Sleep disturbance in mild to moderate Alzheimer's disease

BACKGROUND AND PURPOSE: To determine the prevalence of sleep disturbance in a memory clinic population of Alzheimer's disease (AD) patients and identify its clinical correlates. PATIENTS AND METHODS: Data from 215 attendees at a memory clinic, who were diagnosed with Alzheimer's disease, were examined. This included data from cognitive, functional and neuropsychological assessments. Sleep disturbance was determined using the question about diurnal rhythm disturbance on the BEHAVE-AD questionnaire. Two groups, with and without sleep disturbance, were compared. Group differences were analysed using univariate analysis and stepwise logistic regression analysis. RESULTS: The prevalence of sleep disturbance in this sample was 24.5%. The BEHAVE-AD 'aggressiveness' (P=0.009) and 'global rating' (P=0.029) (a measure of global impact of behavioural disturbance) were found to be significant predictors of sleep disturbance in AD. CONCLUSIONS: Sleep disturbance in AD is associated with other behavioural symptoms, notably aggressiveness. Sleep disturbance in AD has significant impact on the patient and/or caregiver. Consideration of co-morbid behavioural symptoms may aid the clinician in choosing a suitable treatment for sleep disturbance in AD.     

Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind,randomised, placebo controlled trial

OBJECTIVE: To assess the efficacy and safety of Melissa officinalis extract using a fixed dose (60 drops/day) in patients with mild to moderate Alzheimer's disease. DESIGN: A four month, parallel group, placebo controlled trial undertaken in three centres in Tehran, Iran. METHODS: Patients with mild to moderate Alzheimer's disease aged between 65 and 80 years (n = 42; 18 women, 24 men) with a score of >or= 12 on the cognitive subscale of Alzheimer's disease assessment scale (ADAS-cog) and 相似文献   

Efficacy of a medical food in mild Alzheimer's disease: A randomized,controlled trial

ObjectiveTo investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD).MethodsA total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a control drink, taken once-daily for 12 weeks. Primary outcome measures were the delayed verbal recall task of the Wechsler Memory Scale–revised, and the 13-item modified Alzheimer's Disease Assessment Scale–cognitive subscale at week 12.ResultsAt 12 weeks, significant improvement in the delayed verbal recall task was noted in the active group compared with control (P = .021). Modified Alzheimer's Disease Assessment Scale–cognitive subscale and other outcome scores (e.g., Clinician Interview Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric Inventory, Alzheimer's disease Co-operative Study–Activities of Daily Living, Quality of Life in Alzheimer's Disease) were unchanged. The control group neither deteriorated nor improved. Compliance was excellent (95%) and the product was well tolerated.ConclusionsSupplementation with a medical food including phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal recall) in mild AD patients. This proof-of-concept study justifies further clinical trials.     

Efficacy of Souvenaid in mild Alzheimer's disease: results from a randomized, controlled trial

Souvenaid aims to improve synapse formation and function. An earlier study in patients with Alzheimer's disease (AD) showed that Souvenaid increased memory performance after 12 weeks in drug-na?ve patients with mild AD. The Souvenir II study was a 24-week, randomized, controlled, double-blind, parallel-group, multi-country trial to confirm and extend previous findings in drug-na?ve patients with mild AD. Patients were randomized 1:1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. The primary outcome was the memory function domain Z-score of the Neuropsychological Test Battery (NTB) over 24 weeks. Electroencephalography (EEG) measures served as secondary outcomes as marker for synaptic connectivity. Assessments were done at baseline, 12, and 24 weeks. The NTB memory domain Z-score was significantly increased in the active versus the control group over the 24-week intervention period (p = 0.023; Cohen's d = 0.21; 95% confidence interval [-0.06]-[0.49]). A trend for an effect was observed on the NTB total composite z-score (p = 0.053). EEG measures of functional connectivity in the delta band were significantly different between study groups during 24 weeks in favor of the active group. Compliance was very high (96.6% [control] and 97.1% [active]). No difference between study groups in the occurrence of (serious) adverse events. This study demonstrates that Souvenaid is well tolerated and improves memory performance in drug-na?ve patients with mild AD. EEG outcomes suggest that Souvenaid has an effect on brain functional connectivity, supporting the underlying hypothesis of changed synaptic activity.     

