scholarly journals Broader Considerations of Higher Doses of Donepezil in the Treatment of Mild, Moderate, and Severe Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Camryn Berk ◽  
Marwan Sabbagh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Nicotinic Receptor ◽  
Acetylcholinesterase Inhibitor ◽  
Symptomatic Treatment ◽  
Mechanisms Of Action ◽  
Receptor Stimulation ◽  
App Processing ◽  
Higher Doses

Donepezil, a highly selective acetylcholinesterase inhibitor (AChEI), is approved as a symptomatic treatment mild, moderate, and severe Alzheimer's disease (AD). Donepezil exerts its treatment effect through multiple mechanisms of action including nicotinic receptor stimulation, mitigation of excitotoxicity, and influencing APP processing. The use of donepezil at higher doses is justified given the worsening cholinergic deficit as the disease advances. Donepezil has been investigated in several clinical trials of subjects with moderate-to-severe AD. While the side effects are class specific (cholinergically driven), demonstrable benefit has been shown at the 10 mg dose and the 23 mg doses. Here, we review the clinical justification, efficacy, safety, and tolerability of use of donepezil in the treatment of moderate-to-severe AD.

Revealing the mechanistic pathway of cholinergic inhibition of Alzheimer's disease by donepezil: a metadynamics simulation study

2019 ◽  
Vol 21 (25) ◽  
pp. 13578-13589 ◽  
Author(s):  
Shibaji Ghosh ◽  
Kalyanashis Jana ◽  
Bishwajit Ganguly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Simulation Study ◽  
Acetylcholinesterase Inhibitor ◽  
Symptomatic Treatment ◽  
Mechanistic Pathway

Donepezil, an acetylcholinesterase inhibitor, is an approved drug for the symptomatic treatment of Alzheimer's disease (AD).

Enhancing Therapeutic Efficacy of Donepezil by Combined Therapy; A Comprehensive Review

2020 ◽  
Vol 26 ◽  
Author(s):  
Xi Rong ◽  
Liwei Jiang ◽  
Meijie Qu ◽  
Syed Shams ul Hassan ◽  
Zongchao Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Dominant Role ◽  
Combined Therapy ◽  
Acetylcholinesterase Inhibitor ◽  
Symptomatic Relief ◽  
Current Status ◽  
Disease Modifying Agents

: Combination therapy involving different therapeutic strategies mostly provides more rapid and effective results as compared to monotherapy in diverse areas of clinical practice. The most worldwide famous acetylcholinesterase inhibitor (AChEIs) donepezil for its dominant role in Alzheimer’s disease (AD) has also attracted the eyes of many pharmaceuticals regarding its promising pharmacological potencies such as neuroprotective, muscle relaxant, and sleep. Recently a combination of donepezil with other agents has displayed better desirable results in the management of several disorders, including most common Alzheimer’s disease (AD). This study encircles all the data regarding the therapeutic effect of donepezil in its combination with other agents and explains its therapeutic targets, mode of action. Furthermore, this review also puts light on the current status of donepezil with other agents in clinical trials. The combo therapy of donepezil with symptomatic relief drugs and disease-modifying agents opens a new road for the treatment of multiple pathological disorders. To best known to our knowledge, this is the first report encircling all the pharmacologic effects of donepezil in its combination therapy with other agents and their current status in clinical trials.

Memantine and Acetylcholinesterase Inhibitor Use in Alzheimer’s Disease Clinical Trials: Potential for Confounding by Indication

2019 ◽  
Vol 67 (2) ◽  
pp. 707-713 ◽  
Author(s):  
Branko N. Huisa ◽  
Ronald G. Thomas ◽  
Shelia Jin ◽  
Tilman Oltersdorf ◽  
Curtis Taylor ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Acetylcholinesterase Inhibitor ◽  
Confounding By Indication

THE PATIENT IN YOUR ALZHEIMER’S DISEASE STUDY MAY BE IN ANOTHER: DUPLICATION AND DECEPTION IN CLINICAL TRIALS OF ALZHEIMER’S DISEASE

2020 ◽  
pp. 1-4
Author(s):  
T. Shiovitz ◽  
B. Steinmiller ◽  
C. Steinmetz ◽  
S. Perez ◽  
R. Oseas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Active Treatment ◽  
Memory Loss ◽  
Mechanisms Of Action ◽  
Efficacy And Safety ◽  
Significant Issue ◽  
Disease Study ◽  
Safety Signals

