Coutinho Artur Martins, Busatto Geraldo F, de Gobbi Porto Fábio Henrique, de Paula Faria Daniele, Ono Carla Rachel, Garcez Alexandre Teles, Squarzoni Paula, de Souza Duran Fábio Luiz, de Oliveira Maira Okada, Tres Eduardo Sturzeneker, Brucki Sonia Maria Dozzi, Forlenza Orestes Vicente, Nitrini Ricardo, Buchpiguel Carlos Alberto
Laboratory of Nuclear Medicine (LIM 43), Department of Radiology and Oncology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Nucleo de Apoio a Pesquisa em Neurociência Aplicada (NAPNA), Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Eur J Nucl Med Mol Imaging. 2020 Oct;47(11):2666-2680. doi: 10.1007/s00259-020-04714-0. Epub 2020 Feb 13.
[F]FDG-PET and [C]PIB-PET are validated as neurodegeneration and amyloid biomarkers of Alzheimer's disease (AD). We used a PET staging system based on the 2018 NIA-AA research framework to compare the proportion of amyloid positivity (A+) and hypometabolism ((N)+) in cases of mild probable AD, amnestic mild cognitive impairment (aMCI), and healthy controls, incorporating an additional classification of abnormal [F]FDG-PET patterns and investigating the co-occurrence of such with A+, exploring [F]FDG-PET to generate hypotheses in cases presenting with clinical-biomarker "mismatches."
Elderly individuals (N = 108) clinically classified as controls (N = 27), aMCI (N = 43) or mild probable AD (N = 38) were included. Authors assessed their A(N) profiles and classified [F]FDG-PET neurodegenerative patterns as typical or non-typical of AD, performing re-assessments of images whenever clinical classification was in disagreement with the PET staging (clinical-biomarker "mismatches"). We also investigated associations between "mismatches" and sociodemographic and educational characteristics.
AD presented with higher rates of A+ and (N)+. There was also a higher proportion of A+ and (N)+ individuals in the aMCI group in comparison to controls, however without statistical significance regarding the A staging. There was a significant association between amyloid positivity and AD (N)+ hypometabolic patterns typical of AD. Non-AD (N)+ hypometabolism was seen in all A- (N)+ cases in the mild probable AD and control groups and [F]FDG-PET patterns classified such individuals as "SNAP" and one as probable frontotemporal lobar degeneration. All A- (N)- cases in the probable AD group had less than 4 years of formal education and lower socioeconomic status (SES).
The PET-based staging system unveiled significant A(N) differences between AD and the other groups, whereas aMCI and controls had different (N) staging, explaining the cognitive impairment in aMCI. [F]FDG-PET could be used beyond simple (N) staging, since it provided alternative hypotheses to cases with clinical-biomarker "mismatches." An AD hypometabolic pattern correlated with amyloid positivity. Low education and SES were related to dementia in the absence of biomarker changes.
[F]FDG-PET和[C]PIB-PET已被确认为阿尔茨海默病（AD）的神经退行性变和淀粉样蛋白生物标志物。我们使用了基于2018年美国国立衰老研究所-阿尔茨海默病协会（NIA-AA）研究框架的PET分期系统，比较轻度可能AD、遗忘型轻度认知障碍（aMCI）和健康对照者中淀粉样蛋白阳性（A+）和代谢减低（(N)+）的比例，纳入对异常[F]FDG-PET模式的额外分类，并研究其与A+的共现情况，探讨[F]FDG-PET在出现临床-生物标志物“不匹配”的病例中生成假设的作用。
纳入临床上分类为对照者（N = 27）、aMCI（N = 43）或轻度可能AD（N = 38）的老年人（N = 108）。作者评估了他们的A(N)特征，并将[F]FDG-PET神经退行性模式分类为AD典型或非典型，每当临床分类与PET分期不一致（临床-生物标志物“不匹配”）时对图像进行重新评估。我们还研究了“不匹配”与社会人口统计学和教育特征之间的关联。
AD患者的A+和(N)+发生率更高。与对照者相比，aMCI组中A+和(N)+个体的比例也更高，但在A分期方面无统计学意义。淀粉样蛋白阳性与AD典型的(N)+代谢减低模式之间存在显著关联。在轻度可能AD组和对照组的所有A-(N)+病例中均可见非AD (N)+代谢减低，[F]FDG-PET模式将这些个体分类为“快速进展性认知功能减退（SNAP）”，一例分类为可能的额颞叶痴呆。可能AD组中的所有A-(N)-病例接受正规教育的年限均少于4年且社会经济地位（SES）较低。
基于PET的分期系统揭示了AD与其他组之间显著的A(N)差异，而aMCI和对照者有不同的(N)分期，这解释了aMCI中的认知障碍。[F]FDG-PET可用于简单的(N)分期之外，因为它为临床-生物标志物“不匹配”的病例提供了替代假设。AD代谢减低模式与淀粉样蛋白阳性相关。低教育水平和SES与无生物标志物变化情况下的痴呆有关。
