How Can We Improve Transfer of Outcomes from Randomized Clinical Trials to Clinical Practice with Disease-Modifying Drugs in Alzheimer's Disease?

2013 ◽  
Vol 13 (2-3) ◽  
pp. 197-199 ◽  
Author(s):  
S. Gauthier ◽  
A. Leuzy ◽  
P. Rosa-Neto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Randomized Clinical Trials ◽  
Disease Modifying Drugs ◽  
Disease Modifying

scholarly journals New Approacher in the Development of Alzheimer’s Disease Modifying Drugs

2021 ◽  
pp. 88
Author(s):  
◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Tau Protein ◽  
Phase Iii ◽  
Disease Modifying Drugs ◽  
Phase Iii Clinical Trials ◽  
Research Level ◽  
Disease Modifying ◽  
Pathological Stages

Introduction: Alzheimer’s disease is a more common neurodegenerative disease, affecting 25 million people worldwide, or accounting for about 60 to 70% of all dementia cases. There is currently no exact mechanism to explain the pathophysiology of Alzheimer’s disease, however, cascading metabolic amyloid and post-translational review of tau protein are used as major hypotheses. Objective: To demonstrate in the literature new approaches in the development of Alzheimer’s disease modifiers. Methodology: For the accomplishment of this study made in the bibliographical survey of scientific literature and respect to the approached subject, in the databases PUBMED, ScienceDirect, Scielo and Scopus. Results: Alzheimer’s disease-modifying drugs are not yet available, but many patients may, however, develop phase III clinical trials and are intended to modify as pathological stages leading to the disease. As disease-modifying therapies under study, these changes also affect Aβ and tau protein and also cause inflammation and oxidative damage. The results obtained in the clinical trials performed were positive and promising and are still under study. The results show that there is still a long way to go in the development of Alzheimer’s disease modifying drugs. Conclusion: The results demonstrated that there is still a long way to go in the development of Alzheimer’s disease modifying drugs, but nevertheless levels at the research level should be continued in order to improve the pathophysiology of the disease and find an effective treatment for this disease the same.

scholarly journals Regulatory and Health Technology Assessment Considerations for Disease-Modifying Drugs in Alzheimer’s Disease

CNS Drugs ◽  
2018 ◽  
Vol 32 (12) ◽  
pp. 1085-1090 ◽  
Author(s):  
Jacoline C. Bouvy ◽  
Pall Jonsson ◽  
Diana O’Rourke ◽  
Antonella Santuccione Chadha ◽  
Niklas Hedberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology ◽  
Disease Modifying Drugs ◽  
Disease Modifying

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.

Does protein aggregation drive postmitotic tissue degeneration?

2021 ◽  
Vol 13 (577) ◽  
pp. eaax0914 ◽  
Author(s):  
Jeffery W. Kelly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Protein Aggregation ◽  
Protein Aggregate ◽  
Tissue Degeneration ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
Amyloid Diseases ◽  
Aggregate Structures

Pharmacological evidence, from clinical trials where patients with systemic amyloid diseases are treated with disease-modifying therapies, supports the notion that protein aggregation drives tissue degeneration in these disorders. The protein aggregate structures driving tissue pathology and the commonalities in etiology between these diseases and Alzheimer’s disease are under investigation.

REPORT FROM THE FIRST CLINICAL TRIALS ON ALZHEIMER’S DISEASE (CTAD) ASIA-CHINA 2018 : BRINGING TOGETHER GLOBAL LEADERS

2019 ◽  
pp. 1-4
Author(s):  
J.K. Chhetri ◽  
P. Chan ◽  
B. Vellas ◽  
J. Touchon ◽  
S. Gauthier
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Chinese Population ◽  
The West ◽  
Disease Modifying Therapies ◽  
Increased Risk ◽  
Disease Modifying ◽  
Past Experiences

Population of older adults in Asia, and particularly in China is increasing rapidly. Older population are at increased risk of Alzheimer’s disease (AD) and other dementias. Soon, the Chinese population with AD will represent almost half of the world’s AD population. There is a desperate need of disease modifying therapies to delay or slow the progression of AD, to tackle this emerging healthcare emergency. In this context, the first CTAD Asia-China conference was held in China to bring together Western and Asian leaders in AD. This meeting focused largely on how to develop successful trials in China, utilizing past experiences from the West.

