Effects of switching from an AChE inhibitor to a dual AChE-BuChE inhibitor in patients with Alzheimer's disease

ABSTRACT

Objective: Cholinesterase (ChE) inhibitors are the only medications approved for the treatment of Alzheimer's disease (AD). The features of ChE inhibitors differ considerably. In addition to acetylcholinesterase (AChE) inhibition, rivastigmine also inhibits butyrylcholinesterase (BuChE), providing dual AChE and BuChE inhibition. An observational study was performed to determine the response in routine clinical practice to switching AD patients to rivastigmine from a selective AChE inhibitor when that treatment no longer delivered a satisfactory clinical response.

Research design and methods: A prospective, multicentre, 3‐month observational trial in patients with mild to moderately severe AD (adjusted Mini Mental State Examination [MMSE] score 10–26) deteriorating (at least 2 adjusted MMSE points in last 6 months) on selective AChE inhibitor treatment. Adjusted MMSE, activities of daily living (ADL) and instrumental activities of daily living (IADL), the Zarit caregiver burden and global function (short Clinical Global Impression of Change, CGIC) scores were noted before the switch and 3 months after the switch.

Results: 225 patients entered the study. The switches made were from donepezil to rivastigmine (D‐R) in 188 patients, galantamine to rivastigmine (G‐R) in 33 patients and donepezil to galantamine (D‐G) in four patients. Ten patients discontinued due to adverse events and eight for other reasons. More than half of the switches were within 36 hours of a patient's first treatment visit. In the D‐R and G‐R groups, 67.7% and 66.7% of patients responded (CGIC score ≤ 4), respectively. In non-responders, worsening (CGIC score 5–7) was mild in approximately 80% or more of patients. Adjusted MMSE improved after the switch from both donepezil and galantamine to rivastigmine (+0.69 ± 3.2, p = 0.008 and +0.6 ± 1.6, p = 0.05, respectively). Mean ADL, IADL and Zarit scores remained stable. The proportion of patients on concomitant antipsychotic therapy diminished by 30.5% and benzodiazepines were discontinued in all patients, except one.

Conclusions: AD patients deteriorating on selective AChE inhibitor treatment can benefit from switching to a dual AChE-BuChE inhibitor, such as rivastigmine, in terms of stabilization of disease, improvement in cognitive function and reduction in the burden of concomitant psychoactive treatment. The switch was well tolerated. Confirmation of these results is required in a controlled study.     

Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer's disease over a 2-year period

ABSTRACT

Objectives: Randomised controlled trials that directly compare cholinesterase inhibitors for the treatment of Alzheimer's disease have been characterised by significant methodological limitations. As a consequence, they have failed to establish whether there are differences between agents in this class. To help address this question, a double-blind, randomised, controlled, multicentre trial was designed to evaluate the efficacy and tolerability of cholinesterase inhibitor treatment in patients with moderate to moderately-severe Alzheimer's disease over a 2-year period.

Methods: Patients were randomly assigned to rivastigmine 3–12?mg/day or donepezil 5–10?mg/day. Efficacy measures comprised assessments of cognition, activities of daily living, global functioning and behavioural symptoms. Safety and tolerability assessments included adverse events and measurement of vital signs.

Results: In total, 994 patients received cholinesterase inhibitor treatment (rivastigmine, n = 495; donepezil, n = 499), and 57.9% of patients completed the study. The most frequent reason for premature discontinuation in both treatment groups was adverse events, primarily gastrointestinal. Adverse events were more frequent in the rivastigmine group during the titration phase, but similar in the maintenance phase. Serious adverse events were reported by 31.7% of rivastigmine- and 32.5% of donepezil-treated patients, respectively. Rivastigmine and donepezil had similar effects on measures of cognition and behaviour, but rivastigmine showed a statistically significant advantage on measures of activities of daily living and global functioning in the ITT–LOCF population. However, this was not maintained in the non-ITT–LOCF populations. In secondary sub-group analyses, AD patients who had genotypes that encoded for full expression of the butyrylcholinesterase enzyme (BuChE wt/wt; n = 226/340), who were < 75 years of age (n = 362/994) or who had symptoms suggestive of concomitant Lewy body disease (n = 49/994) showed significantly greater benefits from rivastigmine treatment.

