CHU Nantes, Centre de Mémoire et de Ressource et Recherche (CM2R), Nantes, France.
J Alzheimers Dis. 2012;28(2):323-36. doi: 10.3233/JAD-2011-110761.
The objective of this study was to examine the diagnostic accuracy of imaging and CSF biomarkers in clinically ambiguous dementia (CAD). 69 patients were prospectively followed. The endpoint was clinical diagnosis at follow-up of 24 months based upon existing criteria. Medial temporal lobe atrophy score on MRI, distinctive patterns on 99 mTc-HMPAO-SPECT, and CSF levels of amyloid-β peptide, total tau protein, and P-tau181P were used together with neuropsychological testing to assess Se (sensitivity) and Sp (specificity) of separate and combined markers. 60 patients reached the endpoint. A definite diagnosis was achieved in 48 patients. CSF biomarkers had a Sp of 71% and a Se of 100% for Alzheimer's disease (AD) diagnosis. Sp increased to 88% and 93% when MRI and MRI + SPECT were combined, at the expense of Se. CSF biomarkers levels also provided clues to frontotemporal (FTD) or vascular dementias (VaD) diagnosis when situated in an intermediate range between normal and pathological values. MRI and SPECT contributed mostly to the diagnosis of VaD (Se 88%, Sp 75%) and FTD (Se 73%, Sp 78%), respectively. Initial neuropsychological testing had a poor diagnostic accuracy, except for a neuropsychiatric inventory score >40 for the diagnosis of FTD (Se 73%, Sp 84%). Independent of the clinical diagnosis, medial temporal lobe atrophy and total-tau were best correlated with cognitive decline at 2 years. In conclusion, CSF biomarkers efficiently predict evolution toward an AD phenotype in CAD. Imaging biomarkers mostly contribute to the differential diagnosis between non-AD dementias. Initial neuropsychological testing was poorly contributive in CAD diagnosis.
本研究旨在探讨影像学和脑脊液生物标志物在临床不明确性痴呆（CAD）中的诊断准确性。69 例患者前瞻性随访。终点是 24 个月的临床诊断，根据现有标准进行随访。MRI 的内侧颞叶萎缩评分、99mTc-HMPAO-SPECT 的独特模式、以及脑脊液中淀粉样β肽、总tau 蛋白和 P-tau181P 的水平，与神经心理学测试一起用于评估单独和组合标志物的敏感性（Se）和特异性（Sp）。60 例患者达到终点。48 例患者获得明确诊断。CSF 标志物对阿尔茨海默病（AD）的诊断具有 71%的 Sp 和 100%的 Se。当 MRI 和 MRI+SPECT 联合使用时，Sp 增加到 88%和 93%，但 Se 降低。当 CSF 生物标志物水平处于正常和病理值之间的中间范围时，也为额颞叶（FTD）或血管性痴呆（VaD）的诊断提供线索。MRI 和 SPECT 分别对 VaD（Se 88%，Sp 75%）和 FTD（Se 73%，Sp 78%）的诊断贡献最大。初始神经心理学测试的诊断准确性较差，除了神经精神病学量表评分>40 用于 FTD 的诊断（Se 73%，Sp 84%）。无论临床诊断如何，内侧颞叶萎缩和总 tau 与 2 年内的认知下降相关性最好。总之，CSF 生物标志物能有效预测 CAD 向 AD 表型的进展。影像学生物标志物主要有助于非 AD 痴呆的鉴别诊断。初始神经心理学测试在 CAD 诊断中贡献较小。
