Alzheimer Neurobiology Centre,Geriatric Clinic, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Eur J Nucl Med Mol Imaging. 2013 Jan;40(1):104-14. doi: 10.1007/s00259-012-2237-2. Epub 2012 Sep 8.
Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies.
In this study 238 [(11)C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [(11)C]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 ± 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 ± 8 years) and 51 healthy controls (mean age 67.4 ± 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 ± 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype.
[(11)C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [(11)C]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [(11)C]PIB retention was observed in MCI ApoE ε4 carriers compared to non-ApoE ε4 carriers (p < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted.
This study demonstrated the robustness of [(11)C]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.
已经开发出淀粉样蛋白 PET 示踪剂，用于在体内检测阿尔茨海默病（AD）中的脑纤维状淀粉样蛋白沉积。为了成为 AD 的早期生物标志物，淀粉样蛋白 PET 示踪剂需要在多中心临床研究中进行分析。
本研究共汇集了来自五个欧洲中心的 238 个[(11)C]匹兹堡化合物-B（PIB）数据集。在这 238 个数据集中，排除了 18 个数据，留下了 97 名临床诊断为 AD（平均年龄 69±8 岁）、72 名轻度认知障碍（MCI；平均年龄 67.5±8 岁）和 51 名健康对照组（平均年龄 67.4±6 岁）的患者的[(11)C]PIB 数据集可用于分析。在 MCI 患者中，64 例患者进行了 28±15 个月的纵向随访。大多数参与者（220 名中的 175 名）还接受了载脂蛋白 E（ApoE）基因型检测。
AD 患者的大脑皮质和皮质下区域的[(11)C]PIB 保留明显高于年龄匹配的对照组。MCI 患者的[(11)C]PIB 保留处于中间水平，呈双峰分布（64%的 MCI PIB 阳性和 36%的 MCI PIB 阴性），与 AD 患者和对照组的模式明显不同。MCI ApoE ε4 携带者的[(11)C]PIB 保留明显高于非 ApoE ε4 携带者（p<0.005）。在 MCI PIB 阳性患者中，67%在随访时转化为 AD，而 MCI PIB 阴性患者无一例转化。
本研究在多中心环境下评估时，证明了[(11)C]PIB PET 作为脑内皮质纤维状淀粉样蛋白沉积标志物的稳健性。MCI PIB 阳性患者的记忆障碍比 MCI PIB 阴性患者更严重，预计每年以 25%的速度进展为 AD。没有 MCI PIB 阴性患者转化为 AD，因此 PIB 阴性对进展为 AD 的预测具有 100%的阴性预测值。这支持了 MCI 患者中 PIB 阳性扫描是前驱 AD 指标的观点。
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