Conclusions: Cholinesterase inhibitor treatment may offer continued therapeutic benefit for up to 2 years in patients with moderate AD. Although both drugs performed similarly on cognition and behaviour, rivastigmine may provide greater benefit in activities of daily living and global functioning.     

多奈哌齐单用及与美金刚联用治疗中、重度阿尔茨海默病的临床对比研究

目的:探讨多奈哌齐单用及与美金刚联用治疗中、重度阿尔茨海默病(AD)的临床疗效和安全性。方法:选取2018年3月至2020年3月于四川省医学科学院·四川省人民医院(东院)就诊的100例中、重度AD患者作为研究对象,采用随机数字表法将其分为对照组和治疗组,各50例。对照组给予多奈哌齐单药治疗(初始剂量为5 mg/d,睡前服用;4周后剂量改为10 mg/d,睡前服用,服药时间共为6个月)。治疗组患者在对照组治疗基础上联用美金刚治疗(初始剂量为5 mg/d,如无不良反应者每周剂量增加5 mg,直至增加至20 mg/d,服药时间共为6个月)。比较两组患者治疗前后蒙特利尔认知评估量表(MoCA)评分、简易智力状态检查量表(MMSE)评分、日常生活能力量表(ADL)评分及治疗有效率和不良反应发生情况。结果:与同组治疗前比较,两组患者治疗后的MoCA、MMSE和ADL评分均显著升高(P<0.05)。治疗后,与对照组比较,治疗组患者MoCA、MMSE、ADL评分和总有效率均显著升高(P<0.05),而不良反应发生率显著降低(P<0.05)。结论:多奈哌齐联合美金刚相较于多奈哌齐单药治疗中、重度AD具有更好的临床疗效,更有助于改善AD患者的神经功能,且安全性较好。     

Functional,Cognitive and Behavioral Effects of Donepezil in Patients with Moderate Alzheimer's Disease

Summary

Objective: To investigate the efficacy and safety of donepezil in a subgroup of patients with Alzheimer's disease (AD) of moderate severity from a previous trial.

Methods: Two hundred and seven patients with moderate AD (standardized Mini-Mental State Examination [sMMSE] score 10-17) were randomized to treatment in this 24-week, double-blind, placebo-controlled trial. Patients received either donepezil, 5mg/day for the first 28 days and 10mg/day thereafter according to the clinician's judgement (n?=?102), or placebo (n?=?105). The primary outcome measure was the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC-plus) at week 24 using a last observation carried forward (LOCF) analysis.

Results: Baseline patient demographics were similar between treatment groups. Mean age was 74.3 years (range 48–92). Least-squares (LS) mean sMMSE scores at baseline were 13.6?±?0.3 for the donepezil group and 13.9?±?0.3 for the placebo group. LS mean

CIBIC-plus scores for donepezil-treated patients were improved from, or close to, baseline severity at all visits, and were significantly different from placebo at weeks 8,12,18, and 24 (week 24 LOCF mean difference?=?0.53, p?=?0.0003). LS mean change from baseline scores on the sMMSE and Severe Impairment Battery (SIB) for the donepezil group improved throughout the study, and were significantly different from placebo at each visit for the sMMSE (week 24 LOCF mean difference?=?2.06, p?=?0.0002) and from week 8 for the SIB (week 24 LOCF mean difference?=??4.44, p?=?0.0026). LS mean change scores on the Disability Assessment for Dementia remained at or above baseline levels throughout the study for the donepezil group, while the placebo group showed a steady decline; treatment differences were significant at each visit (week 24 LOCF mean difference?=??9.25, p?<?0.0001). LS mean change scores on the Neuropsychiatric Inventory 12-item total improved throughout the study for the donepezil group and were significantly

different from placebo at weeks 4 and 24 (week 24 LOCF mean difference?=?5.92, p?=?0.0022). Eighty-one per cent of donepezil-treated and 89% of placebo-treated patients completed the trial, with 9% and 5%, respectively, discontinuing due to adverse events (AEs). Eighty-two per cent of donepezil-treated and 80% of placebo-treated patients experienced AEs, the majority of which were rated mild in severity and, in general, were similar between treatment groups.

