Journal ArticleDOI
Memantine in Moderate-to-Severe Alzheimer's Disease
Barry Reisberg,Rachelle S. Doody,Albrecht Stöffler,Frederick A. Schmitt,Steven H. Ferris,Hans Jörg Möbius +5 more
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TLDR
Antiglutamatergic treatment reduced clinical deterioration in moderate-to-severe Alzheimer's disease, a phase associated with distress for patients and burden on caregivers, for which other treatments are not available.Abstract:
Background Overstimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate is implicated in neurodegenerative disorders. Accordingly, we investigated memantine, an NMDA antagonist, for the treatment of Alzheimer's disease. Methods Patients with moderate-to-severe Alzheimer's disease were randomly assigned to receive placebo or 20 mg of memantine daily for 28 weeks. The primary efficacy variables were the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (ADCS-ADLsev). The secondary efficacy end points included the Severe Impairment Battery and other measures of cognition, function, and behavior. Treatment differences between base line and the end point were assessed. Missing observations were imputed by using the most recent previous observation (the last observation carried forward). The results were also analyzed with only the observed values included,...read more
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Neurodegenerative diseases and oxidative stress.
TL;DR: Oxidative stress has been implicated in the progression of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and different strategies, including novel metal–protein attenuating compounds aimed at a variety of targets have shown promise in clinical studies.
Journal ArticleDOI
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Stephen F. Traynelis,Lonnie P. Wollmuth,Chris J. McBain,Frank S. Menniti,Katie M. Vance,Kevin K. Ogden,Kasper B. Hansen,Hongjie Yuan,Scott J. Myers,Raymond Dingledine +9 more
TL;DR: This review discusses International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
Journal ArticleDOI
Intracellular amyloid-β in Alzheimer's disease
TL;DR: Although the classical view is that Aβ is deposited extracellularly, emerging evidence from transgenic mice and human patients indicates that this peptide can also accumulate intraneuronally, which may contribute to disease progression.
Journal ArticleDOI
Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial.
Pierre N. Tariot,Martin R. Farlow,George T. Grossberg,Stephen M. Graham,Scott D. McDonald,Ivan Gergel +5 more
TL;DR: In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated.
Journal ArticleDOI
Alzheimer's disease: clinical trials and drug development
Francesca Mangialasche,Francesca Mangialasche,Alina Solomon,Alina Solomon,Bengt Winblad,Patrizia Mecocci,Miia Kivipelto,Miia Kivipelto +7 more
TL;DR: It is acknowledged that a single cure for Alzheimer's disease is unlikely to be found and that the approach to drug development for this disorder needs to be reconsidered, but several promising randomised controlled trials are ongoing and increased collaboration between pharmaceutical companies, basic researchers, and clinical researchers has the potential to bring us closer to developing an optimum pharmaceutical approach.
References
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Journal ArticleDOI
“Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician
Marshal F. Folstein,Marshal F. Folstein,Susan E B Folstein,Susan E B Folstein,Paul R. McHugh,Paul R. McHugh +5 more
TL;DR: A simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
A practical method for grading the cognitive state of patients for the clinician
TL;DR: The Mini-Mental State (MMS) as mentioned in this paper is a simplified version of the standard WAIS with eleven questions and requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
Journal ArticleDOI
Clinical diagnosis of Alzheimer's disease : report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
Guy M. McKhann,David A. Drachman,Marshall F. Folstein,Robert Katzman,Donald L. Price,Emanuel M. Stadlan +5 more
TL;DR: The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information becomes available.
Journal ArticleDOI
The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia
Jeffrey L. Cummings,Michael S. Mega,Kevin F. Gray,S. Rosenberg-Thompson,Daniela Carusi,Jeffrey Gornbein +5 more
TL;DR: The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.