Pharmacological treatment of Alzheimer's Disease

BACKGROUND AND AIMS: The treatment of Alzheimer's disease (AD) is a challenge for physician, families, and patients. An individualized, multimodal treatment plan addressing the treatment of cognitive, behavioural and functional decline is essential. Aim of the paper is to describe the principal components of the treatment plan of AD patients. METHODS: A review of the recent literature was performed. RESULTS: Acetylcholinesterase inhibitors (AChEIs) play an important role in the improvement of cognitive decline in mild to moderate AD, even if the improvement is not permanent. Data obtained from the CRONOS project (involving about 500 Alzheimer Evaluation Units) replicate in the real world those obtained in controlled trials, confirming that AD patients may benefit from AChEI treatment. Treatment of behavioral and psychological symptoms of dementia (BPSD) requires education of caregivers, non pharmacological interventions, identification and treatment of medical illnesses or environmental precipitating conditions, specific pharmacological treatment. Traditional neuroleptics are widely used for BPSD treatment, but limited data support their use, and side-effects are frequent and severe. Atypical antipsychotics are effective in treating BPSD, and safer than traditional neuroleptics. However, the increased risk of cerebrovascular accident in patients taking risperidone or olanzapine limited currently their use in demented subjects. The use of antidepressant drugs, as well as behavioral approach, may improve depressive symptoms frequently accompanying AD. CONCLUSIONS: Although at present there is no cure for AD, several drug treatments and care strategies may improve or stabilize cognitive and behavioral symptoms, and improve the quality of life of patients and families.     

Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on caregiver burden

OBJECTIVES: This study investigated the efficacy of donepezil treatment on activities of daily living (ADLs) and social functioning in patients with moderate to severe Alzheimer's disease (AD) and the possible benefits of this treatment on caregiving time and stress levels. DESIGN: Randomized, double-blind, placebo-controlled, multinational study. SETTING: Patients resided in the community or in assisted living facilities who did not require skilled 24-hour nursing care. PARTICIPANTS: Two hundred ninety patients with moderate to severe AD (baseline standardized Mini-Mental State Examination score of 5-17). INTERVENTION: Donepezil (5 mg/d for 4 weeks and 10 mg/d per clinician's judgment thereafter) or placebo for 24 weeks. MEASUREMENTS: ADLs were assessed using the Disability Assessment for Dementia (DAD), the modified instrumental activities of daily living (IADL) scale (IADL+), and the modified Physical Self Maintenance Scale (PSMS+). Caregiver time spent assisting patients with basic and instrumental ADLs was recorded as part of the IADL+ and PSMS+ scales. Patients' social behavior was evaluated through the use of a caregiver diary that captured observations of patients' motivation, interactions, and engagement. Caregivers were evaluated for their levels of caregiver stress with a modified, multiple-item Caregiver Stress Scale (CSS). For each outcome measure, the mean change from baseline at Week 24 using a last observation carried forward (LOCF) analysis was calculated. RESULTS: IADL+ and PSMS+ mean change from baseline scores for donepezil-treated patients showed a slower decline during the study than placebo-treated patients (Week 24 LOCF mean treatment differences: IADL+ = 6.83, P <.0001; PSMS+ = 1.32, P =.0015). Significant differences between the groups in favor of donepezil were observed on the DAD for instrumental and basic ADLs and on the three components required for the completion of each ADL: initiation, planning and organization, and effective performance. At baseline, caregivers of patients treated with donepezil (n = 141) did not differ significantly from caregivers of patients treated with placebo (n = 146) with respect to demographics or mean total scores on the CSS. At Week 24 LOCF, the overall distribution of caregiver ratings on each of the three caregiver diary items favored donepezil-treated patients over placebo-treated patients (P <.005). At Week 24 LOCF, mean change from baseline scores for CSS total and individual domain scores (all domains except caregiving competence, personal gain, and management of distress) were better for caregivers of donepezil-treated patients than for those of placebo-treated patients (CSS total, mean treatment difference = 1.82). Caregivers of donepezil-treated patients reported spending less time assisting with ADLs than caregivers of placebo-treated patients (mean difference = 52.4 min/d). CONCLUSION: Donepezil demonstrated a significantly slower decline than placebo in instrumental and basic ADLs in these patients with moderate to severe AD. The ADL benefits in AD patients treated with donepezil were associated with less caregiving time and lower levels of caregiver stress.     

