roberts, Yonas E. Geda, Robert J. Ivnik, Glenn E. Smith, Clifford R. JackAbstract:In the past 10 years, there has been a virtual explosion in the literature concerning the construct of mild Cognitive Impairment. The interest in this topic demonstrates the increasing emphasis on the identification of the earliest features of Cognitive disorders such as Alzheimer disease and other dementias. Mild Cognitive Impairment represents the earliest clinical features of these conditions and, hence, has become a focus of clinical, epidemiologic, neuroimaging, biomarker, neuropathological, disease mechanism, and clinical trials research. This review summarizes the progress that has been made while also recognizing the challenges that remain.
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mild Cognitive Impairment
The Lancet, 2006Co-Authors: Serge Gauthier, Barry Reisberg, Michael Zaudig, Ronald C Petersen, Karen Ritchie, Karl Broich, Sylvie Belleville, Henry Brodaty, David A Bennett, Howard ChertkowAbstract:Mild Cognitive Impairment is a syndrome defined as Cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild Cognitive Impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild Cognitive Impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild Cognitive Impairment has a high risk of progression to Alzheimer's disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild Cognitive Impairment need to be studied as potential prodromes of Alzheimer's disease and other types of dementia.
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mild Cognitive Impairment as a diagnostic entity
Journal of Internal Medicine, 2004Co-Authors: Ronald C PetersenAbstract:The concept of Cognitive Impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild Cognitive Impairment (MCI) has been proposed to designate an early, but abnormal, state of Cognitive Impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.
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mild Cognitive Impairment aging to alzheimer s disease
2003Co-Authors: Ronald C PetersenAbstract:1. Conceptual Overview 2. Clinical features 3. Neuropsychiatric symptoms 4. Normative neuropsychology in ageing and Mild Cognitive Impairment 5. Optimizing Cognitive test norms for detection 6. Magnetic resonance imaging 7. Functional imaging 8. Spectrum of pathology 9. Neuropathological changes in normal aging, mild Cognitive Impairment and Alzheimer's disease 10. Biological markers 11. Clinical evaluation 12. Treatment of mild Cognitive Impairment and prospects for prevention of Alzheimer's disease
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Current concepts in mild Cognitive Impairment.
Archives of neurology, 2001Co-Authors: Ronald C Petersen, Karen Ritchie, Rachelle S. Doody, Alexander Kurz, Richard C. Mohs, John C. Morris, Peter V. Rabins, Martin N. Rossor, Leon J. Thal, Bengt WinbladAbstract:The field of aging and dementia is focusing on the characterization of the earliest stages of Cognitive Impairment. Recent research has identified a transitional state between the Cognitive changes of normal aging and Alzheimer's disease (AD), known as mild Cognitive Impairment (MCI). Mild Cognitive Impairment refers to the clinical condition between normal aging and AD in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. When these persons are observed longitudinally, they progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals. Consequently, this condition has been recognized as suitable for possible therapeutic intervention, and several multicenter international treatment trials are under way. Because this is a topic of intense interest, a group of experts on aging and MCI from around the world in the fields of neurology, psychiatry, geriatrics, neuropsychology, neuroimaging, neuropathology, clinical trials, and ethics was convened to summarize the current state of the field of MCI. Participants reviewed the world scientific literature on aging and MCI and summarized the various topics with respect to available evidence on MCI. Diagnostic criteria and clinical outcomes of these subjects are available in the literature. Mild Cognitive Impairment is believed to be a high-risk condition for the development of clinically probable AD. Heterogeneity in the use of the term was recognized, and subclassifications were suggested. While no treatments are recommended for MCI currently, clinical trials regarding potential therapies are under way. Recommendations concerning ethical issues in the diagnosis and the management of subjects with MCI were made.
Raj N Kalaria - One of the best experts on this subject based on the ideXlab platform.
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stroke injury Cognitive Impairment and vascular dementia
Biochimica et Biophysica Acta, 2016Co-Authors: Raj N Kalaria, Rufus Olusola Akinyemi, Masafumi IharaAbstract:The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25-30% of ischaemic stroke survivors develop immediate or delayed vascular Cognitive Impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of Cognitive disorders. States of Cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for Cognitive Impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood-brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of Cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
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national institute of neurological disorders and stroke canadian stroke network vascular Cognitive Impairment harmonization standards
Stroke, 2006Co-Authors: Vladimir Hachinski, Charles Decarli, Costantino Iadecola, Ronald Carl Petersen, Monique M B Breteler, David L Nyenhuis, Sandra E Black, William J Powers, Jose G Merino, Raj N KalariaAbstract:Background and Purpose—One in 3 individuals will experience a stroke, dementia or both. Moreover, twice as many individuals will have Cognitive Impairment short of dementia as either stroke or dementia. The commonly used stroke scales do not measure cognition, while dementia criteria focus on the late stages of Cognitive Impairment, and are heavily biased toward the diagnosis of Alzheimer disease. No commonly agreed standards exist for identifying and describing individuals with Cognitive Impairment, particularly in the early stages, and especially with Cognitive Impairment related to vascular factors, or vascular Cognitive Impairment. Methods—The National Institute for Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) convened researchers in clinical diagnosis, epidemiology, neuropsychology, brain imaging, neuropathology, experimental models, biomarkers, genetics, and clinical trials to recommend minimum, common, clinical and research standards for the description and study of vascular Cognitive Impairment. Results—The results of these discussions are reported herein. Conclusions—The development of common standards represents a first step in a process of use, validation and refinement. Using the same standards will help identify individuals in the early stages of Cognitive Impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress. (Stroke. 2006;37:2220-2241.)
Jeremy N Ruskin - One of the best experts on this subject based on the ideXlab platform.
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Cognitive Impairment associated with atrial fibrillation a meta analysis
Annals of Internal Medicine, 2013Co-Authors: Shadi Kalantarian, Theodore A Stern, Moussa Mansour, Jeremy N RuskinAbstract:Background Atrial fibrillation (AF) has been linked with an increased risk of Cognitive Impairment and dementia.
Harry V Vinters - One of the best experts on this subject based on the ideXlab platform.
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pet of brain amyloid and tau in mild Cognitive Impairment
The New England Journal of Medicine, 2006Co-Authors: Gary W Small, Vladimir Kepe, Linda M Ercoli, Prabha Siddarth, Susan Y Bookheimer, Karen J Miller, Helen Lavretsky, Alison C Burggren, Greg M Cole, Harry V VintersAbstract:Background Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild Cognitive Impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics. Methods We enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and positron-emission tomography (PET). On the basis of Cognitive testing, 25 volunteers were classified as having Alzheimer's disease, 28 as having mild Cognitive Impairment, and 30 as having no Cognitive Impairment (healthy controls). PET was performed after injection of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, an...
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pet of brain amyloid and tau in mild Cognitive Impairment
The New England Journal of Medicine, 2006Co-Authors: Gary W Small, Vladimir Kepe, Linda M Ercoli, Prabha Siddarth, Susan Y Bookheimer, Karen J Miller, Helen Lavretsky, Alison C Burggren, Greg M Cole, Harry V VintersAbstract:Background Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild Cognitive Impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics. Methods We enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and positron-emission tomography (PET). On the basis of Cognitive testing, 25 volunteers were classified as having Alzheimer's disease, 28 as having mild Cognitive Impairment, and 30 as having no Cognitive Impairment (healthy controls). PET was performed after injection of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, an...