Conclusion:The significant treatment responses observed with donepezil in these patients reinforce the findings from earlier studies that show donepezil to have important benefits, compared with placebo, across functional, cognitive, and behavioral symptoms, with good tolerability, in patients with AD of moderate severity.     

Effect of age on response to rivastigmine or donepezil in patients with Alzheimer's disease

ABSTRACT

Background: Younger Alzheimer's disease (AD) patients appear to differ genetically and neuropathologically from older AD patients, and may experience a more aggressive disease course compared with older patients. A randomised trial investigated the efficacy and tolerability of rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and donepezil, an AChE-selective inhibitor, in patients with AD over a 2-year period. This retrospective analysis investigated whether younger and older patients showed differential tolerability and efficacy responses to cholinesterase inhibitor treatment.

Methods: For the current analysis, patients were divided according to age at baseline: those aged < 75 years and those aged ≥ 75 years. Efficacy measures were the Severe Impairment Battery (SIB), Neuropsychiatric Inventory (NPI), Global Deterioration Scale (GDS), Mini-Mental State Examination (MMSE) and the AD Cooperative Study Activities of Daily Living scale (ADCS‐ADL). Changes in efficacy parameters and adverse event frequencies were calculated for rivastigmine and donepezil-treated patients in both age groups. Exploratory analyses were also conducted on SIB, ADCS‐ADL and NPI in patients who consented to pharmacogenetic testing at baseline. Genotyping of the apolipoprotein E (APOE) ε4 allele and the BuChE K-variant was conducted using the TaqMan assay. Main efficacy analyses were based on an intent-to-treat last observation carried forward (ITT‐LOCF) population.

Results: Of the 994 patients who received the study drug, 362 (36.4%) were younger than 75 years and 632 (63.6%) were aged 75 years or over. Rivastigmine provided significant benefits in younger patients compared with donepezil on the NPI‐10, NPI‐12, NPI‐D, GDS and ADCS‐ADL (all p < 0.05, ITT‐LOCF). With the exception of the NPI‐D in favour of donepezil (?p < 0.05, ITT‐LOCF), no significant treatment differences were observed in older patients. Younger patients with two wild-type BuChE alleles had a significantly greater response to rivastigmine than donepezil on the ADCS‐ADL (?p < 0.01, ITT‐LOCF) and SIB (?p < 0.05, ITT‐LOCF). The most common adverse events were nausea and vomiting and these were more frequent in rivastigmine-treated patients.

Conclusion: In this sub group analysis, patients younger than 75 years of age showed greater treatment responses to rivastigmine than donepezil. Analysis of response by BuChE genotype suggests that this differential effect may be due to the inhibition of BuChE, in addition to AChE, by rivastigmine.     

Understanding and Managing Behavioural Symptoms in Alzheimer's Disease and Related Dementias: Focus on Rivastigmine

Summary

Behavioural and psychological symptoms of dementia (BPSD) are among the most distressing manifestations of dementia and result in considerable social and economic costs. Practical, non-pharmacological approaches such as environmental and behavioural changes may provide some benefit for patients in managing mild BPSD. In addition, various pharmacological approaches to treatment have been employed, such as neuroleptics and atypical antipsychotics, which differ in neurochemical target and clinical effectiveness. Growing evidence suggests that the neurobiological basis of BPSD in Alzheimer's disease (AD) and related dementias is a loss of cholinergic neurones and a resultant decline in acetylcholine (ACh) in brain regions which regulate behavioural and emotional responses, such as the limbic system. This cholinergic deficit can be partly corrected by inhibiting cholinesterase enzymes (ChEs). Studies of ChE inhibitors have shown positive effects to improve or stabilise existing BPSD and delay the emergence of new behavioural symptoms. In placebo-controlled studies, donepezil has reported efficacy in non-institutionalised moderate to moderately severe patients over a period of 24 weeks, but has failed to demonstrate efficacy in mild to moderate AD and in institutionalised patients with severe disease. Galantamine has been shown to delay the onset of BPSD in mild to moderate AD patients in one placebo-controlled study, and improve BPSD in a similar study of patients with cerebrovascular disease or probable vascular dementia. Studies with rivastigmine have shown efficacy in placebo-controlled studies of mild to moderately severe AD and in patients with Lewy body variant AD. Institutionalised patients with severe disease also show symptomatic benefits in BPSD with rivastigmine, resulting in a reduction in concomitant psychoactive medication use. Symptom complexes responding to ChE inhibitors appear to differ - all agents improve apathy, depression and anxiety, while rivastigmine additionally improves hallucinations and delusions, possibility as a result of dual inhibition of acetylcholinesterase and butyrylcholinesterase. The presence of hallucinations has been shown to predict response to rivastigmine. Accumulating data from studies of ChE inhibitors suggest that early intervention and long-term treatment, in addition to providing cognitive benefits, improves BPSD and offers potential to enhance quality of life. Differences seen between the agents in terms of efficacy in BPSD, tolerability and safety profiles may be the result of differences in neuropharmacological profiles.     