Memantine in moderate to severe Alzheimer's disease: a meta-analysis of randomised clinical trials

The efficacy of memantine in Alzheimer's disease (AD) has been investigated in multiple randomised, placebo-controlled phase III trials. Recently, the indication label for memantine in Europe was extended to cover patients with moderate to severe AD, i.e. Mini-Mental State Exam total scores below 20. The efficacy data for memantine in this patient subgroup has been summarised by a meta-analysis of 1,826 patients in six trials. Efficacy was assessed using measures of global status (Clinician's Interview-Based Impression of Change Plus Caregiver Input), cognition (Alzheimer's Disease Assessment Scale - Cognitive Subscale, or Severe Impairment Battery), function (Alzheimer's Disease Cooperative Study Activities of Daily Living 19- or 23-item scale), and behaviour (Neuropsychiatric Inventory). Results (without replacement of missing values) showed statistically significant effects for memantine (vs. placebo) in each domain. Memantine was well tolerated, and the overall incidence rates of adverse events were comparable to placebo. This meta-analysis supports memantine's clinically relevant efficacy in patients with moderate to severe AD.     

Improving drug trials for mild to moderate Alzheimer's disease

Over the last two decades, numerous studies have been conducted on subjects with mild to moderate Alzheimer's disease. The objective of this paper was to review concerns raised in the literature about the design and methodology of these clinical trials and to make recommendations to deal with the limitations identified. Concerns raised in the literature include the following: undue focus on statistical rather than clinical significance; the need for further pharmacoeconomic evaluations; the nonrepresentativeness of the study populations; perceived inadequacies in the direct-comparison studies conducted to date; the limitations of open-label extension studies; the inability of standard psychometric tools to document all the relevant treatment effects; the ethics of placebo-controlled trials; and, problems caused by the actions of the regulatory authorities. Recommendations are made to deal with the issues raised.     

Apraxic disturbances in patients with mild to moderate Alzheimer's disease

Twenty-two patients meeting the NINCDS–ADRDA diagnostic criteria for probable AD were included in the study, along with 10 matched controls. Praxic disturbances were investigated using eight tasks and the results were interpreted according to the neuropsychological model of Roy and Square modified by Rothi et al. (1988) [Aphasiology 21:381–388] which distinguishes a conceptual system concerned with knowledge of the action and function of gestures and a production system that effects gestures in the environment. Disturbance of the production system was found only in 17 patients. Disturbance of the production system was correlated to disturbance of verbal comprehension. The patients scored lower using the left hand than the right. Disturbance of the conceptual system was found in all patients and was not significantly correlated with other cognitive deficits. No significant difference in results was found according to the type of input to the conceptual system (visual or verbal). Deficits in tasks using real objects were correlated to disturbances of both the production and conceptual systems. Most patients performed poorly both in tasks exploring the conceptual system and in those exploring the production system. However, two patients performed badly in production tasks but had performances in the range of controls for conceptual tasks and one patient had the opposite pattern of dissociation. This provides evidence that the production and the conceptual system are independent. Impairment in the ability to perform everyday activities was correlated to disturbances of the conceptual system whereas poor performances in tasks exploring the production system or in using real objects were not.     

Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study

Memantine is a moderate affinity, uncompetitive NMDA receptor antagonist currently approved for the treatment of moderate to severe Alzheimer's disease (AD). A 24-week, double-blind, placebo-controlled, study (Study 99679) conducted in Europe evaluated the efficacy and tolerability of 20mg/day memantine in patients with mild to moderate AD. Patients were randomised to either memantine or placebo in a 2:1 ratio. Efficacy was primarily assessed as change from baseline in ADAS-cog and CIBIC-plus score. Of 470 patients randomised and treated (memantine, n=318; placebo, n=152), 85% and 91% completed the study. Memantine-treated patients showed statistically significant improvement relative to placebo at weeks 12 and 18, and numerical superiority at week 24 on both efficacy scales. The lack of significance at week 24 was attributed to an unexpectedly high placebo response. Memantine was well tolerated with an adverse event profile similar to placebo. The data presented support the efficacy of memantine in mild to moderate AD.     

Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study

Memantine is a moderate affinity, uncompetitive NMDA receptor antagonist currently approved for the treatment of moderate to severe Alzheimer's disease (AD). A 24-week, double-blind, placebo-controlled, study (Study 99679) conducted in Europe evaluated the efficacy and tolerability of 20 mg/day memantine in patients with mild to moderate AD. Patients were randomised to either memantine or placebo in a 2:1 ratio. Efficacy was primarily assessed as change from baseline in ADAS-cog and CIBIC-plus score. Of 470 patients randomised and treated (memantine, n=318; placebo, n=152), 85% and 91% completed the study. Memantine-treated patients showed statistically significant improvement relative to placebo at weeks 12 and 18, and numerical superiority at week 24 on both efficacy scales. The lack of significance at week 24 was attributed to an unexpectedly high placebo response. Memantine was well tolerated with an adverse event profile similar to placebo. The data presented support the efficacy of memantine in mild to moderate AD.     

天智颗粒治疗轻、中度阿尔茨海默病临床研究

目的评价天智颗粒治疗轻、中度阿尔茨海默病(alzheimer disease,AD)的有效性及安全性。方法选择简易智能状态量表(MMSE)轻、中度AD患者60例,随机分成治疗组和对照组各30例,治疗组给予天智颗粒联合吡拉西坦治疗,对照组给予吡拉西坦治疗,观察12周。治疗前后应用简易智能状态量表MMSE,日常生活能力量表(ADL)评价临床疗效;用不良反应量表(TESS)评定不良反应。结果观察12周,天智颗粒治疗组较对照组MMES、ADL评分明显改善(P<0.01)。治疗组天智颗粒治疗12周后较治疗前MMSE与ADL分数分别改善3.8分和8.0分(P<0.05,P<0.01)。天智颗粒治疗组不良反应轻,与吡拉西坦对照组比较2组差异无显著意义(P>0.05)。结论天智颗粒能有效治疗轻、中度AD患者,对患者的认知功能和日常生活自理能力均有改善,耐受性好,安全性高。     

Treatment of moderate to severe Alzheimer's disease: rationale and trial design

Moderate to severe Alzheimer's disease (AD) is characterized by increasing cognitive, functional, and behavioural dysfunction that results in increased caregiver burden and, eventually, complete dependence. Despite its significance as a societal health problem, there are few treatment trials of cognitive enhancers or disease modifying agents for this stage of illness. Studies suggest the cholinesterase inhibitors, especially donepezil, may provide benefit. Several studies provide support for the use of the NMDA receptor antagonist memantine as monotherapy or added to a cholinesterase inhibitor for moderate to severe AD. While there are no published guidelines for the treatment of moderate to severe AD, these studies do provide guidance for recommendations for study design and outcome measures. Such studies are urgently needed.     