Behavioral and psychological symptoms, cognitive impairment and caregiver burden related to Alzheimer's disease patients treated in an outpatient memory clinic

AIM: The relationships among behavioral and psychological symptoms of dementia (BPSD), cognitive impairment of Alzheimer's disease (AD) patients and the caregiver burden of their caregivers were investigated in an outpatient memory clinic. METHODS: Forty-six pairs of AD patients and their family caregivers were involved in this study. Neuropsychiatry Inventory (NPI) was used to estimate BPSD, to which memory symptoms were added as a subcategory of BPSD. MMSE, word fluency, clock drawing test and category-cued memory test were used for cognitive measurement. Zarit burden interview (ZBI) and CES-D were used to assess caregiver burden. RESULTS: Among 11 BPSD subcategories, memory symptoms, apathy, depression, delusion, aggression and anxiety were prevalent BPSD was a strong determinant of caregiver burden. Among BPSD symptoms, anxiety, aggression and aberrant motor behavior were significantly related to ZBL In terms of the relationship between BPSD and cognitive impairment, the scores for delusion and apathy were significantly related to the cognitive decline. On the other hand, patients who showed symptoms related to memory and depression had higher cognitive function than those who did not. CONCLUSION: These analyses will contribute to better assessment of AD patients and their caregivers, hopefully resulting in better support for them.     

老年期痴呆的精神行为症状及美金刚的临床疗效研究

目的探讨老年期痴呆患者精神行为症状及美金刚的改善作用。方法选择老年期痴呆有精神行为症状的患者61例,随机分为2组,美金刚组(美金刚+多奈哌齐+尼莫地平)31例,对照组(多奈哌齐+尼莫地平)30例,分别在治疗前和治疗12周后进行简易智能状态检查量表(MMSE)、临床痴呆程度量表(CDR)及神经精神科问卷(NPI)的评估。结果老年期痴呆患者精神行为症状多见。美金刚组与对照组患者治疗前MMSE、CDR及各项症状的NPI评分差异无统计学意义(P>0.05)。美金刚组患者治疗12周后激越/攻击行为、焦虑、易激惹/不稳定性、情感高涨/欣快、夜间行为异常、食欲进食改变的NPI评分及NPI总分明显改善;对照组患者治疗12周后易激惹/不稳定性、夜间行为异常、食欲进食改变的NPI评分及NPI总分明显改善,差异有统计学意义(P<0.05)。美金刚组患者治疗12周后MMSE评分、激越/攻击行为、易激惹/不稳定性、食欲进食改变的NPI评分及NPI总分较对照组明显改善(P<0.05)。结论美金刚能有效改善老年期痴呆精神行为症状,减轻家庭负担。     

Use of serum insulin-like growth factor-I levels to predict psychiatric non-response to donepezil in patients with Alzheimer's disease.

OBJECTIVE: Insulin-like growth factor-I (IGF-I) deficiency may be involved in cognitive deficits seen with aging and in neurodegenerative diseases such as Alzheimer's disease (AD). This study was aimed at investigating whether non-responder to donepezil could be predicted using decreased serum levels of IGF-I in AD patients. DESIGN: This study involved 106 elderly subjects: 50 patients with AD and 56 age-matched controls without dementia. In patients with AD, donepezil was given orally 3 mg/day for 4 weeks and 5 mg/day for another 12 weeks. AD patients were divided into responders and non-responders based on the changes in mini-mental state examination (MMSE) scores before and 16 weeks after treatment with donepezil. Serum levels of IGF-I and atherogenic biomarkers were determined. RESULTS: Before treatment with donepezil, there was a significant positive correlation between serum IGF-I levels and the MMSE scores in all subjects. Serum IGF-I levels and the MMSE scores were significantly lower in AD patients than in non-demented controls and were the lowest in non-responders to donepezil. Atherogenic biomarkers (LDL cholesterol, triglycerides, lipoprotein(a), lipid peroxide, apolipoprotein E, and glucose levels) did not differ significantly among these groups. On multiple logistic regression, non-responders to donepezil showed decreased serum IGF-I levels <110 ng/ml and MMSE scores <15 points before treatment. CONCLUSIONS: These findings suggest that decreased levels of serum IGF-I combined with MMSE scores before treatment could predict non-responders to donepezil among AD patients, which may be a simple and practical method for selecting patients expected to show a response to treatment.     