Rivastigmine: an update on therapeutic efficacy in Alzheimer's disease and other conditions

SUMMARY

The results of recent clinical trials with rivastigmine show that in the approved indication of mild to moderate Alzheimer's disease (AD), the drug is effective in the long term. Rivastigmine produces a significant delay in the decline of the three components of AD that have been identified by European guidelines as essential parameters for the assessment of therapeutic efficacy of medicinal products with this indication. These are cognitive function, the ability to perform the usual activities of daily living, and global judgement of the patient's condition by the patient himself, his caregiver and his doctor. Moreover, rivastigmine produces significant control of AD behavioural disorders. This further reduces caregiver burden, reduces the probability of institutionalisation, and enables the reduction or discontinuation of expensive and poorly tolerated antipsychotics. Recent trials also suggest that rivastigmine is effective in moderate to severe Alzheimer's disease, 'mixed' dementia (AD associated with vascular disorders) and Lewy body dementia. Preliminary investigations have also indicated that the drug may provide important benefits in patients with vascular dementia or dementia associated with Parkinson's disease. Pharmacoeconomic studies show that the therapeutic properties of rivastigmine result in economic savings for the care of demented patients living in the community.     

卡巴拉汀治疗阿尔茨海默病的脑局部一致性研究

目的 通过局部一致性（regional homogeneity,ReHo）分析方法探究卡巴拉汀治疗阿尔茨海默病（Alzheimer''s disease,AD）的脑功能影像机制。方法 9例轻中度AD患者给予卡巴拉汀治疗24周,治疗前后分别进行全面的神经心理测评和静息态功能磁共振扫描。并选取年龄、性别、受教育年限与之相匹配的健康对照组9例进行静息态功能磁共振扫描,比较卡巴拉汀治疗前后AD患者大脑ReHo值的变化。结果 与治疗前比,AD患者治疗后,表现出简易智力状态检查量表评分增加（P<0.05）,老年痴呆症评估量表-认知部分和日常生活活动能力评分降低（P<0.05）;AD患者在左内侧额上回,左侧眶内额上回和右侧杏仁核表现出ReHo值减少（P<0.05）;此外,老年痴呆症评估量表-认知部分得分变化与左侧眶内额上回ReHo值呈正相关。结论 卡巴拉汀能够改善AD的认知功能,可能是通过与认知相关的内侧额上回和杏仁核的自发脑活动来实现的,相关脑区未来有望作为此类药物疗效监测的生物学标志物。     

Donepezil in Alzheimer's disease: a clinical observational study evaluating individual treatment response

ABSTRACT

Objective: A post-marketing surveillance study evaluating the sensitivity of the Individual Symptom Score (IndiSS) in assessing the treatment benefits of donepezil in patients with Alzheimer's disease (AD) under everyday conditions.

Research design and methods: For each patient, up to three ‘especially relevant’ individual symptoms were defined and evaluated during donepezil treatment. Changes were scored on a five-point Likert-type scale, ranging from ‘markedly improved’ (+2) to ‘markedly worsened’ (–2). The mean score for all IndiSS items was calculated after 3 and 6 months. Positive values represented treatment success. In addition, patients with concomitant parkinsonian symptoms (PS+) or cerebrovascular disease (CVD+) were compared with those with neither condition.

