Robert P-H, Schuck S, Dubois B, Lépine J-P, Gallarda T, Olié J-P, Goni S, Troy S
Centre Mémoire de Ressources et de Recherches - PACA, CHU, Nice.
Encephale. 2003 May-Jun;29(3 Pt 1):266-72.
Alzheimer's disease (AD) is a major healthcare challenge due to the increasing longevity of the population. Clinically prominent neuropsychological and neurological impairments, together with behavioral disorders characterize Alzheimer's disease (AD). In the past, behavioural and emotional disturbances received less attention than cognitive symptoms in studies of dementia. The association between cognitive and behavioural symptoms is complicated by the fact that such association could also occur with different patterns during depressive episode without dementia. Because Alzheimer's disease (AD) tends to be under diagnosed, there is an increasing need for accurate neuropsychological screening tools that are easy to administer by psychiatrists. The aim of the present study was to validate, in French, a sensitive and specific screening battery (B2C) designed to improve the discrimination between patients with AD, patients with depression, and healthy elderly subjects.
The B2C was administered to 123 ambulatory subjects (mean age 76.4 2.3 years): divided in three groups of subjects. AD subjects were included (n=49) with a Mini-Mental Status Examination (MMSE) score of between 18 and 26, and a confirmed diagnosis (DSM IV) of mild to moderate AD. Subjects were not included if they were receiving treatment with an acetylcholinesterase inhibitor. The depressive group comprised elderly subjects (n=27) with at least two DSM IV criteria for a major depressive episode including the depressive mood criterion and a score of more than 17 on the Montgomery-Asberg Depression Rating Scale (MADRS). The healthy control group (n=47) comprised age-matched subjects with no neurological or psychiatric pathology. The B2C consists of four individual tasks derived from classical neuropsychological tests. Tasks were presented in the following order: temporal orientation test (knowledge of month, date, year, day of the week and time of day), 5 word test (task is originally derived from the Enhanced Cued Recall test), clock drawing test (In this widely used test, the subject had to draw a clock with all the numbers and then draw the clock hands at twenty minutes to four), and the semantic verbal fluency test (the subject was asked to generate as many words as possible from a given category in a fixed time period of 60 seconds). During the pre-study investigator meeting, the test procedure was adapted to ensure uniformity of practice in all centres. The B2C was administered one week to one month after the study inclusion date by a psychologist blinded to the patient groups and who had not participated in the subject's inclusion. Multivariate analysis was performed using a forced model of all four tests. Due to the nature of the dependent variable (AD vs controls and depressive vs control), the chosen discrimination model was a binary logistical regression model. Explanatory variables were limited to the variables of the test battery, and the dependent variable was the subject's status (AD, depressive or control).
The mean results for each test are presented in Table II. The time taken to perform the tests was significantly higher (p=0.0001) for the AD group (11.2 minutes) when compared with both the control (7.6 minutes) and depressive group (8.2 minutes). In each of the four subtests, the AD subjects were significantly more impaired than the two other groups. Multivariate analysis was performed using a forced model of all four tests which provided correct classification of a high percentage of subjects (88.5%). The analysis followed a normal distribution and demonstrated that the AD patients were significantly impaired in all four tests of the B2C compared with controls. Depressive, elderly subjects were only impaired in verbal fluency. Multivariate analysis showed that, compared with controls, patients with mild AD were significantly impaired for all four tests. Response operating characteristics (ROC) analysis of the B2C showed: 93.8% sensitivity and 85% specificity for discriminating AD from control patients (table III), and 63% sensitivity and 96% specificity for discriminating AD from depressive patients (table IV).
The main objective of this study was to demonstrate that the Short Cognitive Evaluation Battery developed in the French language is able to discriminate between patients suffering from AD and healthy elderly subjects. The results clearly demonstrate that AD patients were significantly impaired in all four tests of the B2C compared with the control group. The present study also supports the use of the screening battery for discriminating between AD and depressive subjects. The SCEB was less discriminatory for AD versus depressive patients than for AD versus controls. This could be due to the limited size of the depressive group. The verbal fluency test was the most sensitive for discriminating between AD and depression but this was at the expense of specificity. Other brief screening tests have already been developed in English speaking countries, In French language, the B2C appears to be a highly sensitive and specific tool for discriminating between patients with mild AD and healthy elderly individuals. Furthermore, in combination with clinical evaluation, the B2C could improve the specificity of the difficult discrimination between mild AD and depression. The next step of the validation process will include concurrent validity study and inclusion of a higher number of subjects with depressive symptoms.