Behavioral and psychologic symptoms in Alzheimer's disease: results of the REAL.FR study

Behavioral and Psychological Signs and Symptoms of Dementia (BPSD) are important manifestations of Alzheimer's Disease (AD) and other forms of dementia, because they are associate with care-giver distress, increase the likelihood of institutionalization, and may be associated with more rapid cognitive decline In this study (REAL.FR for Réseau sur la maladie d'Alzheimer Fran?ais) we prospectively used the Neuropsychiatric Inventory NPI to examine BPSD. 255 AD patients with a Mini-Mental State Examination (MMSE) score between 11 and 20 and 244 AD patients with a MMSE between 21 and 30 were examined. Factor analysis was carried out leading to three different syndromes according to the level of cognitive impairment. BPSD were detected in 92.5% of the patients with a MMSE between 11 and 20, and in 84% of the patients with a MMSE between 21 and 30. Apathy was the most common abnormality, followed by anxiety and dysphoria. These results in a French cohort of patients with AD underline the importance of the evaluation and finally of the treatment of BPSD.     

Donepezil is associated with delayed nursing home placement in patients with Alzheimer's disease

OBJECTIVES: To assess the relationship between donepezil treatment and time to nursing home placement (NHP) for patients with Alzheimer's disease (AD). DESIGN: Observational follow-up of patient NHP and vital status. SETTING: Community. PARTICIPANTS: Patients previously enrolled in one of three randomized, double-blind, placebo-controlled clinical trials of donepezil and two subsequent open-label studies (total N = 1,115); 671 patients provided complete data for analysis. MEASUREMENTS: Data were obtained through follow-up interviews with caregivers and chart reviews of patients with AD. Comparison groups were defined by whether patients received an effective dose of donepezil (>/=5 mg/d; >/=80% compliance) for specific numbers of weeks during the double-blind or open-label trial phase, in both phases, or in neither. Cox proportional hazards models were used to estimate risk ratios for NHP and survival curves from which median times to NHP were estimated for first dementia-related placement of longer than 2 weeks and permanent placement. The models were adjusted for age, sex, baseline Mini-Mental State Examination score, whether the caregiver was a spouse, caregiver continuity, and use of other cholinesterase inhibitors after the clinical trials. RESULTS: Use of donepezil of 5 mg/d or more was associated with significant delays in NHP. A cumulative dose-response relationship was observed between longer-term sustained donepezil use and delay of NHP. When donepezil was taken at an effective dose for at least 9 to 12 months, conservative estimates of the time gained before NHP were 21.4 months for first dementia-related NHP and 17.5 months for permanent NHP. CONCLUSION: Use of donepezil by AD patients resulted in significant delays in NHP. Long-term use of donepezil may help AD patients live longer in community settings, with consequent personal, social, and economic benefits.     

Effects of rivastigmine on actigraphically monitored motor activity in severe agitation related to Alzheimer's disease: a placebo-controlled pilot study

Acetylcholinesterase inhibitors (AChEIs) are effective in the treatment of cognitive symptoms in Alzheimer's disease (AD). Because the behavioral and psychological symptoms of dementia (BPSD) have also been attributed to central cholinergic deficits, we examined whether the AChEI rivastigmine can reduce motor activity as measured in a rater-independent manner by wrist actigraphy in agitated AD patients. A total of 20 consecutive AD inpatients (13 females, 7 males, 80.4+/-9.1 years, S.D.) were included from our geriatric psychiatry unit, all of whom were exhibiting agitated behavior not attributable to delirium. Patients were assigned randomly and in a single-blinded fashion to rivastigmine 3mg or placebo for 14 days. Motor activity levels were monitored using an actigraph worn continuously on the wrist of the non-dominant hand. At the beginning and end of the study, patients were assessed using the Neuropsychiatric Inventory (NPI) and Nurses' Observation Scale for Geriatric Patients (NOSGER). Patients in the rivastigmine group exhibited less agitation than placebo recipients on the NPI-agitation subscale, but not on NOSGER. Actigraphic measurements showed a tendency towards reduced motor activity in the rivastigmine group. Because rivastigmine usually exerts its main effects after a longer period of time, the short-term effects seen in our study justify further controlled clinical trials examining the use of rivastigmine in BPSD by means of actigraphy.     