Results: A total of 2046 patients with AD enrolled. The most frequent IndiSS items were (% patients): memory (24%), disorientation (14%) and loss of initiative/apathy (9%). The mean IndiSS for the overall patient population was +0.7 ± 0.7 points after 3 months and +0.9 ± 0.8 after 6 months. Patients with concomitant PS+ or CVD+ showed similar improvements in IndiSS.

Conclusion: Identification and follow-up of individual symptoms is a useful tool for evaluating therapy response to donepezil in everyday practice. Patients with concomitant PS+ or CVD+ benefit from donepezil therapy and show a similar side-effect profile.     

Donepezil treatment in severe Alzheimer's disease: a pooled analysis of three clinical trials

Abstract

Objective:

Individual clinical trials have demonstrated benefits of donepezil in patients with severe Alzheimer's disease (AD). Data were pooled from three randomized, placebo-controlled trials of donepezil for severe AD to further evaluate treatment effects and overall tolerability/safety.     

Rivastigmine for the Treatment of Dementia and Visual Hallucinations Associated with Parkinson's Disease: A Case Series

Summary

Parkinson's disease patients may suffer from cognitive impairment and behavioural problems such as apathy, personality changes, speech disturbances and visual hallucinations (Parkinson's disease dementia). However, there is currently no recommended treatment for Parkinson's disease dementia and antipsychotic agents can worsen extrapyramidal symptoms, making them unsuitable for patients with this condition. The observation that patients with Parkinson's disease dementia have extensive cholinergic deficits led to the hypothesis that cholinesterase inhibitors may provide benefits for patients with this condition. Here, we present a case series of patients with Parkinson's disease and dementia who we treated with rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) that shows brain region-selectivity. The introduction of rivastigmine led to improvements in cognitive and functional abilities, as well as the resolution of behavioural problems and visual hallucinations. Rivastigmine was well tolerated by our patients when the dose was escalated slowly, including one patient who had previously experienced severe side-effects with the AChE-selective inhibitor donepezil. Despite the large number and range of concomitant medications being received by the patients, no side-effects thought to be related to drug-drug interactions were reported. A large, placebo-controlled study is warranted to ascertain the full clinical profile of rivastigmine in Parkinson's disease dementia.     

复方海蛇胶囊联合多奈哌齐治疗阿尔茨海默病的Meta分析

目的 系统评价复方海蛇胶囊联合多奈哌齐治疗阿尔茨海默病的疗效与安全性。方法 计算机检索PubMed、维普中文数据库（VIP）、中国知网（CNKI）、万方医学网及中国生物医学文献数据库（CBM）,收集复方海蛇胶囊联合多奈哌齐（试验组）对比单用多奈哌齐（对照组）治疗阿尔茨海默病的随机对照研究（RCT）,检索时限2000年1月—2017年2月。筛选文献、提取数据并对纳入RCT进行方法学质量评价,采用RevMan 5.0软件对各效应指标进行Meta分析。结果 共纳入8篇RCT,合计605例患者。Meta分析结果显示：试验组在简易智能精神状态量表评分[P<0.001,MD=2.69,95% CI=（1.46,3.92）]、认知初级量表评分[P<0.001,MD=-4.54,95% CI（-5.64,-3.43）]和日常生活能力量表评分[P<0.001,MD=-3.60,95% CI（-4.53,-2.66）]方面与对照组比较,差异有统计学意义;试验组与对照组不良反应发生率相当[P=0.94,OR=1.02,95% CI（0.63,1.66）],差异无统计学意义。结论 复方海蛇胶囊联合多奈哌齐治疗阿尔茨海默病的临床疗效优于单用多奈哌齐,且联用未导致不良反应增加。     

Effectiveness of open-label donepezil treatment in patients with Alzheimer's disease discontinuing memantine monotherapy*

ABSTRACT

Objective: To evaluate the efficacy and safety of donepezil in patients with Alzheimer's disease (AD) who discontinue memantine due to a lack of efficacy or not being well tolerated.

