多奈哌齐联合养血清脑颗粒改善轻度认知功能障碍的效应

目的评价多奈哌齐联合养血清脑颗粒对轻度认知功能障碍患者的疗效。方法30例轻度认知功能障碍患者随机分为多奈哌齐组14例;多奈哌齐联合养血清脑颗粒16例,共服用16周。分别测定两组治疗前后简易智力状态量表(MMSE)总分及成人韦氏记忆测验记忆商(MQ);经颅多普勒(TCD)检查评估两组治疗前后的脑血流参数改变。结果(1)治疗前多奈哌齐组及多奈哌齐联合养血清脑颗粒治疗组在MMSE的亚项记忆力和回忆力无显著差别(P>0.05);治疗16周后多奈哌齐组及多奈哌齐联合养血清脑颗粒治疗组在MMSE的亚项记忆力和回忆力上较治疗前有显著差别(P<0.05);(2)治疗前多奈哌齐组及多奈哌齐联合养血清脑颗粒治疗组在MQ的亚项图片回忆、再认及背数方面上无显著差别,治疗后多奈哌齐组及多奈哌齐联合养血清脑颗粒治疗组在亚项图片回忆、再认及背数方面较治疗前均有提高;联合治疗组更为显著。(3)治疗前TCD检测两组患者均可显示双侧脑血流不对称、血管阻力指数增高,治疗后自身对照脑血流趋于对称,血管阻力指数降低,多奈哌齐联合养血清脑颗粒组改变明显(P<0.05),多奈哌齐组无显著改善(P>0.05)。结论多奈哌齐联合养血清脑颗粒对改善轻度认知功能障碍患者的记忆力及脑血流改善有明显疗效。     

多奈哌齐联合疏血通治疗老年性痴呆的疗效分析

目的：探讨老年性痴呆患者在联合服用多奈哌齐和疏血通后对认知和行为功能的临床疗效。方法把本院抽取的100例老年性痴呆患者随机平均分为两组,分别是对照组50例和试验组50例,对照组患者给予丹参注射液,试验组患者在服用多奈哌齐的同时,给予注射疏血通。观察并比较两组患者12个月后的简易智力状态检查量表（MMSE）评价和日常生活功能量表（ADL）评价,进行疗效统计。结果12个月后试验组的患者MMSL评分明显高于治疗前, ADL评分明显低于治疗前,与对照组相比改善比较明显,且试验组患者的治愈有效率为83.0%,明显高于对照组的65.0%, P〈0.05,差异具有统计学意义。结论老年性痴呆患者在同时给予多奈哌齐和疏血通治疗后,治疗效果、认知和行为功能明显得到改善,临床效果好于单用丹参注射液。     

Alzheimer's disease treated with combined therapy based on nourishing marrow and reinforcing Qi

OBJECTIVE:To study the efficacy and safety of combined Traditional Chinese Medicine(TCM) therapy based on nourishing marrow to improve intellect and reinforcing Qi to activate bloodon mild to moderate Alzheimer's disease(AD).METHODS:Sixty-six patients with AD,whoseMini-Mental State Examination(MMSE) score were from 10-24,were randomized equally into an intervention group and a control group.The control group was given Aricept(5 mg,once daily).The intervention group was further divided into Yang-Qi deficiency(n = 18) and of Yin-Qi deficiency(n = 15)subgroups.Patients in the Yang-Qi deficiency group were intravenously administered Shenfu injection,60 mL,and deproteinized calf blood injection(DCBl),1.2 g,once daily.The Yin-Qi deficiency group was given Shenmai injection,60 mL,and DCBl,1.2 g,once daily.Each course lasted 21 days.RESULTS:Compared with the control group and with pre-treatment in the same group,MMSE,clinical dementia rating,and activities of daily living scale scores in the intervention group were significantly improved(all P0.05).These metrics mildly improved in the control group compared with before treatment(P0.05).No adverse effects were observed in any group during treatment.CONCLUSION:We found that combined TCM therapy is effective and safe for managing mild to moderate AD.     