Economic evaluation of donepezil for the treatment of Alzheimer's disease in Canada.

BACKGROUND: Donepezil is a new drug recently approved in the United States and Canada for the treatment of Alzheimer's disease (AD). We estimated the cost-effectiveness of donepezil 5 mg daily as an adjunct to usual care in the management of persons with mild-to-moderate AD defined as a Mini-Mental Health State Examination (MMSE) score in the range 10 to 26. METHODS: Treatment effect data as MMSE change-over-baseline scores were obtained from a 30-week placebo-controlled trial of donepezil. MMSE scores beyond observed trial data were estimated using a Markov model with 10 cycles of 24 weeks based on the placebo MMSE progression observed in the trial. Data from AD subjects in the Canadian Study of Health and Aging were used to estimate costs of nursing home care, community services, medications, and caregiver time as a function of MMSE score. A clinic-based cohort study from Alberta was used to estimate the distribution of AD patients by MMSE score presenting for treatment. The effectiveness measure for the economic model was expected time (over 5 years) spent with nonsevere AD (MMSE > or = 10). RESULTS: Over 5 years of treatment, donepezil is predicted to reduce health care costs by CA$929 per patient but increase caregiver time costs by CA$48 per patient for an overall cost saving to society of CA$882 per patient. Patients not receiving donepezil are predicted to spend 2.21 years of the 5 years in nonsevere AD compared with 2.41 years for treated patients (a gain of just over 2 months). Sensitivity analysis reveals that cost savings per patient increase if more AD patients are assumed to survive to 5 years; however, if donepezil treatment continues when patients' MMSE score falls below 10, the incremental cost is higher for treatment at CA$1554 per patient. CONCLUSION: Based on the limited available data, our model predicts that the use of donepezil for mild-to-moderate AD in Canada is associated with lower 5-year costs and less time spent with severe AD when compared with the alternative of usual care with no donepezil therapy. As more reliable long-term data become available, these predictions should be confirmed and/or updated.     

Early Statin Use and the Progression of Alzheimer Disease: A Total Population-Based Case-Control Study

The protective effect of statin on Alzheimer disease (AD) is still controversial, probably due to the debate about when to start the use of statin and the lack of any large-scale randomized evidence that actually supports the hypothesis. The purpose of this study was to examine the protective effect of early statin use on mild-to-moderate AD in the total Taiwanese population.This was a total population-based case-control study, using the total population of Taiwanese citizens seen in general medical practice; therefore, the findings can be applied to the general population. The study patients were those with newly diagnosed dementia (ICD-9 290.x) and prescribed any acetylcholinesterase inhibitors (AChEI) from the Taiwan National Health Insurance dataset in 1997 to 2008. The newly diagnosed eligible mild-to-moderate AD patients were traced from the dates of their index dates, which was defined as the first day to receive any AChEI treatment, back to 1 year (exposure period) to categorize them into AD with early statin use and without early statin use. Early statin use was defined as patients using statin before AChEI treatment. Alzheimer disease patients with early statin use were those receiving any statin treatment during the exposure period. Then, we used propensity-score-matched strategy to match these 2 groups as 1:1. The matched study patients were followed-up from their index dates. The primary outcome was the discontinuation of AChEI treatment, indicating AD progression.There were 719 mild-to-moderate AD-paired patients with early statin use and without early statin use for analyses. Alzheimer disease progression was statistically lower in AD patients with early statin use than those without (P = 0.00054). After adjusting for other covariates, mild-to-moderate AD patients with early stain use exhibited a 0.85-risk (95% CI = 0.76–0.95, P = 0.0066) to have AD progression than those without.Early statin use was significantly associated with a reduction in AD progression in mild-to-moderate AD patients. The future randomized trial studies can confirm our findings.     

