Tsuang D, Larson E B, Bowen J, McCormick W, Teri L, Nochlin D, Leverenz J B, Peskind E R, Lim A, Raskind M A, Thompson M L, Mirra S S, Gearing M, Schellenberg G D, Kukull W
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA.
Arch Neurol. 1999 Dec;56(12):1489-95. doi: 10.1001/archneur.56.12.1489.
A recent collaborative study found that apolipoprotein E (APOE) genotype, in conjunction with the clinical diagnosis of Alzheimer disease (AD), was useful in improving diagnostic specificity (correctly not diagnosing AD) relative to the clinical diagnosis alone. Since these samples are particularly enriched with patients with AD and the APOE epsilon4 allele, results may not be generalizable to patients seen in the general medical community.
To evaluate the diagnostic utility of the APOE genotype in diagnosing AD in a community-based case series from the largest health maintenance organization in an urban area.
We examined the effect of including APOE genotype on the diagnosis of AD in a community-based case series of patients presenting with memory complaints.
Clinical and neuropathologic diagnoses and APOE genotype were obtained from 132 patients who underwent evaluation for dementia and subsequent autopsy.
Sensitivity, specificity, and positive and negative predictive values given various combinations of clinical diagnoses and the presence of an APOE epsilon4 allele.
Of the 132 patients, 94 had neuropathologically confirmed AD, yielding a prevalence of 71%. The clinical diagnosis alone yielded a sensitivity of 84%, an estimated specificity of 50%, and positive and negative predictive values of 81% and 56%, respectively. The presence of an epsilon4 allele alone was associated with an estimated sensitivity of 59%, specificity of 71%, and positive and negative predictive values of 83% and 41%, respectively. Using the presence of clinical AD and an epsilon4 allele decreased the sensitivity to 49% and increased the specificity to 84%. The positive and negative predictive values were 88% and 40%, respectively. Alternatively, the clinical diagnosis of AD or the presence of an epsilon4 allele in individuals not meeting clinical criteria for AD increases the estimated sensitivity to 94% but decreases the specificity to 37%. The positive and negative predictive values were 79% and 70%, respectively. The changes in the sensitivity and specificity for the combined tests relative to clinical diagnosis alone offset each other. For lower prevalence communities, the positive predictive value will be much lower than those observed herein.
Our findings do not support the use of APOE genotyping alone in the diagnosis of AD in the general medical community. Although the presence of an epsilon4 allele in older persons with clinical AD increased the probability of having AD and the absence of an epsilon4 allele in this group decreased the probability of having AD, the association is not strong enough in the differential diagnosis of non-Alzheimer dementia and AD.
最近一项合作研究发现，载脂蛋白E（APOE）基因型与阿尔茨海默病（AD）的临床诊断相结合，相对于单纯的临床诊断，有助于提高诊断特异性（正确诊断非AD）。由于这些样本中AD患者和APOE ε4等位基因携带者特别富集，研究结果可能不适用于普通医疗群体中的患者。
在一个城市地区最大的健康维护组织的基于社区的病例系列中，评估APOE基因型在AD诊断中的效用。
我们在一个基于社区的有记忆障碍主诉患者的病例系列中，研究纳入APOE基因型对AD诊断的影响。
从132例接受痴呆评估及后续尸检的患者中获取临床和神经病理学诊断以及APOE基因型。
给出临床诊断与APOE ε4等位基因存在的各种组合下的敏感性、特异性、阳性预测值和阴性预测值。
132例患者中，94例经神经病理学确诊为AD，患病率为71%。仅临床诊断的敏感性为84%，估计特异性为50%，阳性预测值和阴性预测值分别为81%和56%。仅存在ε4等位基因时，估计敏感性为59%，特异性为71%，阳性预测值和阴性预测值分别为83%和41%。结合临床AD的存在和ε4等位基因会使敏感性降至49%，特异性提高到84%。阳性预测值和阴性预测值分别为88%和40%。或者，AD的临床诊断或不符合AD临床标准个体中ε4等位基因的存在会使估计敏感性提高到94%，但特异性降至37%。阳性预测值和阴性预测值分别为79%和70%。联合检测相对于单纯临床诊断的敏感性和特异性变化相互抵消。对于患病率较低的社区，阳性预测值将远低于本研究观察到的结果。
我们的研究结果不支持在普通医疗群体中单独使用APOE基因分型来诊断AD。虽然临床AD的老年人中存在ε4等位基因增加了患AD的可能性，而该群体中不存在ε4等位基因降低了患AD的可能性，但在非阿尔茨海默病性痴呆和AD的鉴别诊断中，这种关联不够强。
