Cotta Ramusino Matteo, Massa Federico, Festari Cristina, Gandolfo Federica, Nicolosi Valentina, Orini Stefania, Nobili Flavio, Frisoni Giovanni B, Morbelli Silvia, Garibotto Valentina
Unit of Behavior Neurology and Dementia Research Center, IRCCS Mondino Foundation, via Mondino 2, 27100, Pavia, Italy.
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
Eur J Nucl Med Mol Imaging. 2024 Jun;51(7):1876-1890. doi: 10.1007/s00259-024-06631-y. Epub 2024 Feb 15.
Epidemiological and logistical reasons are slowing the clinical validation of the molecular imaging biomarkers in the initial stages of neurocognitive disorders. We provide an updated systematic review of the recent advances (2017-2022), highlighting methodological shortcomings.
Studies reporting the diagnostic accuracy values of the molecular imaging techniques (i.e., amyloid-, tau-, [18F]FDG-PETs, DaT-SPECT, and cardiac [123I]-MIBG scintigraphy) in predicting progression from mild cognitive impairment (MCI) to dementia were selected according to the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) method and evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Main eligibility criteria were as follows: (1) ≥ 50 subjects with MCI, (2) follow-up ≥ 3 years, (3) gold standard: progression to dementia or diagnosis on pathology, and (4) measures of prospective accuracy.
Sensitivity (SE) and specificity (SP) in predicting progression to dementia, mainly to Alzheimer's dementia were 43-100% and 63-94% for [F]FDG-PET and 64-94% and 48-93% for amyloid-PET. Longitudinal studies were lacking for less common disorders (Dementia with Lewy bodies-DLB and Frontotemporal lobe degeneration-FTLD) and for tau-PET, DaT-SPECT, and [123I]-MIBG scintigraphy. Therefore, the accuracy values from cross-sectional studies in a smaller sample of subjects (n > 20, also including mild dementia stage) were chosen as surrogate outcomes. DaT-SPECT showed 47-100% SE and 71-100% SP in differentiating Lewy body disease (LBD) from non-LBD conditions; tau-PET: 88% SE and 100% SP in differentiating DLB from Posterior Cortical Atrophy. [I]-MIBG scintigraphy differentiated LBD from non-LBD conditions with 47-100% SE and 71-100% SP.
Molecular imaging has a moderate-to-good accuracy in predicting the progression of MCI to Alzheimer's dementia. Longitudinal studies are sparse in non-AD conditions, requiring additional efforts in these settings.
流行病学和后勤方面的原因正在减缓神经认知障碍初始阶段分子影像生物标志物的临床验证进程。我们对近期进展（2017 - 2022年）进行了更新的系统评价，突出了方法学上的不足。
根据系统评价与Meta分析的首选报告项目（PRISMA）方法，选取报告分子影像技术（即淀粉样蛋白、tau蛋白、[18F]氟代脱氧葡萄糖正电子发射断层扫描（[18F]FDG - PET）、多巴胺转运体单光子发射计算机断层扫描（DaT - SPECT）和心脏[123I] - 间碘苄胍闪烁显像）在预测轻度认知障碍（MCI）进展为痴呆方面诊断准确性值的研究，并使用诊断准确性研究质量评估（QUADAS - 2）工具进行评估。主要纳入标准如下：（1）≥50例MCI受试者；（2）随访≥3年；（3）金标准：进展为痴呆或病理诊断；（4）前瞻性准确性测量。
在预测进展为痴呆（主要是阿尔茨海默病性痴呆）方面，[F]FDG - PET的敏感性（SE）和特异性（SP）分别为43% - 至100%和63% - 94%，淀粉样蛋白PET的SE和SP分别为64% - 94%和48% - 93%。对于不太常见的疾病（路易体痴呆 - DLB和额颞叶变性 - FTLD）以及tau - PET、DaT - SPECT和[123I] - MIBG闪烁显像，缺乏纵向研究。因此，选择在较小样本量受试者（n > 20，也包括轻度痴呆阶段）的横断面研究中的准确性值作为替代结果。DaT - SPECT在区分路易体病（LBD）与非LBD疾病方面显示出47% - 100%的SE和71% - 100%的SP；tau - PET：在区分DLB与后部皮质萎缩方面的SE为88%，SP为100%。[I] - MIBG闪烁显像在区分LBD与非LBD疾病方面的SE和SP为47% - 100%和71% - 100%。
分子影像在预测MCI进展为阿尔茨海默病性痴呆方面具有中等至良好的准确性。在非阿尔茨海默病（AD）情况下，纵向研究较少，在这些方面需要进一步努力。