Alzheimer's Disease: Current Pharmacotherapy in the Context of Patient and Family Needs

The objective of this paper is to review current evidence and treatment patterns for pharmacotherapy in Alzheimer's disease (AD), with an emphasis on outcomes considered important to patients and families. The sources for the information are the peer-reviewed literature, Food and Drug Administration-approved package labeling for acetylcholinesterase inhibitors (AChEIs), expert opinions expressed at the First Annual Dementia Congress, and clinical experience. Three AChEI agents are in routine use in the United States. They are considered part of the standard of care for patients with mild-to-moderate AD. There are differences in metabolism, pharmacokinetics, side effects, and ease of use that may influence the prescriber's choice of agent and dosage. The three approved agents have similar outcomes in cognition and global clinician ratings of effectiveness in double-blind placebo controlled trials. Persistent therapy with effective doses of AChEIs is associated with reduced risk for, or delayed, nursing home placement, which is a stated priority of AD caregivers. Agents from this class of drugs have also been shown to be associated with statistically significant preservation of daily function and benefits in treatment of adverse behaviors in AD. Numerous additional choices are available to the clinician for pharmacotherapy of adverse behaviors. Community-based psychoeducational support is also of value to caregivers.     

多奈哌齐治疗阿尔茨海默病的系统评价

目的 Meta分析评价多奈哌齐治疗阿尔茨海默病(AD)的临床疗效和安全性。方法计算机检索Medline、EMBASE、Ovid、CNKI及万方数据库。以AD患者服用多奈哌齐5mg和10mg口服干预12~30周为标准,以安慰剂为对照,选取自各数据库建库至2013年9月,筛选符合纳入标准的所有文献,并进行Meta分析。结果共检索到198篇相关文献,9篇随机对照试验文献符合纳入标准,AD患者共3064例。多奈哌齐对AD患者总体功能评价的改善效果均优于安慰剂(OR=1.86,95%CI:1.56~2.21,P<0.01)。与5mg治疗比较,多奈哌齐10mg治疗对AD患者总体功能评价的改善效果差异无统计学意义(OR=0.91,95%CI:0.72~1.15,P=0.43)。多奈哌齐的严重不良事件发生率与安慰剂比较,差异无统计学意义(OR=1.04,95%CI:0.88~1.24,P=0.65)。多奈哌齐5mg、10mg治疗AD的严重不良事件发生率比较,差异无统计学意义(OR=0.70,95%CI:0.47~1.04,P=0.08)。结论多奈哌齐可显著改善AD患者的总体功能评价,安全性好,但疗效并不存在剂量依赖性。但限于纳入的研究文献较少及疗法学质量上的局限,本系统评价结果尚需更多高质量的随机对照试验进一步验证。     

阿尔茨海默病患者精神行为症状与照料者负担的相关性分析

目的分析阿尔茨海默病(AD)患者精神行为症状(BPS)的临床特点与照料者负担的关系。方法连续纳入江苏省苏北人民医院2015年11月~2017年11月确诊的AD患者43例及其照料者,采用简易智能状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)和认知障碍简明评价量表(Cog-12)评估AD患者的认知功能;采用神经精神量表问卷(NPI-Q)评估AD患者BPS;采用照料者负担量表(CBI)评估照料者负担,并进行Pearson相关性分析。结果入选的AD患者MMSE总分(17.3±5.9)分,MoCA总分(13.1±6.4)分,Cog-12总分(24.3±10.6)分,NPI-Q评估患者BPS总严重程度为(2.51±2.26)分;照料者总苦恼程度为(3.23±3.07)分,AD患者照料者的CBI总分为(24.70±13.34)分。NPI-Q评估AD患者BPS严重程度和照料者苦恼程度总分与MMSE评分和MoCA及Cog-12总分不相关(P>0.05)。NPI-Q评估AD患者BPS严重程度总分与时间依赖负担、社交负担、情感负担、CBI总分呈正相关(r=0.439,0.330,0.319和0.386,P<0.05);NPI-Q评估BPS照料者苦恼程度总分与时间依赖负担和CBI总分呈正相关(r=0.417和0.306,P<0.05)。结论AD患者BPS增加照料者的时间依赖负担、社交负担及情感负担。     

IL-4 in vitro production is upregulated in Alzheimer's disease patients treated with acetylcholinesterase inhibitors

Cytokines appear to be involved in the pathogenesis of Alzheimer's Disease (AD). Their modulation by treatment has been investigated only in a few studies. The aim of our study was to evaluate the effect of acetylcholinesterase inhibitors (AChEI) on Interleukin-4 (IL-4) production in AD patients. IL-4 levels were measured by ELISA on peripheral blood mononuclear cell cultures in the presence or absence of Concanavalin A or Phytohaemagglutinin. Linear regression analysis shows that patients who have been treated, have higher levels of IL-4 independently from age, gender and comorbidity. The increased production of IL-4 in AChEI treated patients might represent an additional mechanism through which AChEI act on AD progression.     

