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).

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.

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.

scholarly journals Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease

2006 ◽  
Vol 12 (5) ◽  
pp. 707-735 ◽  
Author(s):  
ELIZABETH W. TWAMLEY ◽  
SUSAN A. LEGENDRE ROPACKI ◽  
MARK W. BONDI
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Functional Neuroimaging ◽  
Neuropsychological Functioning ◽  
Clinical Manifestations ◽  
Symptomatic Treatment ◽  
Cross Sectional ◽  
Preclinical Ad ◽  
Normal Individuals

Alzheimer's disease (AD) is a common, devastating form of dementia. With the advent of promising symptomatic treatment, the importance of recognizing AD at its very earliest stages has increased. We review the extant neuropsychological and neuroimaging literature on preclinical AD, focusing on longitudinal studies of initially nondemented individuals and cross-sectional investigations comparing at-risk with normal individuals. We systematically reviewed 91 studies of neuropsychological functioning, structural neuroimaging, or functional neuroimaging in preclinical AD. The neuropsychological studies indicated that preclinical AD might be characterized by subtle deficits in a broad range of neuropsychological domains, particularly in attention, learning and memory, executive functioning, processing speed, and language. Recent findings from neuroimaging research suggest that volume loss and cerebral blood flow or metabolic changes, particularly in the temporal lobe, may be detected before the onset of dementia. There exist several markers of a preclinical period of AD, in which specific cognitive and biochemical changes precede the clinical manifestations. The preclinical indicators of AD reflect early compromise of generalized brain integrity and temporal lobe functioning in particular. (JINS, 2006,12, 707–735.)

scholarly journals The Importance of Group-Wise Registration in Tract Based Spatial Statistics Study of Neurodegeneration: A Simulation Study in Alzheimer's Disease

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e45996 ◽  
Author(s):  
Shiva Keihaninejad ◽  
Natalie S. Ryan ◽  
Ian B. Malone ◽  
Marc Modat ◽  
David Cash ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Statistics ◽  
Simulation Study ◽  
Tract Based Spatial Statistics

scholarly journals The Impact of a Long-Term Rivastigmine and Donepezil Treatment on All-Cause Mortality in Patients With Alzheimer’s Disease

2018 ◽  
Vol 33 (6) ◽  
pp. 385-393 ◽  
Author(s):  
Jakub Kazmierski ◽  
Chaido Messini-Zachou ◽  
Mara Gkioka ◽  
Magda Tsolaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cox Regression ◽  
Symptomatic Treatment ◽  
Risk Of Death ◽  
Increased Risk ◽  
Functional Assessments ◽  
The Impact

Cholinesterase inhibitors (ChEIs) are the mainstays of symptomatic treatment of Alzheimer’s disease (AD); however, their efficacy is limited, and their use was associated with deaths in some groups of patients. The aim of the current study was to assess the impact of the long-term use of ChEIs on mortality in patients with AD. This observational, longitudinal study included 1171 adult patients with a diagnosis of AD treated with donepezil or rivastigmine. Each patient was observed for 24 months or until death. The cognitive and functional assessments, the use of ChEIs, memantine, antipsychotics, antidepressants, and anxiolytics were recorded. The total number of deaths at the end of the observational period was 99 (8.45%). The patients who had received rivastigmine treatment were at an increased risk of death in the follow-up period. The higher risk of death in the rivastigmine group remained significant in multivariate Cox regression models.

Sign in / Sign up

Export Citation Format

Share Document