scholarly journals Defeating dementia: Current approaches to potential amyloid-based Alzheimer's disease therapies

2008 ◽  
Vol 30 (5) ◽  
pp. 14-17 ◽  
Author(s):  
Ayesha Khan ◽  
Clive Ballard
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Receptor Antagonist ◽  
Disease Progression ◽  
Cholinesterase Inhibitors ◽  
Neurodegenerative Disorder ◽  
The Uk

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, accounting for 700000 people in the UK and 25 million people worldwide with dementia1. Already licensed treatments, cholinesterase inhibitors and an NMDA (Nmethyldaspartate) receptor antagonist, confer important symptomatic benefits2, but at present, there are no treatments that can delay or halt the disease progression. This review outlines one of the main mechanisms currently thought to underpin the development of AD, and the treatments that are being developed based upon it.

scholarly journals Alzheimer’s Disease: Current and Future Treatments. A Review

2014 ◽  
Vol 2 (2) ◽  
pp. 56-63
Author(s):  
Evelyn Chou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Neurodegenerative Disorder ◽  
Nmda Antagonists ◽  
Disease Modifying Drugs ◽  
Plaque Deposition ◽  
The Future ◽  
Disease Modifying ◽  
Future Treatments

Alzheimer’s disease (AD) is a currently incurable neurodegenerative disorder whose treatment poses a big challenge. Proposed causes of AD include the cholinergic, amyloid and tau hypotheses. Current therapeutic treatments have been aimed at dealing with the neurotransmitter imbalance. These include cholinesterase inhibitors and N-Methyl-D-aspartate (NMDA) antagonists. However, current therapeutics have been unable to halt AD progression. Much research has gone into the development of disease-modifying drugs to interfere with the course of the disease. Approaches include secretase inhibition and immunotherapy aimed at reducing plaque deposition. However, these have not been successful in curing AD as yet. It is believed that the main reason why therapeutics have failed to work is that treatment begins too late in the course of the disease. The future of AD treatment thus appears to lie with prevention rather than cure. In this article, current therapeutics and, from there, the future of AD treatment are discussed.

scholarly journals Combination Therapy in Moderate to Severe Alzheimer’s Disease - Overview and Discussion Points for the Future

2011 ◽  
Vol 6 (4) ◽  
pp. 228
Author(s):  
José L Molinuevo ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Combination Therapy ◽  
Receptor Antagonist ◽  
Cholinesterase Inhibitors ◽  
Current Data ◽  
Aspartate Receptor ◽  
The Future

Two effective symptomatic therapies are available for Alzheimer’s disease: the cholinesterase inhibitors (ChEIs) and memantine, an N-methyl-D-aspartate receptor antagonist. Current data demonstrate that combination therapy with memantine and a ChEI produces symptomatic benefits in all domains of AD. The benefits of combination therapy are greater than those of ChEI monotherapy, are sustained long term and appear to increase with time.

Physicians' Efficacy Requirements for Prescribing Medications to Persons with Alzheimer's Disease

2007 ◽  
Vol 26 (2) ◽  
pp. 139-148 ◽  
Author(s):  
Mark Oremus ◽  
Christina Wolfson ◽  
Howard Bergman ◽  
Alain C Vandal
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Odds Ratio ◽  
Daily Living ◽  
Cholinesterase Inhibitors ◽  
Postal Survey ◽  
Drug Treatments ◽  
Efficacy Measures ◽  
Cent Level

ABSTRACTPhysicians (N = 803) were contacted via postal survey and given two sets of efficacy measures for drug treatments in Alzheimer's disease: (a) the time that patients spend in a mild or moderate state of disease; (b) levels of modification to disease progression in the areas of cognition, behaviour, and mood, and ability to perform basic activities of daily living. Physicians reported that they would prescribe a hypothetical, new Alzheimer's disease medication if it would allow patients to remain in their current disease state for 15 (mild) or 11 (moderate) additional months. Most physicians required a permanent halt to, or some reversal of, disease progression as a prerequisite for prescribing; a few required substantial reversal. More stringent efficacy requirements were negatively associated with physicians' current prescribing of cholinesterase inhibitors to persons with Alzheimer's disease, although the effects were either small (odds ratio = 0.99) or not statistically significant at the 5 per cent level. The results suggest that physicians with stringent efficacy requirements for clinically relevant efficacy measures are less likely to prescribe cholinesterase inhibitors.