Long-term cognitive benefits of donepezil in Alzheimer's disease: A retrospective comparison between 1994–1999 and 2000–2004

Objective:   In order to address an issue of how long Alzheimer's disease (AD) patients should receive donepezil, we estimated long-term effect of donepezil on cognition as well as its influential factors. We also evaluated the additional effect of cerebrospinal fluid (CSF)-tau protein levels on diagnosis.
Methods:   We compared cognitive changes between current (2000–2004) AD patients (donepezil users) and previous AD patients, seen by us 1994–1999, without receiving donepezil (non-donepezil users) by a mixed effect model. Cognition was assessed by Mini-Mental State Examination (MMSE) at 6-month intervals up to 24 months. Sensitivity analysis was performed exclusively on patients with high CSF-tau protein levels (CSF-tau >330 pg/mL) to minimize inaccuracies of the diagnosis
Results:   From 495 AD patients reviewed, 192 patients (120 donepezil users and 72 controls) were eligible. Estimated annual decline of MMSE was 1.2 points (95% confidence interval (95%CI), 0.9–1.5) in the donepezil users, whereas it was 2.8 points (95%CI, 2.1–3.6) in the control group. The difference was statistically significant ( P  < 0.001). The sensitivity analysis demonstrated that these declines were 1.2 (95%CI, 0.8–1.6) and 3.1 (95%CI, 2.3–3.9) points in the donepezil users and control groups, respectively.
Conclusions:   Long-term donepezil use for at least 2 years appeared to be beneficial in maintaining cognition in AD patients. As the cholinergic central nervous system consistently degenerates over time, long-term use of donepezil may be an appropriate therapy. Discontinuation of donepezil may not be recommended as far as patients are in a stable condition.     

Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: A meta-analysis

Objective

To determine the efficacy of cholinesterase inhibitors (ChEIs) in improving the behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer’s disease (AD).

Data sources

We searched MEDLINE, Cochrane Registry, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1966 to 2007. We limited our search to English Language, full text, published articles and human studies.

Data extraction

We included randomized, double-blind, placebo-controlled trials evaluating the efficacy of donepezil, rivastigmine, or galantamine in managing BPSD displayed by AD patients. Using the United States Preventive Services Task Force (USPSTF) guidelines, we critically appraised all studies and included only those with an attrition rate of less than 40%, concealed measurement of the outcomes, and intention to treat analysis of the collected data. All data were imputed into pre-defined evidence based tables and were pooled using the Review Manager 4.2.1 software for data synthesis.

Results

We found 12 studies that met our inclusion criteria but only nine of them provided sufficient data for the meta-analysis. Among patients with mild to severe AD and in comparison to placebo, ChEIs as a class had a beneficial effects on reducing BPSD with a standard mean difference (SMD) of −0.10 (95% confidence interval [CI]; −0.18, −0.01) and a weighted mean difference (WMD) of −1.38 neuropsychiatry inventory point (95% CI; −2.30, −0.46). In studies with mild AD patients, the WMD was −1.92 (95% CI; −3.18, −0.66); and in studies with severe AD patients, the WMD was −0.06 (95% CI; −2.12, +0.57).

Conclusion

Cholinesterase inhibitors lead to a statistical significant reduction in BPSD among patients with AD, yet the clinical relevance of this effect remains unclear.     