An economic evaluation of donepezil in mild to moderate Alzheimer's disease: results of a 1-year,double-blind,randomized trial

The costs and consequences of donepezil versus placebo treatment in patients with mild to moderate Alzheimer's disease (AD) were evaluated as part of a 1-year prospective, double-blind, randomized, multinational clinical trial. Patients received either donepezil (n = 142; 5 mg/day for 28 days followed by 10 mg/day according to the clinician's judgement) or placebo (n = 144). Unit costs were assessed in 1999 Swedish kronas (SEK) and converted to US dollars (USD). Donepezil-treated patients gained functional benefits relative to placebo on the Progressive Deterioration Scale (p = 0.042) and Instrumental Activities of Daily Living scale (p = 0.025) at week 52. Caregivers of donepezil-treated patients spent an average of 400 h less annually providing care than caregivers of placebo-treated patients. Mean annual healthcare costs were SEK 137,752 (USD 16,438) per patient for the donepezil group and SEK 135,314 (USD 16,147) in the placebo group. With the average annual cost of donepezil at SEK 10,723 (USD 1,280) per patient, the SEK 2,438 (USD 291) cost difference represented a 77% cost offset. When caregiver time and healthcare costs were included, mean annual costs were SEK 209,244 (USD 24,969) per patient in the donepezil group and SEK 218,434 (USD 26,066) in the placebo group, a total saving associated with donepezil treatment of SEK 9,190 (USD 1,097) per patient [95% CI of SEK -43,959 (USD -5,246), SEK 25,581 (USD 3,053); p = 0.6]. The positive effects on the efficacy outcome measures combined with no additional costs from a societal perspective indicate that donepezil is a cost-effective treatment, representing an improved strategy for the management of patients with AD.     

多奈哌齐治疗轻中度阿尔茨海默病作用机制研究进展

多奈哌齐是第2代胆碱酯酶抑制剂,对轻中度阿尔茨海默病有较好疗效。近年关于多奈哌齐作用机制的相关研究较为丰富,本文拟就我国阿尔茨海默病诊断与治疗现状和多奈哌齐治疗轻中度阿尔茨海默病作用机制研究进展进行概述。     

Cost-effectiveness analysis of donepezil for mild to moderate Alzheimer's disease in Taiwan

BACKGROUND: Donepezil is a drug used for treatment in patients with Alzheimer's disease (AD). Information regarding the cost-effectiveness of this medication was previously rare in Asia. We used techniques of decision analysis and economic evaluation in conjunction with available local epidemiological and clinical data on costs of mild to moderate AD to assess the cost-effectiveness of donepezil in Taiwan. METHODS: A four-state Markov model was built to simulate the disease progression of AD patients. Local transition probabilities and costs of different stages were from the studies published earlier. RESULTS: Over a 5-year span, donepezil treatment for mild or moderate AD patients is predicted to result in the gain of 0.505 QALYs when comparing to usual care, while at the same time reducing the cost by US$7,691. The incremental cost was US$3,647 from the payer perspective; thus, the incremental cost-effectiveness ratio was estimated to be US$7,226 when considering only the medical expenditures. CONCLUSIONS: Under some assumptions, donepezil treatment might be a cost saving strategy for mild to moderate AD patients in Taiwan from a societal perspective. It is inconclusive from the payer's part since we still lack a consensus for judging the cost-effectiveness of a new health care technology.     

Increased levels of adrenocortical and gonadal hormones in mild to moderate Alzheimer's disease

Hormonal changes during normal aging include decreasing levels of gonadal hormones and adrenal androgens. These hormones influence multiple nervous functions, including cognition and mood. Related to this, abnormalities at several levels of the hypothalamic-pituitary-adrenal axis (HPA) have been reported in patients with Alzheimer's disease (AD). We studied steroid hormones in 33 patients with mild to moderate AD (12 men; 21 women, 76.4 +/- 7.8 years) and 22 healthy elderly controls (10 men; 12 women, 75.4 +/- 7.5 years old, respectively). Basal levels of serum cortisol, dehydroepiandrosterone (DHEA) and androstenedione were significantly increased in AD patients. Women with AD had significantly higher levels of DHEA and androstenedione. Serum estradiol levels were non-significantly increased in women with AD. After adjustment for age and BMI women with AD had significantly increased levels of androstenedione and DHEA. Increased gonadal hormone levels in mild to moderate AD may reflect an increased secretion, and/or alterations in metabolism of these hormones. This may influence the symptomatology and progression of the disease.