Methods: This study enrolled patients with moderate-to-severe AD (Mini-Mental State Examination [MMSE] score 5–17) who had a history of treatment with memantine monotherapy (10?mg/BID) for ≥?3 months prior to screening and maintained until study baseline. For inclusion in this study, the patient's memantine treatment had to have been judged as lacking efficacy or not well tolerated at the screening visit. Information on previous memantine use was also obtained with regard to dose and duration of treatment. At the baseline visit, patients were switched to open-label donepezil 5?mg/day for 4 weeks, and 10?mg/day thereafter. The primary efficacy measure was a change in MMSE at week 12 using a last observation carried forward (LOCF) analysis. Secondary measures included Physician and Caregiver Satisfaction Questionnaires (PSQ, CSQ), the Clinical Global Impression-Improvement (CGI‐I), Neuropsychiatric Inventory (NPI), and a Caregiver Diary (CD).

Results: At week 12‐LOCF, MMSE scores increased by a mean of 1.55 points from baseline (?p < 0.0001). At end point, the PSQ and CSQ indicated consistent improvements in satisfaction/ease of use with donepezil; 60.2% of patients improved on the CGI‐I; and 44.4–55.6% improved on each of three components of the CD. Improvements on the MMSE, CSQ, and CGI‐I were apparent, irrespective of previous cholinesterase (ChE) inhibitor use. No significant effects were seen for the total score on the NPI. Withdrawal rates (8.7% due to adverse events [AEs]) and AEs were consistent with the known donepezil safety profile.

Conclusion: Donepezil was effective and well tolerated in moderate-to-severe AD patients who discontinued memantine monotherapy, including those with previous exposure to ChE inhibitors.     

盐酸美金刚与多奈哌齐治疗阿尔茨海默病的对照研究

目的探讨盐酸美金刚与多奈哌齐治疗阿尔茨海默病（AD）的临床疗效及安全性。方法将96例AD患者随机分为盐酸美金刚组和多奈哌齐组,在治疗前、治疗后2周、4周、8周、16周、24周末分别进行简易智能状态检查（MMSE）评分和临床疗效评估。结果在治疗2、4、8周末评估两组相仿,第16、24用末多奈哌齐组优于盐酸美金刚组。结论盐酸美金刚与多奈哌齐短期疗效相仿,多奈哌齐组远期疗效优干盐酸美金刚组,两组均有良好的安全性。     

二活附子方治疗强直性脊柱炎的临床疗效及安全性评价

目的：评价中药二活附子方治疗强直性脊柱炎( ankylosing spondylitis, AS)的临床疗效及安全性。方法采用前瞻性随机对照临床试验,将78例AS患者随机分入观察组和对照组,观察组给予二活附子方,对照组给予柳氮磺胺吡啶片口服,疗程12周,疗效评价采用ASAS20、ASAS40及BASDAI50标准及中医证候疗效评价标准。观察治疗前后患者Bath强直性脊柱炎疾病活动指数( BASDAI)、Bath强直性脊柱炎功能指数( BASFI)、Bath强直性脊柱炎测量指数( BASMI)、脊柱痛评分、夜间痛评分、患者总体评价( PGA)、红细胞沉降率( ESR)及C反应蛋白( CRP)等指标。结果治疗4周后,观察组达到ASAS20标准的患者例数多于对照组(P<0．05)。治疗12周后,观察组达到ASAS20、ASAS40、BASDAI50标准的患者例数多于对照组(P<0．05);中医证候疗效观察组高于对照组(P<0．05);两组治疗后中医证候积分、BASDAI、BASFI、脊柱痛评分、夜间痛评分、PGA均优于治疗前(P<0．05,P<0．01),且观察组上述指标改善情况均优于对照组(P<0．05);两组治疗后ESR、CRP较治疗前降低(P<0．05);两组不良反应发生率比较,差异无统计学意义(P>0．05)。结论应用二活附子方治疗AS疗效确切且安全性较高。     

A review of compliance to treatment in Alzheimer's disease: potential benefits of a transdermal patch

ABSTRACT

Background: Following prescribed medication regimens is essential for the effective treatment of any medical condition. Unfortunately, patients often fail to follow recommendations, and treatment non-compliance represents a widespread, often underestimated problem, placing tremendous burden on the healthcare system. Compliance in Alzheimer's disease (AD), a chronic neurodegenerative disease typically afflicting older adults, is especially challenging.

