Jobst K A, Barnetson L P, Shepstone B J
OPTIMA, Radcliffe Infirmary Trust, Oxford, UK.
Int Psychogeriatr. 1998 Sep;10(3):271-302. doi: 10.1017/s1041610298005389.
In a prospective study of more than 200 cases of dementia and 119 controls, annual technetium-99m-hexamethyl-propylene amineoxime (99mTC-HMPAO) single-photon emission computed tomography (SPECT) and annual medial temporal lobe (MTL) oriented X-ray computed tomography (CT) have been used to evaluate the diagnostic potential of functional and structural neuroimaging in the differential diagnosis of dementia. Some subjects have had up to 7 annual evaluations. So far, of 151 who have died, 143 (95%) have come to necropsy. Histology is known for 118, of whom 80 had Alzheimer's disease (AD), 24 had other "non-AD" dementias, and 14 controls with no cognitive deficit in life also had no significant central nervous system pathology. To compare the findings in the dementias with the profile of structural and functional imaging in the cognitively normal elderly, scan data from 105 living, elderly controls without cognitive deficit have also been included in the analysis. All clinical diagnoses were according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) criteria, and all histopathological diagnoses according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. Early data from this cohort have suggested that the combination of both MTL atrophy seen on CT with parietotemporal hypoperfusion on SPECT may predict the pathology of AD. The diagnostic sensitivity, specificity, accuracy, and positive and negative predictive values of the NINCDS-ADRDA and DSM-III-R criteria could be assessed in this cohort against the gold standard of histopathology. The diagnostic potential of CT evidence of MTL atrophy alone, SPECT evidence of parietotemporal hypoperfusion alone, and the combination of both of these scan changes in the same individual could then be compared against the diagnostic accuracy of clinical operational criteria in the pathologically confirmed cases. Furthermore, all of these modalities could be compared with the diagnostic accuracy of apolipoprotein E4 (Apo E4) genotyping to predict AD in the histopathologically confirmed cohort. In this population, NINCDS "probable-AD" was 100% specific, 49% sensitive, and 66% accurate; "possible-AD" was only 61% specific, but 93% sensitive and 77% accurate; and the combination of both "probable-AD" and "possible-AD" was 61% specific, 96% sensitive, and 85% accurate. DSM-III-R criteria were 51% sensitive, 97% specific, and 66% accurate. In the same cases and including the 105 living, elderly controls, the diagnostic accuracy of the Oxford Project to Investigate Memory and Aging (OPTIMA) scanning criteria showed CT alone to be 85% sensitive, 78% specific, and 80% accurate; SPECT alone had 89% sensitivity, 80% specificity, and 83% accuracy; and the combination of the two was 80% sensitive, 93% specific, and 88% accurate. The Apo E4 genotype was 74% sensitive but yielded 40% false positives in the histologically confirmed series. The diagnostic accuracy afforded by this method of CT and SPECT used alone is better than that of any established clinical criteria and reveals that the combination of MTL atrophy and parietotemporal hypoperfusion is common in AD, much less common in other dementias, and rare in normal controls. In the NINCDS-ADRDA criteria "possible-AD" cases, the combination of CT and SPECT findings alone were better in all diagnostic indices than the presence of Apo E4 alone in predicting AD. The frequent occurrence of MTL atrophy in AD and also in other "non-AD" dementias later in the course of the disease suggests the concept of medial temporal lobe dementia. This could explain some of the overlap of clinical profiles in the dementias, particularly as the dementia progresses, making clinical differential diagnosis difficult. In this context, the use of SPECT can significantl
在一项对200多例痴呆患者和119名对照者的前瞻性研究中，每年使用锝-99m-六甲基丙烯胺肟（99mTC-HMPAO）单光子发射计算机断层扫描（SPECT）和每年进行内侧颞叶（MTL）定向X射线计算机断层扫描（CT），以评估功能和结构神经影像学在痴呆鉴别诊断中的诊断潜力。一些受试者接受了多达7次年度评估。到目前为止，在151名死亡者中，143人（95%）进行了尸检。已知118人的组织学情况，其中80人患有阿尔茨海默病（AD），24人患有其他“非AD”痴呆，14名生前无认知缺陷的对照者中枢神经系统也无明显病理改变。为了将痴呆患者的检查结果与认知正常老年人的结构和功能成像特征进行比较，分析中还纳入了105名无认知缺陷的在世老年对照者的扫描数据。所有临床诊断均依据美国国立神经疾病和中风研究所-阿尔茨海默病及相关疾病协会（NINCDS-ADRDA）和《精神疾病诊断与统计手册》（第3版，修订版；DSM-III-R）标准，所有组织病理学诊断依据阿尔茨海默病注册协会（CERAD）标准。该队列的早期数据表明，CT显示的MTL萎缩与SPECT显示的顶颞叶灌注不足相结合，可能预测AD的病理情况。在此队列中，可以对照组织病理学的金标准评估NINCDS-ADRDA和DSM-III-R标准的诊断敏感性、特异性、准确性以及阳性和阴性预测值。然后可以将单独的MTL萎缩的CT证据、单独的顶颞叶灌注不足的SPECT证据以及同一个体中这两种扫描变化的组合的诊断潜力，与病理确诊病例中临床操作标准的诊断准确性进行比较。此外，在组织病理学确诊的队列中，可以将所有这些方法与载脂蛋白E4（Apo E4）基因分型预测AD的诊断准确性进行比较。在这个人群中，NINCDS“可能的AD”特异性为100%，敏感性为49%，准确性为66%；“可能的AD”特异性仅为61%，但敏感性为93%，准确性为77%；“可能的AD”和“可能的AD”两者的组合特异性为61%，敏感性为96%，准确性为85%。DSM-III-R标准敏感性为51%，特异性为97%，准确性为66%。在相同病例中，包括105名在世的老年对照者，牛津记忆与衰老研究项目（OPTIMA）扫描标准的诊断准确性显示，单独CT敏感性为85%，特异性为78%，准确性为80%；单独SPECT敏感性为89%，特异性为80%，准确性为83%；两者结合敏感性为80%，特异性为93%，准确性为88%。在组织学确诊的系列中，Apo E4基因型敏感性为74%，但假阳性率为40%。单独使用这种CT和SPECT方法提供的诊断准确性优于任何既定的临床标准，并且表明MTL萎缩和顶颞叶灌注不足的组合在AD中常见，在其他痴呆中少见，在正常对照中罕见。在NINCDS-ADRDA标准的“可能的AD”病例中，单独的CT和SPECT检查结果组合在所有诊断指标上都比单独存在Apo E4在预测AD方面更好。AD以及其他“非AD”痴呆在病程后期频繁出现MTL萎缩，提示内侧颞叶痴呆的概念。这可以解释痴呆患者临床特征的一些重叠，特别是随着痴呆进展，使临床鉴别诊断变得困难。在这种情况下，使用SPECT可以显著地…… （原文最后单词拼写不完整）