低频电刺激联合盐酸多奈哌齐治疗血管性痴呆的疗效观察

目的探讨低频电刺激联合盐酸多奈哌齐对血管性痴呆（VaD）患者的治疗效果。方法将64例确诊为血管性痴呆的患者随机分治疗组（33例）及对照组（3l例），2组患者均在常规内科处理基础上给予盐酸多奈哌齐口服治疗，治疗组患者同时于双侧乳突区加用低频电刺激干预。治疗前及治疗12周后分别采用简易精神状态痴呆量表（MMSE）、临床痴呆量表（CDR）及Barthel指数评分进行疗效判定。结果经12周治疗后，2组患者的MMSE和Barthel指数评分均显著增高，CDR评分明显下降（P〈0．05），且以治疗组患者的改善幅度更为显著，与对照组比较，差异具有统计学意义（P〈0．01）；同时治疗组患者的定向力、注意力及记忆力评分均显著增加（P〈0．05或0．01），而对照组患者仅有记忆力评分较治疗前改善显著（P〈0．05）。结论低频电刺激联合盐酸多奈哌齐治疗VaD患者疗效显著，患者经治疗后其总体认知功能、日常生活活动能力及记忆力均显著改善。     

多奈哌齐对急性一氧化碳中毒迟发性脑病患者认知功能的影响

目的观察多奈哌齐对急性一氧化碳中毒迟发性脑病(DEACMP)患者认知功能的影响。方法将80例DEACMP患者随机分成对照组(40例)和治疗组(40例)。对照组给予常规药物、安慰剂加高压氧治疗,治疗组给予常规药物、多奈哌齐加高压氧治疗,多奈哌齐剂量为每晚5.0 mg,连续治疗90 d为一疗程。采用MMSE及Barthel指数评定量表(BI)对患者的认知功能和日常生活能力进行评价,并进行组间比较。结果与治疗前比较,两组患者治疗后MMSE及BI评分均明显升高(P0.05~0.01)。治疗后治疗组MMSE及BI评分均明显高于对照组(P0.05~0.01)。结论多奈哌齐可明显改善DEACMP痴呆患者的认知功能及日常生活能力,值得临床推广。     

Role of Donepezil in the Management of Neuropsychiatric Symptoms in Alzheimer's Disease and Dementia with Lewy Bodies

Alzheimer's disease (AD) is a progressive condition that affects cognition, function, and behavior. Approximately 60–90% of patients with AD develop neuropsychiatric symptoms (NPS) such as hallucinations, delusions, agitation/aggression, dysphoria/depression, anxiety, irritability, disinhibition, euphoria, apathy, aberrant motor behavior, sleep disturbances, appetite and eating changes, or altered sexual behavior. These noncognitive behavior changes are thought to result from anatomical and biochemical changes within the brain, and have been linked, in part, to cholinergic deficiency. Cholinesterase inhibitors may reduce the emergence of NPS and have a role in their treatment. These agents may delay initiation of, or reduce the need for, other drugs such as antipsychotics. This article summarizes the effects of donepezil, a cholinesterase inhibitor, on the NPS of dementia with emphasis on AD and dementia with Lewy bodies.     

高压氧联合盐酸多奈哌齐治疗老年期痴呆临床研究

目的观察高压氧联合盐酸多奈哌齐治疗老年期痴呆（elderly dementia,ED）的临床疗效。方法 82例阿尔茨海默病（Alzheimer＇s disease,AD）和93例血管性痴呆（vascular dementia,VD）患者,随机分为高压氧、盐酸多奈哌齐、高压氧＋盐酸多奈哌齐、吡拉西坦组。比较治疗前后各组简易精神状态量表（MMSE）、韦氏成人记忆量表（WMS）、生活功能量表（ADL）的评分。结果治疗后高压氧、盐酸多奈哌齐、高压氧＋盐酸多奈哌齐组其MMSE、ADL、WMS评分均较治疗前明显改善,且均优于吡拉西坦对照组,高压氧＋盐酸多奈哌齐治疗组又优于单纯盐酸多奈哌齐组和高压氧治疗组。结论高压氧联合盐酸多奈哌齐应用可明显改善AD与VD患者的MMSE、WMS、ADL评分,疗效提高,值得临床进一步推广应用。     

交泰丸联合盐酸多奈哌齐治疗血管性痴呆45例临床研究

目的观察交泰丸联合盐酸多奈哌齐治疗血管性痴呆（vasculardementia,VD）的临床疗效。方法90例VD患者按随机数字表法随机分为两组,治疗组45例采用交泰丸0．02g／（kg·d）,2次／d,早晚饭后口服,同时予盐酸多奈哌齐5mg每晚临睡前口服,共治疗4周。对照组45例采用盐酸多奈哌齐5mg每晚临睡前口服,共治疗4周。观察治疗4周后的临床疗效,以及治疗4周后评价简易精神状况检查量表（MMSE）、日常生活能力（ADL）的变化。结果治疗组治疗后的显效率和总有效率均明显高于对照组（P〈0．05）;并且治疗组治疗后MMSE和ADL评分均明显高于对照组（P〈0．05）。结论交泰丸联合盐酸多奈哌齐治疗VD疗效显著,优于单独使用盐酸多奈哌齐。     

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.     

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.