阿尔茨海默病评估量表可能不够准确

英国普利茅斯大学临床神经研究组的Jeremy Hobart博士及其同事发现，阿尔茨海默病临床试验中最常用的认知表现检查可能过于简单，不足以准确评估患者认知能力的范围或发现认知能力随时间的改变(Alzheimers Dement. 2012 [doi:10.1016/j.jalz.2012.08.005])。

研究者从ADNI(阿尔辞海默病神经影像创新)研究中选取了193例受试者的资料，以评价ADAS-Cog(阿尔茨海默病评估量表-认知行为部分)评分是否仍有需要改进之处。受试者的平均年龄为74岁，47%为女性，平均Mini精神状态检查评分为23分。资料包括基线、6个月、12个月和24个月时675项指标的评分。

结果未发现可能限制量表识别低功能或高功能患者状态变化的总体效能的地板效应和天花板效应。但是，量表11个组分中有8个(例外的3个组分是单词回忆、单词识别和方向感)具有明显的天花板效应，评分呈偏态分布。

上述结果与Hobart博士等人此前对ADAS-Cog进行心理评估的结果一致(J. Neurol. Neurosurg. Psychiatry 2010;81:1363-8)。研究者称，这些结果意味着“这些组分可能低估了轻至中度阿尔茨海默病型痴呆症患者的认知表现差异”。

在ADNI研究中有超过3/4的轻度阿尔茨海默病受试者在ADAS-Cog的多数组分上得到0或1分，提示仅有极少数认知问题被发现。“目前的ADAS-Cog的检测精度不足以发现和监测最轻度阿尔茨海默病型痴呆症患者的认知改变。”

为了避免评估量表可靠性和准确性的经典方法的固有局限性，研究者还根据Rasch检测理论，采用数字模型对同一样本开展了另一项研究，以评估ADAS-Cog能够准确反映认知表现的评分范围。

结果显示，ADAS-Cog的11个组分中有6个因采用整数评分而不能反映出连续性改变，反而表明某些组分评分更易出现，这意味着某个组分的评分高并不能证明认知功能受损。

这2项研究均获得了一项匿名基金、英国国立卫生研究院和美国国立卫生研究院的资助。

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Portions of one of the most commonly used tests to measure cognitive performance in Alzheimer’s disease trials may be too easy and may not accurately assess the range of patients’ cognitive abilities or detect their change over time, according to two complementary studies.

Analyses of Alzheimer’s Disease Assessment Scale – Cognitive Behavior Section (ADAS-Cog) scores measured in 193 patients with mild disease who participated in ADNI (the Alzheimer’s Disease Neuroimaging Initiative) over the course of 2 years detected limitations of the scale that could be improved, reported Dr. Jeremy Hobart of the Clinical Neurology Research Group at Plymouth (England) University Peninsula Schools of Medicine and Dentistry, and his colleagues.

The investigators used observational data from ADNI to show that out of 675 measurements made at time points of 0, 6, 12, and 24 months, data from ADAS-Cog total scores spanned the entire range of the scale and had no floor or ceiling effects that would reduce its ability to measure changes and differences in lower-functioning or higher-functioning patients, respectively. However, 8 of the scale’s 11 components (all except for word recall, word recognition, and orientation) had statistically significant ceiling effects with a skewed distribution of scores (Alzheimers Dement. 2012 [doi:10.1016/j.jalz.2012.08.005]). The mean age of patients was 74 years, 47% were female, and participants had a mean Mini-Mental State Examination score of 23 across all time points.

These results reproduce those that the investigators obtained in a previous psychometric evaluation of the ADAS-Cog in patients who participated in a randomized, controlled clinical trial (J. Neurol. Neurosurg. Psychiatry 2010;81:1363-8). They noted that the results mean that "these components may underestimate cognitive performance differences in those with mild to moderate AD-type dementia. This may lead to problems in detecting clinical change."

Because often greater than three-fourths of the participants with mild Alzheimer’s disease in the ADNI study scored either 0 or 1 on the majority of ADAS-Cog components, Dr. Hobart and his associates remarked that this would mean that few or no cognitive problems were detected. "However, as there is almost certainly greater variance in patient ability, this finding points to a limitation in the ADAS-Cog score function – namely that the ADAS-Cog, in its current form, is not subtle enough to record and monitor variance in the mildest stages of AD-type dementia."

In a second study that analyzed the extent to which the ADAS-Cog accurately measured cognitive performance in the same sample of patients, the investigators tried to avoid the limitations imposed by classical means of assessing reliability and validity of scales. They did this by using a method called Rasch Measurement Theory, which is a mathematical model designed to analyze the extent to which the rating scale data meet certain conditions necessary for the scale to record accurate measurements of cognitive performance. It provides diagnostic information that can help to revise a scale by exposing anomalies in the scale that can be improved and then retested, Dr. Hobart and his colleagues explained.

The range of cognitive performance measured by the 11 ADAS-Cog components suboptimally targeted the range of cognitive performance observed in patients in the sample. In six of the components, the integer-based scoring method used to assign cognitive performance did not reflect a continuum of performance as it was intended to, but instead indicated that some component scores were much more likely to occur than others, meaning that a higher score on one of these components did not confirm more cognitive impairment.

These gaps in some of the components’ abilities to measure cognitive performance means that their precision is limited, and that the raw scores of the ADAS-Cog and the linear relationship they are thought to reflect is actually an S-shaped relationship in which a 1-point change in ADAS-Cog measurement varies across the range of the scale, such that it is highest at the extremes of the its range and lowest at the center of its range, the investigators said (Alzheimers Dement. 2012 [doi:10.1016/j.jalz.2012.08.006]).

Both studies were supported in part by grants from an anonymous foundation, the U.K. National Institute for Health Research, and the U.S. National Institutes of Health.

学科代码：神经病学 精神病学 老年病学　　　关键词：阿尔茨海默病 认知评估量表
来源： EGMN