Posted: August 18th, 2015

Does the combination of Donepezil and memantine alleviate behavioral symptoms and slow down cognitive decline in Alzheimer’s disease Patients without compromising their tolerability?

Does the combination of Donepezil and memantine alleviate behavioral symptoms and slow down cognitive decline in Alzheimer’s disease Patients without compromising their tolerability?

NURS 3046 Nursing ProjectAssignment 1 (2000 words 45%)
STUDENT NAME:     STUDENT ID:

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Please note: this assignment is 2,000 words so only that word count will be marked. The 2,000 word count includes in-test references but excludes the Reference List.

Background (300approx)
State yourresearch question and provide background and rationale about why you developed the question. Explain how your research question is important and relevant (useful) for the development of clinical practice or professional knowledge at a local and/or international level.

Alzheimer’s disease is a common neurodegenerative disorder that affects and causes the loss of cognitive faculties denying the affected patients the ability to effectively perform their activities of daily living (Doraiswamy et al. 2008). It is presently the most prevalent form of adult onset dementia and the affected patients usually experience both neuropsychiatric and behavioral difficulties. Although there is presently no specific cure for Alzheimer’s disease, the cholinergic and glutamatergic system treatments have been found to alleviate the cognitive and behavioral symptoms to a great extent (Doraiswamy et al. 2008). The acetyl cholinesterase/cholinesterase inhibitors usually elevate the levels of the acetylcholine and this is achieved breaking down the neurotransmitters. On the other hand, memantine acts by antagonizing the N-methyl-D-aspartate receptors, thus alleviating the patient’s behavioral symptoms (Tariot et al. 2005).
Research Question – Does the combination of Donepezil and memantine alleviate behavioral symptoms and slow down cognitive decline in Alzheimer’s disease Patients without compromising their tolerability?
Since there is no particular treatment that has been developed to completely cure or modify the disease, the attention of all medical professionals and researchers has been focused on alleviating the symptoms, minimizing their progression and at the same time ensuring that the underlying pathophysiology is not modified. More resources and time should therefore be invested towards achieving these treatment goals since their achievement gives patients the opportunity to stay for a longer period of time on the more functional milder stages of the disease. Although alleviating disease symptoms and reducing their clinical worsening is very beneficial in improving the quality of life of Alzheimer’s disease patients, their safety is equally important thus the rationale of focusing on the safety and tolerability of the combination treatment as well.

Summarise Four Primary Research Articles(1000 words)
Write a summary paragraph of your 4 research articles using the five step format you learned in Week 2.

Paper 1
Arti, A, Molinuevo, JL, Lemming, O, Wirth, Y, Pulte & Wilkinson, D 2013, ‘Memantine in patients with Alzheimer’s disease receiving donepezil: new analyses of efficacy and safety for combination therapy’,  Alzheimer’s Research & Therapy, vol. 5, no. 6, pp. 2-11.
In this article, Arti and his colleagues were trying to analyze and determine the safety and efficiency of using mamentine on Alzheimer’s disease patients who are already under donepezil treatment therapy. Cholinesterase when used in combination with memantine has been found by various studies to be very beneficial in alleviating behavioral and cognitive symptoms in Alzheimer’s disease patients and therefore this study strives to analyze efficacy and safety of using them in combination and particularly where by the memantine is introduced to stable donepezil. The study was carried out on patients in the moderate to severe stages of the disease. The authors established and confirmed the claims made by previous works of research that adding memantine to stable donepezil in a combination treatment for Alzheimer’s disease patients significantly promotes the reduction of function, cognition and global status decline. Furthermore, they concluded that the combination treatment is safe and tolerable in addition, the extent of the effects was found to be great enough to have both statistical and clinical significance. Since this study involved patients from the stages of the disease that accommodate the largest number of patients, its findings are reliable to a great extent. Moreover, the data was collected over a period of 24 weeks, giving sufficient time to study and determine whether the patients’ health status was deteriorating or improving, the findings are most likely to be true and therefore are reliable and useful in my research. This article therefore meets the needs of this assignment and will be a very useful resource in answering my research question.

