Wagner Mark, Teichner Gordon, Bachman David L
Department of Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 9425-9691, USA.
Arch Clin Neuropsychol. 2003 Dec;18(8):893-903.
This report presents three cases of atypical degenerative dementias in order to illustrate challenges associated with the use of biologic markers of Alzheimer's disease (AD) for diagnosis and management. Clinical diagnostic methods followed the NINCDS-ADRDA criteria for AD. Additional diagnostic studies included serial neurocognitive testing, MRI, neuroSPECT, ApoE genotyping, and a CSF assay of tau and beta-amyloid(42). For patient 1, both the clinical and biologic markers were consistent with AD. The patient was diagnosed with AD with a high degree of confidence, even though the base rate of nonfamilial AD at this age group (<55 years) is exceedingly rare. This case argues favorably for the use of biologic markers to aid in confirming a diagnosis in an atypical dementia. Patient 2 met the NINCDS-ADRDA criteria for AD, although with less confidence. Neurocognitive data indicated a progressive right hemispheric syndrome, insight was preserved, and ApoE was 3/3, but tau concentrations and beta-amyloid(42) were highly consistent with cut-offs for AD; the differential fell on the Pick's disease/frontotemporal degeneration spectrum. Patient 3 had no clinical evidence of the disease, even when evaluated via extensive neurocognitive testing over a 2-year interval. However, ApoE was 4/4, and CSF assay of tau and beta-amyloid(42) were within the AD range. Therefore, while the CSF assay of tau and beta-amyloid(42) markers was confirmatory of AD, each case was highly atypical. Results illustrate the lack of normative data available when using biologic markers for highly atypical cases, calling into question their usefulness for such patients. These cases illustrate the interplay between neuropsychological and biological markers in establishing neurodegenerative diagnoses.
本报告介绍了三例非典型性退行性痴呆病例，以说明在使用阿尔茨海默病（AD）生物标志物进行诊断和管理时所面临的挑战。临床诊断方法遵循了AD的NINCDS-ADRDA标准。额外的诊断研究包括系列神经认知测试、MRI、神经SPECT、载脂蛋白E基因分型以及脑脊液中tau蛋白和β-淀粉样蛋白（42）检测。对于患者1，临床和生物标志物均与AD相符。尽管该年龄组（<55岁）非家族性AD的基础发病率极为罕见，但该患者仍被高度确信地诊断为AD。此病例有力地支持了使用生物标志物辅助诊断非典型性痴呆。患者2符合AD的NINCDS-ADRDA标准，但确定性较低。神经认知数据显示为进行性右半球综合征，自知力保留，载脂蛋白E为3/3，但tau蛋白浓度和β-淀粉样蛋白（42）与AD的临界值高度一致；鉴别诊断倾向于匹克病/额颞叶变性谱系。患者3即使在两年期间通过广泛的神经认知测试进行评估，也没有该疾病的临床证据。然而，载脂蛋白E为4/4，脑脊液中tau蛋白和β-淀粉样蛋白（42）检测结果在AD范围内。因此，虽然脑脊液中tau蛋白和β-淀粉样蛋白（42）标志物检测结果证实为AD，但每个病例都非常不典型。结果表明，在针对高度非典型病例使用生物标志物时缺乏规范性数据，这让人质疑其对此类患者的实用性。这些病例说明了神经心理学和生物学标志物在确立神经退行性疾病诊断中的相互作用。