Simulating the Effects of Common Comedications and Genotypes on Alzheimer’s Cognitive Trajectory Using a Quantitative Systems Pharmacology Approach

2020 ◽  
Vol 78 (1) ◽  
pp. 413-424
Author(s):  
Hugo Geerts ◽  
Athan Spiros
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Second Generation ◽  
Standard Of Care ◽  
Systems Pharmacology ◽  
Quantitative Systems Pharmacology ◽  
Pharmacodynamic Interactions ◽  
Cognitive Trajectory

Background: Many Alzheimer’s disease patients in clinical practice are on polypharmacy for treatment of comorbidities. Objective: While pharmacokinetic interactions between drugs have been relatively well established with corresponding treatment guidelines, many medications and common genotype variants also affect central brain circuits involved in cognitive trajectory, leading to complex pharmacodynamic interactions and a large variability in clinical trials. Methods: We applied a mechanism-based and ADAS-Cog calibrated Quantitative Systems Pharmacology biophysical model of neuronal circuits relevant for cognition in Alzheimer’s disease, to standard-of-care cholinergic therapy with COMTVal158Met, 5-HTTLPR rs25531, and APOE genotypes and with benzodiazepines, antidepressants, and antipsychotics, all together 9,585 combinations. Results: The model predicts a variability of up to 14 points on ADAS-Cog at baseline (COMTVV 5-HTTLPRss APOE 4/4 combination is worst) and a four-fold range for the rate of progression. The progression rate is inversely proportional to baseline ADAS-Cog. Antidepressants, benzodiazepines, first-generation more than second generation, and most antipsychotics with the exception of aripiprazole worsen the outcome when added to standard-of-care in mild cases. Low dose second-generation benzodiazepines revert the negative effects of risperidone and olanzapine, but only in mild stages. Non APOE4 carriers with a COMTMM and 5HTTLPRLL are predicted to have the best cognitive performance at baseline but deteriorate somewhat faster over time. However, this effect is significantly modulated by comedications. Conclusion: Once these simulations are validated, the platform can in principle provide optimal treatment guidance in clinical practice at an individual patient level, identify negative pharmacodynamic interactions with novel targets and address protocol amendments in clinical trials.

Dance for People with Alzheimer’s Disease: A Systematic Review

2019 ◽  
Vol 16 (10) ◽  
pp. 919-933 ◽  
Author(s):  
Alicia Ruiz-Muelle ◽  
María Mar López-Rodríguez
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Function ◽  
Dance Therapy ◽  
Randomized Clinical Trials ◽  
Future Research

Background: In recent years, several reviews have addressed the effectiveness of dance therapy in dementia, healthy older adults, or the elderly in general. However, reviews regarding the effect of this therapy exclusively on patients diagnosed with Alzheimer’s disease have not been found. Objective: The purpose of this study is to review the available literature describing clinical trials which explore the effects of dancing on psychological and physical outcomes, functionality, cognitive function, and quality of life in patients diagnosed with Alzheimer’s disease. In addition, this review aims to assess the quality of studies that perform dance therapy interventions in these patients. Methods: This study is a systematic review of randomized and non-randomized clinical trials regarding the effect of intervention including a dancing activity in people diagnosed with Alzheimer's disease. Results: In total, the evidence for this review rests on 12 studies with a total of 349 participants. The findings of this mini-review confirm the positive effect of dance therapy on physical and cognitive function, functionality, psychological outcomes, and quality of life in people with Alzheimer's disease. Conclusion: Most of the studies implementing dance as part of the therapeutic treatment has shown to improve or slow the worsening in the quality of life of patients with Alzheimer's disease and their caregivers. Future research focused on these patients should use a more exhaustive methodology and make a more detailed description of these kind of interventions.

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