Paper 2
Farrimond, LE, Roberts, E & McShane, R 2012, ‘Memantine and cholinesterase inhibitor combination therapy for Alzheimer’s disease: a systemic review’, BMJ Open, vol. 2, no. 3, pp. 917-923.
This article strives to examine the comparison in the efficacy between the use of cholinesterase monotherapy for the treatment of Alzheimer’s disease and its use in combination with memantine for the treatment and management of the same. The authors further examine what impacts using unpublished data in their findings would have on their final results. The study was carried out on patients in the moderate to severe stages of Alzheimer’s disease. Combination therapy of memantine and cholinesterase has been widely suggested to be efficient in the alleviation of Alzheimer’s disease symptoms. However, in this article, the authors suggest that the benefits of using the combination therapy are very minimal at six months and that there was no effect on patients functions whatsoever. Therefore, the study does not demonstrate sufficient clinical relevance of the effects of the combination therapy. Throughout their investigation, Farrimond and his friends demonstrate the view point that even at one year; the combination therapy does not show any superiority over monotherapy on moderate to severe Alzheimer’s disease. This article lacks reliable evidence to support its claims and therefore may not be very useful in answering the research question in this assignment. Furthermore, it does not discuss the issue of safety and tolerability of the combination therapy, which are key factors in the research question. However, this article may be containing useful information for the analysis of the comparison between the use of monotherapy and combination therapy in Ads management although it will require some additional research and adaptation in order to qualify to be used in this assignment.

Paper 3
Molino, I, Colucci, L, Fasanaro, A, Traini, E & Amenta, F 2013, ‘Efficacy of memantine, Donepezil, or their association in moderate to severe Alzheimer’s disease: A review of clinical trials’, The Scientific World Journal, vol. 2013, pp. 1-8.
This article focuses on reviewing and analyzing the effectiveness of using either memantine or donepezil for the management of Alzheimer’s disease symptoms, in comparison with the use of the two in combination for the same purpose. The study relies on the review of past evidence from different clinical trials and focuses on moderate to severe Alzheimer’s disease patients. Both memantine and donepezil have been licensed for the alleviation of AD symptoms in most countries including the US, and their combination therapy has been strongly proposed, stirring mixed opinions concerning its effectiveness and safety. Therefore the authors of article seek to establish whether it’s more effective to use the drugs in combination or independently. From their research, the authors found that both memantine and donepezil were effective in improving the symptoms of Alzheimer’s disease especially among moderate to severe patients. However, on their opinion, they did not find sufficient evidence to support the benefits of using them in combination. Furthermore, the study confirmed the safety and tolerability of donepezil on moderate and severe cases of Alzheimer’s disease, but does not support or provide sufficient evidence on the safety and tolerability of either memantine or its combination with donepezil. The most significant limitation of this study is the employment of various cognitive assessment tools that could not facilitate proper comparison of the different trials. However, it contains different viewpoints of different researchers and therefore will be useful in answering the research question in this assignment to a great extent.

Paper 4
Mayer, M & Pulte, I 2013, ‘How safe is combination memantine/donepezil treatment in people with Alzheimer’s disease? Safety evaluation based on 23 clinical studies’, The Journal of the Alzheimer’s Association, vol. 9, no. 4, p. 282.
In this article, Mayer and Pulte’s purpose of study was to investigate the level of safety of using a combination of memantine and donepezil treatments in the management of Alzheimer’s disease. Donepezil has been widely used in many parts of the world in combination with memantine for Alzheimer’s disease patients and therefore the main concern of these authors was the safety of this combination on the patients. The study was based on review of data obtained from different clinical researches. Finally, the results obtained from this study lead to the conclusion that the combination of memantine and donepezil is safe and does not compromise the overall health of Alzheimer’s disease patients. In addition, the combination was found to be well tolerable by patients, whether used on short term or long-term basis. This article is therefore very useful in answering my research question since it draws its evidence from many clinical studies and concentrates on establishing the safety of the combination therapy, which is the core of this assignment.

