A study of the clinical features of PIB-negative dementia patients in amyloid PET

背景/目的：我们之前发现，一些临床诊断为阿尔茨海默病（AD）的病例通过淀粉样蛋白成像被评为匹兹堡化合物b （PiB）阴性（即PiB阴性痴呆病例）。这些可能涉及脑内没有病理性淀粉样蛋白积累的疾病，如路易体痴呆（DLB）、额颞叶变性（FTLD）、嗜银颗粒病（AGD）、神经原纤维缠结为主的痴呆（NFTD）以及AD本身。本研究旨在通过脑脊液（CSF）分析和神经影像学检查详细分析pib阴性痴呆患者的临床特征。方法：64例临床诊断为AD的患者中，14例经pib正电子发射断层扫描（PET）判定为pib阴性。使用脑脊液生物标志物水平和磁共振成像（MRI）、氟脱氧葡萄糖(FDG)-PET、<123>^I-metaiodobenzylguanidine（MIBG）心肌闪烁成像和基于体素的形态测量（VBM）结果对其中11例进行进一步分析。结果：在<123>^I-MIBG心肌显像检查中，pib阴性痴呆组与健康对照组在早期和延迟期均有轻微差异，且H/M比pib阴性痴呆组明显高于DLB组。11例pib阴性痴呆患者脑脊液生物标志物及MRI、FDG-PET检查结果分析：AGD 3例，FTLD 3例，NFTD 1例，AD 2例。结论：pib阴性痴呆不太可能包括DLB，而最可能包括FTLD、AGD和NFTD等tau病。更好地了解pib阴性痴呆有望进一步提高阿尔茨海默病临床诊断的准确性。

Background/Aims : We previously found that some cases of clinically diagnosed Alzheimer's disease(AD) were rated as Pittsburgh compound-B(PiB)-negative by amyloid imaging(ie, cases of PiB-negative dementia). These may involve diseases that do not have pathological amyloid accumulation in the brain, such as dementia with Lewy bodies(DLB), frontotemporal lobar degeneration(FTLD), argyrophilic grain disease(AGD), and neurofibrillary tangle-predominant dementia(NFTD), as well as AD itself. The present study was designed to analyze the clinical features of PiB-negative dementia patients in detail with cerebrospinal fluid(CSF) analysis and neuroradiological tests. Methods : Of the 64 cases of clinically diagnosed AD, 14 were rated PiB-negative with PiB-positron emission tomography(PET). Eleven of these were further analyzed using CSF biomarker levels and findings from magnetic resonance imaging(MRI), fluorodeoxyglucose(FDG)-PET,<123>^I-metaiodobenzylguanidine(MIBG) myocardial scintigraphy, and voxel-based morphometry(VBM). Results : When examined by<123>^I-MIBG myocardial scintigraphy, the PiB-negative dementia group differed slightly from the healthy control group in both the early and delayed phases, and the H/M ratio was significantly higher in the PiB-negative dementia group than in the DLB group. Analyses of CSF biomarkers and MRI and FDG-PET findings among the 11 cases of PiB-negative dementia suggested AGD in 3 cases, FTLD in 3 cases, NFTD in 1 case, and AD in 2 cases. Conclusion : PiB-negative dementia is unlikely to include DLB, while it most likely includes diseases of tauopathy, such as FTLD, AGD, and NFTD. A better understanding of PiB-negative dementia is expected to further improve the accuracy of clinical diagnosis of AD.