阿尔茨海默病诊断病理确认中的谬误。
Fallacies in the pathological confirmation of the diagnosis of Alzheimer's disease.
作者信息
Bowler J V, Munoz D G, Merskey H, Hachinski V
机构信息
Department of Clinical Neurological Sciences, John P Robarts Research Institute, University of Western Ontario, London, Canada.
出版信息
J Neurol Neurosurg Psychiatry. 1998 Jan;64(1):18-24. doi: 10.1136/jnnp.64.1.18.
OBJECTIVE
Necropsy confirmed clinical diagnostic accuracy for Alzheimer's disease is claimed to exceed 90%. This figure contains two fallacies; it includes cases in which Alzheimer's disease exists with other diseases affecting cognition and the studies that report these figures excluded cases without necropsy (verification bias). The effect of these errors is estimated.
METHODS
Data were taken from the University of Western Ontario Dementia Study, a registry of dementia cases with clinical and psychometric follow up to necropsy based in a university memory disorders clinic with secondary and tertiary referrals. Data were available on 307 patients; 200 (65%) had clinically diagnosed Alzheimer's disease, 12 (4%) vascular dementia, 47 (15%) mixed dementia, and 48 (16%) had other diagnoses. One hundred and ninety two of 307 cases (63%) died and 122 of 192 fatalities (64%) had necropsies. The pathological material was interpreted in two ways, allowing and disallowing coexistent disease in making a diagnosis of Alzheimer's disease. In cases without necropsy, progressive cognitive loss was used as a marker for degenerative dementia. The outcome measures of interest were the positive predictive value of a clinical diagnosis of Alzheimer's disease allowing and disallowing coexistent diseases and with and without correction for cases that were not necropsied.
RESULTS
The clinical diagnoses differed significantly between the population who died and those who did not. In cases without necropsy, 22% had no dementia on follow up, concentrated in early cases and men, showing considerable scope for verification bias. The positive predictive value of a diagnosis of Alzheimer's disease was 81% including coexistent diseases, falling to 44% when limited to pure cases. Combined, these factors reduce the positive predictive value to 38% for pure Alzheimer's disease.
CONCLUSIONS
Correction for dual pathology and verification bias halves the positive predictive value of the clinical diagnosis of Alzheimer's disease. Data derived from necropsy studies cannot be extrapolated to the whole population. This has important implications including uncertainty about diagnosis and prognosis and a dilution effect in therapeutic trials in Alzheimer's disease.
目的
尸检确诊的阿尔茨海默病临床诊断准确率据称超过90%。这个数字存在两个谬误；它包括了阿尔茨海默病与其他影响认知的疾病并存的病例，而且报告这些数字的研究排除了未经尸检的病例（验证偏倚）。对这些误差的影响进行了评估。
方法
数据取自西安大略大学痴呆症研究，这是一个痴呆症病例登记处，在一所大学记忆障碍诊所进行临床和心理测量随访直至尸检，并接受二级和三级转诊。有307名患者的数据；200名（65%）临床诊断为阿尔茨海默病，12名（4%）为血管性痴呆，47名（15%）为混合性痴呆，48名（16%）有其他诊断。307例中有192例（63%）死亡，192例死亡病例中有122例（64%）进行了尸检。病理材料有两种解读方式，在诊断阿尔茨海默病时允许和不允许并存疾病。在未经尸检的病例中，进行性认知丧失被用作退行性痴呆的标志物。感兴趣的结果指标是阿尔茨海默病临床诊断的阳性预测值，允许和不允许并存疾病，以及对未经尸检的病例进行和不进行校正的情况。
结果
死亡人群和未死亡人群的临床诊断有显著差异。在未经尸检的病例中，22%在随访时无痴呆，集中在早期病例和男性中，显示出存在相当大的验证偏倚空间。阿尔茨海默病诊断的阳性预测值在包括并存疾病时为81%，仅限于单纯病例时降至44%。综合这些因素，单纯阿尔茨海默病的阳性预测值降至38%。
结论
对双重病理和验证偏倚进行校正后，阿尔茨海默病临床诊断的阳性预测值减半。来自尸检研究的数据不能外推至整个人群。这具有重要意义，包括诊断和预后的不确定性以及在阿尔茨海默病治疗试验中的稀释效应。
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