Duplicate and deceptive subjects, a significant issue in CNS studies, are not often considered in Alzheimer’s Disease (AD) clinical trials. However, AD patients and their study partners may be motivated to take advantage of different mechanisms of action, increase odds of receiving active treatment, and/or obtain financial compensation, which may lead them to participate in multiple studies. CTSdatabase reviewed memory loss subjects (n=1087) from January 2017 through May 2019 to determine how many attempted to screen at multiple sites. 117 subjects (10.8%) visited more than one site within two years. When these potential AD subjects went to additional sites, it was predominantly for non-memory indications (often MDD or schizophrenia). For those that participated in studies, the rate of duplication approached 4% of screened AD subjects. This data indicates that significant numbers of AD subjects attempt to enroll at multiple sites, which confounds efficacy and safety signals in clinical trials.

scholarly journals Efficacy of Memantine, Donepezil, or Their Association in Moderate-Severe Alzheimer’s Disease: A Review of Clinical Trials

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ivana Molino ◽  
Luisa Colucci ◽  
Angiola M. Fasanaro ◽  
Enea Traini ◽  
Francesco Amenta
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Symptomatic Treatment ◽  
Assessment Tools ◽  
Double Blind ◽  
The Usa ◽  
High Doses ◽  
Short Time ◽  
Che Inhibitors

Background. Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors (Is) and memantine are licensed for symptomatic treatment of mild-moderate and moderate-severe forms of Alzheimer’s disease (AD), respectively. High doses of the AChE-I donepezil were licensed in the USA for moderate-severe AD, and the association AChE/ChE-Is plus memantine was proposed for AD at this stage.Objectives. This paper has reviewed evidence from clinical trials of the effectiveness of memantine, donepezil, or the two drugs in association in managing moderate-severe AD.Method. Double-blind, placebo-controlled randomized trials (RCTs) using memantine or donepezil alone or in association versus placebo in moderate-severe AD were reviewed. Analysis done in January 2013 considered the years 2007–2012.Results and Conclusion. Only 83 of the 941 papers selected were considered relevant, and only 13 met the criterion of “adequacy and representativeness.” Memantine and donepezil lead to improvements in moderate-to-severe AD and the choice between the compounds should be based on their contraindications more than on disease severity. No evidence was found of advantages of the association of memantine-donepezil. The heterogeneity of conditions explored by RCTs, the relatively short time of observation (24–52 weeks), and the different cognitive assessment tools used did not allow comparing properly different trials.

The involvement of the GGA protein family in BACE transport and APP processing in Alzheimer's disease

2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
C Steinmetz ◽  
B von Einem ◽  
D Schwanzar ◽  
F Dolp ◽  
A.C Ludolph ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Family ◽  
App Processing

An Insight in Pathophysiological Mechanism of Alzheimer’s Disease and its Management using Plant Natural Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Zeba Firdaus ◽  
Tryambak Deo Singh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Side Effects ◽  
Neuronal Degeneration ◽  
Acetylcholinesterase Inhibitor ◽  
Pathophysiological Mechanism ◽  
Limited Effectiveness ◽  
Drug Development Research ◽  
Sites Of Action

: Alzheimer’s disease (AD) is an age-associated nervous system disorder and a leading cause of dementia worldwide. Clinically it is described by cognitive impairment, and pathophysiologically by deposition of amyloid plaques and neurofibrillary tangles in the brain and neurodegeneration. This article reviews the pathophysiology, course of neuronal degeneration, and the various possible hypothesis of AD progression. These hypotheses include amyloid cascade, tau hyperphosphorylation, cholinergic disruption, metal dysregulation, vascular dysfunction, oxidative stress, and neuroinflammation. There is an exponential increase in the occurrence of the AD in recent few years that indicate an urgent need to develop some effective treatment. Currently, only 2 classes of drugs are available for AD treatment namely acetylcholinesterase inhibitor and NMDA receptor antagonist. Since AD is a complex neurological disorder and these drugs use a single target approach, alternatives are needed due to limited effectiveness and unpleasant side-effects of these drugs. Currently, plants have been used for drug development research especially because of their multiple sites of action and fewer side effects. Uses of some herbs and phytoconstituents for the management of neuronal disorders like AD have been documented in this article. Phytochemical screening of these plants shows the presence of many beneficial constituents like flavonoids, triterpenes, alkaloids, sterols, polyphenols, and tannins. These compounds show a wide array of pharmacological activities such as anti-amyloidogenic, anticholinesterase, and antioxidant. This article summarizes the present understanding of AD progression and gathers biochemical evidence from various works on natural products that can be useful in the management of this disease.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Latent Variable ◽  
Brain Regions ◽  
Disease Assessment ◽  
Latent Variable Analysis ◽  
The Relationship ◽  
Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

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