Scope: To review factors contributing to poor treatment compliance in AD, considering the prominent role care­givers often play in treatment management; and acknowledging strategic approaches, particularly modern transdermal patches, to improve compliance in this particularly susceptible population. Articles were identified by searching MEDLINE in November 2006 (search limits: 1987–2007) using the terms: compliance; Alzheimer's; treatment; and transdermal. Additional resources included bibliographies of identified articles.

Findings: Strategic approaches to improving treatment compliance include: simplifying treatment regimens, using reminder packaging, and developing more patient- or caregiver-friendly modes of administration. To date, AD therapies have been administered orally. However, recent developments in alternative modes of drug delivery, such as transdermal patches, may offer effective, well-tolerated treatment options with the potential to enhance compliance. A patch containing rivastigmine (Exelon*), an established cholinesterase inhibitor, has been developed and demonstrated to have good efficacy and tolerability in patients with AD. In addition, initial caregiver experience suggests preference for the patch over oral administration.

Conclusion: Transdermal patches may be an effective way to optimize treatment compliance for AD, as well as an increasing number of other chronic conditions that typically afflict the older population, offering the possibility of more sustained clinical benefits.     

The cognitive effects of cholinesterase inhibitor treatment in every-day practice

ABSTRACT

Objective: Cholinesterase inhibitors (ChEIs) are the treatment of choice in Alzheimer's disease (AD). Their efficacy has been proven in many clinical trials. The aim of the present study was to confirm their cognitive benefit in every day practice as to whether it is similar to that expected from clinical trials.

Patients and methods: We reviewed the files of 41 patients suffering from AD or mixed dementia and treated by ChEIs in terms of every day practice.

Results: During the first year MMSE scores remained better than or at baseline levels. Following that a gradual decline was noted. However, at any time point, the observed scores were significantly better than the expected ones calculated according to the pre-treatment rate of decline. The post-treatment rate of decline was significantly better than the pre-treatment one, while progression to the next stage of dementia was delayed by 8 months.

Conclusion: The present observations from every-day practice indicate that there is a small but significant effect of ChEIs in cognition, similar to that observed in clinical trials. Furthermore, a small but significant delay in dementia progression may occur after treatment with ChEIs.     

Impact of donepezil treatment for Alzheimer's disease on caregiver time

SUMMARY

Objective: To assess the impact of donepezil treatment compared with placebo on caregiver time spent assisting patients with Alzheimer's disease (AD).

Research design and methods: Patient and caregiver data were collected as part of a 1-year, prospective, double-blind, randomized, placebo-controlled trial. The Resource Utilization in Dementia (RUD) questionnaire was used to record caregiver time at study baseline and at Weeks 12, 24, 36, and 52. This analysis focuses solely on those caregivers who were actively (> 0?h/day reported on the RUD) providing care at study baseline.

Main outcome measures: The change in time relative to baseline that caregivers spent assisting patients over the course of the study.

Results: The active caregiver population was composed of 96 caregivers of donepezil-treated patients and 94 caregivers of patients receiving placebo. Over the course of the 1-year study, and as the condition of the AD patients deteriorated, it was expected that caregiver time would increase. As expected, after 52?weeks, caregivers of placebo patients were providing almost 2?h each day (106.8?min) more care than they had done at study baseline. For those caregivers of donepezil-treated patients, although they were spending more time caring than they had done at study baseline, their time burden had only increased by 42.6?min more each day. This difference in caring time between the 2 groups, relative to baseline at Week 52, was 1.1?h (64.2?min) each day, and was significant (?p = 0.03).

Conclusion: Caregiver time devoted to helping an AD patient typically increases with the severity of the disease. By helping the patient maintain his/her ability to perform activities of daily living for longer, treatment with donepezil is not only beneficial to the patient, but also has positive time-burden implications for the caregiver.