A Systematic Review on Donepezil-based Derivatives as Potential Cholinesterase Inhibitors for Alzheimer’s Disease

2019 ◽  
Vol 26 (30) ◽  
pp. 5625-5648 ◽  
Author(s):  
Jan Korabecny ◽  
Katarina Spilovska ◽  
Eva Mezeiova ◽  
Ondrej Benek ◽  
Radomir Juza ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Nmda Receptor Antagonist ◽  
Amyloid Burden ◽  
Ache Inhibitors ◽  
Intellectual Capacity ◽  
Β Amyloid

: Alzheimer’s Disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine. Donepezil was able to ameliorate the symptoms related to AD mainly via AChE, but also through reduction of β-amyloid burden. This review presents the overview of donepezilrelated compounds as potential anti-AD drugs developed on the basis of cholinergic hypothesis to act as solely AChE and butyrylcholinesterase (BChE) inhibitors.

scholarly journals Non-Alkaloid Cholinesterase Inhibitory Compounds from Natural Sources

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5582
Author(s):  
Alfred Ngenge Tamfu ◽  
Selcuk Kucukaydin ◽  
Balakyz Yeskaliyeva ◽  
Mehmet Ozturk ◽  
Rodica Mihaela Dinica
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
High Efficiency ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
New Drugs ◽  
Cholinesterase Inhibition ◽  
Natural Sources ◽  
Long Term Treatment

Alzheimer’s disease (AD) is a severe neurodegenerative disorder of different brain regions accompanied by distresses and affecting more than 25 million people in the world. This progressive brain deterioration affects the central nervous system and has negative impacts on a patient’s daily activities such as memory impairment. The most important challenge concerning AD is the development of new drugs for long-term treatment or prevention, with lesser side effects and greater efficiency as cholinesterases inhibitors and the ability to remove amyloid-beta(Aβ) deposits and other related AD neuropathologies. Natural sources provide promising alternatives to synthetic cholinesterase inhibitors and many have been reported for alkaloids while neglecting other classes with potential cholinesterase inhibition. This review summarizes information about the therapeutic potential of small natural molecules from medicinal herbs, belonging to terpenoids, coumarins, and phenolic compounds, and others, which have gained special attention due to their specific modes of action and their advantages of low toxicity and high efficiency in the treatment of AD. Some show superior drug-like features in comparison to synthetic cholinesterase inhibitors. We expect that the listed phytoconstituents in this review will serve as promising tools and chemical scaffolds for the discovery of new potent therapeutic leads for the amelioration and treatment of Alzheimer’s disease.

Alzheimer's Disease: A Review from the Pathophysiology to Diagnosis, New Perspectives for Pharmacological Treatment

2018 ◽  
Vol 25 (26) ◽  
pp. 3141-3159 ◽  
Author(s):  
Leide Caroline dos Santos Picanco ◽  
Priscilla F. Ozela ◽  
Maiara de Fatima de Brito Brito ◽  
Abraao A. Pinheiro ◽  
Elias C. Padilha ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Functions ◽  
Cholinesterase Inhibitors ◽  
Neurodegenerative Disorder ◽  
Glycogen Synthase ◽  
New Therapeutic Approaches ◽  
Cerebrospinal Fluid Biomarkers ◽  
Microscopic Features ◽  
And Behavior

Dementia is characterized by the impairment of cognition and behavior of people over 65 years. Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the world, as approximately 47 million people are affected by this disease and the tendency is that this number will increase to 62% by 2030. Two microscopic features assist in the characterization of the disease, the amyloid plaques and neurofibrillary agglomerates. All these factors are responsible for the slow and gradual deterioration of memory that affect language, personality or cognitive control. For the AD diagnosis, neuropsychological tests are performed in different spheres of cognitive functions but since not all cognitive functions may be affected, cerebrospinal fluid biomarkers are used along with these tests. To date, cholinesterase inhibitors are used as treatment, they are the only drugs that have shown significant improvements in the cognitive functions of AD patients. Despite the proven effectiveness of cholinesterase inhibitors, an AD carrier, even while being treated, is continually subjected to progressive degeneration of the neuronal tissue. For this reason, other biochemical pathways associated with the pathophysiology of AD have been explored as alternatives to the treatment of this condition such as inhibition of β-secretase and glycogen synthase kinase-3β. The present study aims to conduct a review of the epidemiology, pathophysiology, symptoms, diagnosis and treatment of Alzheimer's disease, emphasizing the research and development of new therapeutic approaches.

scholarly journals Comparative Gene-Expression Analysis of Alzheimer’s Disease Progression with Aging in Transgenic Mouse Model

2019 ◽  
Vol 20 (5) ◽  
pp. 1219 ◽  
Author(s):  
Noman Abid ◽  
Muhammad Naseer ◽  
Myeong Kim
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Disease Progression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Neurodegenerative Disorder ◽  
Age Groups ◽  
Analysis Tool

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive memory dysfunction and a decline in cognition. One of the biggest challenges to study the pathological process at a molecular level is that there is no simple, cost-effective, and comprehensive gene-expression analysis tool. The present study provides the most detailed (Reverse transcription polymerase chain reaction) RT-PCR-based gene-expression assay, encompassing important genes, based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) disease pathway. This study analyzed age-dependent disease progression by focusing on pathological events such as the processing of the amyloid precursor protein, tau pathology, mitochondrial dysfunction, endoplasmic reticulum stress, disrupted calcium signaling, inflammation, and apoptosis. Messenger RNA was extracted from the cortex and hippocampal region of APP/PS1 transgenic mice. Samples were divided into three age groups, six-, nine-, and 12-month-old transgenic mice, and they were compared with normal C57BL/6J mice of respective age groups. Findings of this study provide the opportunity to design a simple, effective, and accurate clinical analysis tool that can not only provide deeper insight into the disease, but also act as a clinical diagnostic tool for its better diagnosis.