Discussion (550 approx)
Compare and contrast the findings of each research paper. Ensure that your analysis explains why your research papers are relevant andhow the quality of the findings enables the stated research question to be answered. Identify any existing gaps in knowledge or practice. Discussion should be supported by additional relevant literature.

It is evident from majority of the studies that memantine and donepezil combination therapy is more effective in the alleviation of Alzheimer’s disease symptoms that each of the drugs used independent. Most of the articles used in this research support this claim and their findings are very viable in the effort to answer the research question. However, they demonstrate some differences mainly in the research methods employed and thus the cause for the variations in their conclusions. The study samples in all the studies are similar as the authors used patients in the moderate to severe stages of Alzheimer’s disease. This makes them very reliable because these stages have the largest population of Alzheimer’s disease patients. The authors ensured that the patient’s population was we’ll represent. The methodology applied varied from one study to the other. For instance in paper 1, the authors relied on analysing first hand data collected from the clinical trials carried out over a period of 24 weeks. In addition, they used cognition, function and global status measures to assess the efficacy of the combined therapy and this led them to the conclusion that the combined treatment is actually more efficient than a single treatment. Similarly, the authors of the second article applied a systematic review and metaanalysis of randomized controlled trials on patients in the same stages of AD as the first paper. However, their findings were different since they observed very minimal difference between the monotherapy and combined treatment. Although this article does not support the research question, it is very useful as it gives a different t opinion on the subject, prompting further research. The third article adopts a different methology as the authors rely on the review of past researches but its findings support the research question. The outcome of the forth research also supports the claim that combined treatment gives a better outcome that monotherapy. The two drugs have different mechanisms of action and this explains the improvement in effectiveness observed from the combination therapy. The two drugs have different effects on different transmitter systems, with memantine mainly targeting natural neurotransmitters while donepezil selectively inhibits acetylcholinesterace (Tariot et al. 2005). Moreover, the combination therapy improves the patient’s quality of life, enabling them to sustain autonomy for a considerable period of time. In addition, various studies have revealed that the safety and tolerability of the combination therapy is higher than the use of donepezil alone. Tariot et al. (2005) observed that using the two drugs together reduces the occurrence of such side effects as diarrhoea and faecalincontinence as well as constipation which are common in the independent use of either memantine or donepezil.

Conclusion (150 approx)
Summarize the major points in a synthesized non-repetitive manner, clear future directions for research.

Alzheimer’s disease is one of the most common adult onset progressive mental disorders and has serious adverse effects on the affected patient’s higher cortical functions. It usually affects a person’s thinking memory, comprehension and orientation capacity thus affecting their day to day activities. The management of Alzheimer’s disease demands relatively high financial and emotional investment on the affected families and the society at large. This is because AD patients require very close attention, and sometimes calling for hospitalization especially when the disease advances to severe levels. Although the established treatment options for this disease do not guarantee complete cure, they go a long way in alleviating its symptoms as well as delaying disease progression thus improving the patient’s quality of life. Memantine and donepezil are the most widely licensed treatment options and have been found to significantly improve the condition. However, their use in combination has attracted a lot of attention lately, and various medical studies have found it to be more effective than when used individually. However, the question of safety and tolerability of this combination therapy has attracted mixed opinions with majority of studies guaranteeing its safety and tolerability.

Word count: 2050

References
Use correct UniSA Harvard Referencing

Doraiswamy, PM, Gwylther, LP & Adler, T 2008, ‘The Alzheimer’s action plan’, in T Adler (ed.), The experts’ guide to the best diagnosis and treatment for memory problems, St. Martin’s Press, New York, pp. 235-246.

Tariot, PN, Farlow, MR, Grossberg, GT, Graham, SM, Mcdonald, S & Gergel, I 2005, ‘Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial’, JAMA, vol. 291, no.3, pp. 317-324.