The effect of a family therapy and technology-based intervention on caregiver depression

PURPOSE: The majority of persons with Alzheimer's disease (AD) are cared for at home by a family member such as a spouse or daughter. Caregiving places enormous demands on these caregivers, and the negative consequences associated with caregiving are well documented. This paper reports results from the Miami site of the REACH (Resources for Enhancing Alzheimer's Caregiver Health) program that examined the efficacy of a family therapy and technology-based intervention in reducing depressive symptoms (according to the Center for Epidemiological Studies Depression scale) among family caregivers of AD patients at 6 months and 18 months follow-up. DESIGN AND METHODS: There were 225 White American and Cuban American caregivers that were randomized into a structural ecosystems therapy, structural ecosystems therapy + computer-telephone integrated system, or minimal support control condition. RESULTS: Caregivers in the combined family therapy and technology intervention experienced a significant reduction in depressive symptoms at 6 months. The 18-month follow-up data indicated that the intervention was particularly beneficial for Cuban American husband and daughter caregivers. IMPLICATIONS: The results indicate that information technology has a promising role in alleviating distress and depression among groups of AD caregivers. The data also demonstrate that interventions have differential impacts according to ethnic group and the caregiver-patient relationship.     

阿尔茨海默病患者出现精神行为症状的相关因素分析

目的 探讨阿尔茨海默病（AD）患者出现精神行为症状（BPSD）的相关因素。方法 对门诊和住院的155例符合精神障碍诊断与统计手册第4版（DSM-IV）诊断标准的AD患者，进行自制调查表、AD病理行为评分表（BEHAVE-AD）、痴呆行为量表（DBD）评定。结果 AD患者BPSD的相关因素分析发现：（1）AD患者DBD总分、BEHAVE-AD及妄想总分均与AD患者性格、年龄、婚姻状况及发病年龄相关，行为紊乱总分与患者的年龄、婚姻状况、性格相关，情感障碍与性格、发病前的生活事件及病程相关，焦虑恐惧与AD患者发病前的生活事件及病程相关，节律紊乱与性格和嗜好相关，攻击行为与婚姻状态及性格有关；（2）线性回归分析发现性格、婚姻状况对DBD与BEHAVE-AD总分有较大的影响。结论 AD患者BPSD的相关因素有年龄、性格、婚姻状况、嗜好、发病前生活事件、发病年龄、AD病程等；关系较为密切的有：性格、婚姻状况；推测外向性格和婚姻不稳定有可能是AD患者出现BPSD的危险因素。     

多奈哌齐和石杉碱甲治疗老年人轻度认知功能障碍的疗效对比研究

目的 研究多奈哌齐和石杉碱甲治疗老年轻度认知功能障碍(MCI)患者的疗效.方法 122例老年MCI患者分为两组:多奈哌齐组71例患者和石杉碱甲51例患者,多奈哌齐组予口服多奈哌齐5.0 mg,1次/d;石杉碱甲组口服石杉碱甲0.1 mg,2次/d.所有患者随访24周,用药前、用药12周及24周后分别进行认知功能的评定,包括简易智能状态量表检查(MMSE)、蒙特利尔认知评估(北京版)量表(MOCA)、阿尔茨海默病评定量表-记忆分量表(ADAS-cog)、临床痴呆量表(CDR)、总体衰退量表(GDS)、日常生活能力量表(ADL)、Hachinski缺血指数评分(HIS)和汉密尔顿抑郁量表(HAMD).结果 两组患者年龄、性别、受教育年限、用药前神经心理学量表评分差异均无统计学意义.与用药前比较,多奈哌齐组患者用药12周、24周后,MMSE评分均明显升高(t=4.47、6.16,均P＜0.01),ADAS-cog明显降低(t=2.33、3.68,均P＜0.05);与用药前比较,多奈哌齐组患者用药24周后MOCA评分明显升高(t=2.56,P＜0.05).石杉碱甲组用药24周后,MMSE评分较用药前明显升高(t=2.80,P＜0.05),石杉碱甲组用药后12周、24周MOCA、ADAS-cog评分与用药前比较差异均无统计学意义.用药24周后两组比较,多奈哌齐组患者MMSE评分较石杉碱甲组明显升高(t=2.01,P＜0.05),ADAS-cog较石杉碱甲组降低(t=2.09,P＜0.05).多奈哌齐组治疗有效30例,总有效率42.3％,石杉碱甲组治疗有效9例,总有效率17.6％,两组有效率比较差异有统计学意义(x2 =8.26,P＜0.01).多奈哌齐组5例、石杉碱甲组3例患者出现轻微不良反应,继续用药或调整用药时间后消失.结论 在老年MCI患者的治疗中,乙酰胆碱酯酶抑制剂多奈哌齐和石杉碱甲均安全有效,且多奈哌齐起效较石杉碱甲更快,作用更明显.