由于人口寿命的延长,阿尔茨海默病(AD)成为一项重大的医疗保健挑战。临床上显著的神经心理学和神经学损伤,以及行为障碍是阿尔茨海默病(AD)的特征。过去,在痴呆症研究中,行为和情绪障碍受到的关注少于认知症状。认知和行为症状之间的关联很复杂,因为这种关联在无痴呆症的抑郁发作期间也可能以不同模式出现。由于阿尔茨海默病(AD)往往诊断不足,越来越需要准确且易于精神科医生实施的神经心理学筛查工具。本研究的目的是用法语验证一种敏感且特异的筛查组合测试(B2C),旨在提高对AD患者、抑郁症患者和健康老年受试者的鉴别能力。
对123名门诊受试者(平均年龄76.4±2.3岁)进行了B2C测试,这些受试者分为三组。纳入AD受试者(n = 49),其简易精神状态检查表(MMSE)得分在18至26之间,且确诊为轻度至中度AD(DSM-IV)。如果受试者正在接受乙酰胆碱酯酶抑制剂治疗,则不纳入。抑郁组包括老年受试者(n = 27),他们至少符合两项DSM-IV中重度抑郁发作的标准,包括抑郁情绪标准,且蒙哥马利-阿斯伯格抑郁评定量表(MADRS)得分超过17分。健康对照组(n = 47)由年龄匹配且无神经或精神疾病的受试者组成。B2C由四项源自经典神经心理学测试的单独任务组成。任务按以下顺序呈现:时间定向测试(对月份、日期、年份、星期几和一天中的时间的知晓)、5个单词测试(该任务最初源自增强线索回忆测试)、画钟测试(在这个广泛使用的测试中,受试者必须画出一个标有所有数字的时钟,然后在差二十分钟四点时画出时钟指针)和语义言语流畅性测试(要求受试者在60秒的固定时间段内从给定类别中尽可能多地生成单词)。在研究前的研究者会议上,对测试程序进行了调整,以确保所有中心的操作一致性。B2C在研究纳入日期后一周至一个月内,由对患者分组不知情且未参与受试者纳入过程的心理学家进行测试。使用所有四项测试的强制模型进行多变量分析。由于因变量的性质(AD与对照组以及抑郁组与对照组),所选的鉴别模型是二元逻辑回归模型。解释变量限于测试组合的变量,因变量是受试者的状态(AD、抑郁或对照)。
每项测试的平均结果列于表II。与对照组(7.6分钟)和抑郁组(8.2分钟)相比,AD组完成测试所需时间显著更长(p = 0.0001)(11.2分钟)。在四个子测试中的每一项中,AD受试者的受损程度均显著高于其他两组。使用所有四项测试的强制模型进行多变量分析,该模型对高比例的受试者(88.5%)进行了正确分类。分析呈正态分布,表明与对照组相比,AD患者在B2C的所有四项测试中均显著受损。抑郁的老年受试者仅在言语流畅性方面受损。多变量分析表明,与对照组相比,轻度AD患者在所有四项测试中均显著受损。B2C的反应操作特征(ROC)分析显示:区分AD与对照患者时,敏感性为93.8%,特异性为85%(表III);区分AD与抑郁患者时,敏感性为63%,特异性为96%(表IV)。
本研究的主要目的是证明用法语开发的简短认知评估组合测试能够区分AD患者和健康老年受试者。结果清楚地表明,与对照组相比,AD患者在B2C的所有四项测试中均显著受损。本研究还支持使用该筛查组合测试来区分AD和抑郁受试者。B2C对AD与抑郁患者的鉴别能力比对AD与对照患者的鉴别能力弱。这可能是由于抑郁组规模有限。言语流畅性测试在区分AD和抑郁方面最敏感,但这是以牺牲特异性为代价的。在英语国家已经开发了其他简短筛查测试,在法语中,B2C似乎是区分轻度AD患者和健康老年个体的高度敏感且特异的工具。此外,结合临床评估,B2C可以提高轻度AD和抑郁之间难以鉴别的特异性。验证过程的下一步将包括同时效度研究,并纳入更多有抑郁症状的受试者。