NURS 3046  Nursing ProjectAssessment Feedback Form
Assignment 1 Weighting 45% of final grade (2000 words)Course Objectives assessed: 1; 2; 3
Criteria     HD(85% -100%)    D (75% – 84%)    C(65% – 74%)    P1 (55% – 64%)    P2(50% – 54%)    F1(40% – 49%)    F2(39% – 0%)

Background

(300 words)

10 marks
Includes all requirements of DNANDexceptional description of background;how research question is relevant for clinical practice or professional knowledge. Evidence of original thought.     Includes all requirements of a CreditANDprovidescomprehensive criticalrationale about how the stated research question is highlyimportant and broadlyrelevant for the development of clinical practice or professional knowledgeat a local and/or international level.     Includes allrequirements of a P1AND provides a thorough, more advanced rationale about how the stated research questionis important and relevant for the development of clinical practice or professional knowledgeat a local and/or international level.     Research question adequately stated, clearbackground provided.

Rationale presented to explain how the research question is important and relevant(useful)for the development of clinical practice or professional knowledge at a local and/or international level.
Research issue stated, but not formulated into a question
Limitedattempt to provide background information on the relevance of the question.

Basic/weak rationale about importance of the question for the development of clinical practice or professional knowledge at a local and/or international level.    Does not clearly identify research issue, question or background;

Question stated but inadequateand/or irrelevantexplanation of importance for clinical practice.
Purpose is vague
incorrect
As for FIANDResearch question
missing

Poorly described and/or incoherent background description

Summary of four Research Papers

(250 words per research paper)

40 marks

Includes all requirements of a Distinction ANDdemonstrates exemplary critical analysis ofresearch articles, synthesis of information and original thought.

Demonstrated an exceptional understanding of each paper linked clearly to the stated research question.

Includes all requirements of a Credit AND
provides a high level comprehensive critical analysis the research articles, demonstratingin-depth, comprehensive understanding of the papers and findings.

Persuasive in-depth, comprehensive summaries about how the findings from the research papers are highly relevant to answer the stated research question.

Includes all  requirements of a P1 AND
providesa thorough, more advanced critical analysis of the high quality, relevant research papers and findings.

Persuasive clear, succinctsummaries about how the findings from the research papers are highly relevant to answer the stated research question.

Adequate identification of four relevant research papers.

Citation -correct use of UniSA (2015) Harvard author-date.

Statement of author’s viewpoint in student’s own words demonstrates an adequateunderstanding of each paper.

Summary of findings in student’s own wordsshows adequateunderstanding of papers

Satisfactorycomments on the usefulness (relevance) and/or limitations of research papers to answer research question

Adequateevaluative comment on the work, taking into account how findings from papers could be relevant to the question.    Limitedattempt to summarizefour research papers. Some papersnot high quality.

Citation – mostly correct

Statement of author’s viewpoint in student’s own words shows abasic understanding of each paper.

Summary of research findings in student’s own words shows a basic understanding.

Limited, basic comments on the usefulness (relevance) and/or limitations of research papers to answer question.

Limited, basic evaluative comment on how findings could be relevant to the research question.    Less than fourrelevant research papers summarized.Some not research based or not relevant to question.
Incorrect citation

Statement of author’s viewpoint  and/or findings in student’s own words demonstrates inadequate or incorrect understanding of papers

Inadequate or incorrect comments on usefulness and/or limitations of papers to answer question

Inadequate or incorrect evaluative comment on how findings are relevant to the research question     As for FIAND
incorrect summaries

Abstracts used.

All papers not research based.

Discussion

(550 words)

40 marks

Includes all requirements of a DistinctionANDdemonstrates an exceptional critical analysis and capacity for higher order, original, creative thinking.

Argumentexemplary, reflecting a strong understanding of the research papers and literature in the field.

Sophisticated ability to integrate an impressive range of additional relevant literature.    Includes all requirements of a CreditANDhigh level comprehensive analysis and synthesis explainswhythe research papers are relevant and how findings answer the research question.
Comprehensive attempt to compare and contrast findings, includes points of agreement and differing views, deficiencies in the papers.Existing gaps in knowledge or practice identified.
Discussion supported by wide range of additional relevant literature.
Includes all requirements of a P1ANDadvanced analysis and synthesis of findings to explainwhy the research papers are relevant and how the quality of the findings answers the research question

Advanced attempt to compare and contrast findings, includes points of agreement and differing views, deficiencies in the papers.Existing gaps in knowledge or practice identified.
Discussion supported by 3-5 sources of relevant additional literature.    Adequate attempt to summarize and synthesizefindingsto explainwhy the research papers are relevant and how the quality of the findings answers the research question.