scholarly journals Alzheimer’s Disease Pharmacotherapy in Relation to Cholinergic System Involvement

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 40 ◽  
Author(s):  
Gabriela Dumitrita Stanciu ◽  
Andrei Luca ◽  
Razvan Nicolae Rusu ◽  
Veronica Bild ◽  
Sorin Ioan Beschea Chiriac ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Global Health ◽  
Disease Progression ◽  
Cholinergic System ◽  
Cholinesterase Inhibitors ◽  
Current Understanding ◽  
Brain Functioning ◽  
System Involvement ◽  
Global Health Challenge

Alzheimer’s disease, a major and increasing global health challenge, is an irreversible, progressive form of dementia, associated with an ongoing decline of brain functioning. The etiology of this disease is not completely understood, and no safe and effective anti-Alzheimer’s disease drug to prevent, stop, or reverse its evolution is currently available. Current pharmacotherapy concentrated on drugs that aimed to improve the cerebral acetylcholine levels by facilitating cholinergic neurotransmission through inhibiting cholinesterase. These compounds, recognized as cholinesterase inhibitors, offer a viable target across key sign domains of Alzheimer’s disease, but have a modest influence on improving the progression of this condition. In this paper, we sought to highlight the current understanding of the cholinergic system involvement in Alzheimer’s disease progression in relation to the recent status of the available cholinesterase inhibitors as effective therapeutics.

scholarly journals Use of cholinesterase inhibitors in dementia

2002 ◽  
Vol 8 (2) ◽  
pp. 89-96 ◽  
Author(s):  
Mark Holden ◽  
Cornelius Kelly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Older People ◽  
Annual Cost ◽  
Cholinesterase Inhibitors ◽  
Dementia Care ◽  
Burden Of Care ◽  
Common Cause ◽  
Audit Commission ◽  
The Uk

Alzheimer's disease is the most common cause of dementia in older people, with about half a million people affected in the UK. Its effects are devastating and far-reaching for sufferers, their carers and society in general – the Audit Commission estimated the annual cost of dementia care for 1998–1999 at £6.1 billion (Audit Commission, 2000). There is no cure and it is terminal within 3 to 7 years of diagnosis. Given an estimated doubling of dementia cases over the next 50 years (Melzer et al, 1997), the burden of care is set to increase substantially.

scholarly journals Imaging Techniques in Alzheimer’s Disease: A Review of Applications in Early Diagnosis and Longitudinal Monitoring

2021 ◽  
Vol 22 (4) ◽  
pp. 2110
Author(s):  
Wieke M. van Oostveen ◽  
Elizabeth C. M. de Lange
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Disease Progression ◽  
Neurodegenerative Disorder ◽  
Imaging Techniques ◽  
Disease Onset ◽  
Amyloid Β ◽  
Multiple Imaging ◽  
Novel Biomarkers

Background. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting many individuals worldwide with no effective treatment to date. AD is characterized by the formation of senile plaques and neurofibrillary tangles, followed by neurodegeneration, which leads to cognitive decline and eventually death. Introduction. In AD, pathological changes occur many years before disease onset. Since disease-modifying therapies may be the most beneficial in the early stages of AD, biomarkers for the early diagnosis and longitudinal monitoring of disease progression are essential. Multiple imaging techniques with associated biomarkers are used to identify and monitor AD. Aim. In this review, we discuss the contemporary early diagnosis and longitudinal monitoring of AD with imaging techniques regarding their diagnostic utility, benefits and limitations. Additionally, novel techniques, applications and biomarkers for AD research are assessed. Findings. Reduced hippocampal volume is a biomarker for neurodegeneration, but atrophy is not an AD-specific measure. Hypometabolism in temporoparietal regions is seen as a biomarker for AD. However, glucose uptake reflects astrocyte function rather than neuronal function. Amyloid-β (Aβ) is the earliest hallmark of AD and can be measured with positron emission tomography (PET), but Aβ accumulation stagnates as disease progresses. Therefore, Aβ may not be a suitable biomarker for monitoring disease progression. The measurement of tau accumulation with PET radiotracers exhibited promising results in both early diagnosis and longitudinal monitoring, but large-scale validation of these radiotracers is required. The implementation of new processing techniques, applications of other imaging techniques and novel biomarkers can contribute to understanding AD and finding a cure. Conclusions. Several biomarkers are proposed for the early diagnosis and longitudinal monitoring of AD with imaging techniques, but all these biomarkers have their limitations regarding specificity, reliability and sensitivity. Future perspectives. Future research should focus on expanding the employment of imaging techniques and identifying novel biomarkers that reflect AD pathology in the earliest stages.

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