Mostly satisfactory attempt to compare and contrast findings, includes points of agreement and differing views, deficiencies in the papers.

Some existing gaps in knowledge or practice identified.

Satisfactorydiscussion supported by 1-2 sources of relevant additional literature.    Limitedattempt to summarize and synthesizethe findings from research papers.

Limitedbasicdiscussion of areas of agreement in views, differing views, deficiencies in the papers.

Gaps not identified in knowledge required to improve practice.

Little evidence of gaining new understandings about the research question.
No additional relevant literature used.    Did not address all required components, inadequate
incorrect
discussion of overall findings& gap/s identified in knowledge required to improve practice.

Did not identify areas of agreement in views, differing opinions, contrasting views deficiencies in papers.
As for Fail 1 &/or incorrect discussion of all overall findings.

Failed to identify gap/s in knowledge required to improve practice.

No discussion.

Conclusion

(150 words)

10 marks    As for DistinctionANDexceptional critical interpretation, stimulates new thoughts.    As for CreditANDhigh levelcomprehensive relevant conclusion with links to theory and accurate future directions.    Includes allrequirements ofP1ANDa clear succinct conclusion, summarizes major points in a synthesized non-repetitive manner, clear future directions.     Satisfactory conclusion,clearly written and relevant to the research question.

Summarizes most main points in a non-repetitive manner.    Limited, superficial or unclear conclusion.

Limited relevance to research question.
May lack depth.    Inadequate conclusion, vague, not relevant to the research question.    No conclusion provided.
Overall writing and presentation
Adhered to all guidelines of Distinction ANDexceptionalexemplary work.    Adhered to all guidelines of P1/CreditAND
presents
high level,comprehensive work.
Adhered to all guidelines of P1ANDPresents response in a clear succinctand usually thoughtful manner.
Adheres to all guidelines re:  sentence & paragraph structure, grammar, vocabulary, spelling,
punctuation,
use of 3rd person,
use of inclusive  language,
Word limit met
sequencing of ideas, logical flow.    The response is adequately developed but some sections are not clear, thoughtful and/or not well organised.
Adheres to most guidelines re: sentence & paragraph structure, grammar, vocabulary, spelling, punctuation,
use of 3rd person,
use of inclusive language,

Word limit met,
mostly sequenced and
logical flow.    Response inadequately developed and/or lacking in clarity and thought in some areas
Paper written at a limited level with some problems with: sentence & paragraph structure, grammar, vocabulary, spelling, punctuation, use of 3rd person, inclusive language,

Adhering to word limit sequencing of ideas and logical flow    Response inadequately developed throughoutand/or lacking in clarity and thought.
Report poorly written re: sentence & paragraph structure,
grammar, vocabulary, spelling,
punctuation, use of
3rd person,
inclusive language,
Below or above word limit, poorly sequenced,
poor logical flow    As for F1 &adheres to few guidelines. Very poor. No logical flow.Well below well above word limit
Referencing & Academic Integrity
Extensive sourcesand Reference List correctly referenced as per UniSA(2015) Harvard Guidelines.     Multiple sourcesand Reference Listcorrectly referenced as per UniSA (2015) Harvard System Guidelines    All sources and Reference List correctly referenced as per UniSA (2015) Harvard System Guidelines. In-text references integrated.     Adheres to UniSA (2015) Harvard author-date system for and Reference List and in-text referencing, with no evidence of plagiarism.
In-text references mostly use author date.  The reference list is complete and mostly correct according to the UniSA.    Mostly correct use of UniSA (2015) Harvard author-date system for in-text referencing, Reference List, with no evidence of plagiarism. The reference has some inconsistencies in formatting and omissions according to the UniSA Harvard style guide     In-text referencing is incorrect or incomplete
Reference list is incorrect or incomplete. Some evidence of plagiarism.
Possible referral to AIO

No references in text. No reference list.
Extensive plagiarism
Refer to AIO

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