Hedderich Dennis M, Drost René, Goldhardt Oliver, Ortner Marion, Müller-Sarnowski Felix, Diehl-Schmid Janine, Zimmer Claus, Förstl Hans, Yakushev Igor, Jahn Thomas, Grimmer Timo
Department of Neuroradiology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
TUM-NIC Neuroimaging Center, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
Front Psychiatry. 2020 Aug 13;11:793. doi: 10.3389/fpsyt.2020.00793. eCollection 2020.
Recently, imaging biomarkers have gained importance for the characterization of patients with Alzheimer's disease; however, the relationship between regional biomarker expression and cognitive function remains unclear. In our study, we investigated associations between scores on CERAD neuropsychological assessment battery (CERAD-NAB) subtests with regional glucose metabolism, cortical thickness and amyloid deposition in patients with early Alzheimer's disease (AD) using [18F]-fluorodeoxyglucose (FDG), structural MRI, and 11C-Pittsburgh Compound B (PiB) positron emission tomography (PET), respectively. A total of 76 patients (mean age 68.4 ± 8.5 years, 57.9% male) with early AD (median global clinical dementia rating (CDR) score = 0.5, range: 0.5-2.0) were studied. Associations were investigated by correlation and multiple regression analyses. Scores on cognitive subtests were most closely predicted by regional glucose metabolism with explained variance up to a corrected R² of 0.518, followed by cortical thickness and amyloid deposition. Prediction of cognitive subtest performance was increased up to a corrected R² of 0.622 for Word List-Delayed Recall, when biomarker information from multiple regions and multiple modalities were included. For verbal, visuoconstructive and mnestic domains the closest associations with FDG-PET imaging were found in the left lateral temporal lobe, right parietal lobe, and posterior cingulate cortex, respectively. Decreased cortical thickness in parietal regions was most predictive of impaired subtest performance. Remarkably, cerebral amyloid deposition significantly predicted cognitive function in about half of the subtests but with smaller extent of variance explained (corrected R² ≤ 0.220). We conclude that brain metabolism and atrophy affect cognitive performance in a regionally distinct way. Significant predictions of cognitive function by PiB-PET in half of CERAD-NAB subtests suggest functional relevance even in symptomatic patients with AD, challenging the concept of plateauing cortical amyloid deposition early in the disease course. Our results underscore the complex spatial relationship between different imaging biomarkers.
最近，影像生物标志物在阿尔茨海默病患者的特征描述中变得愈发重要；然而，区域生物标志物表达与认知功能之间的关系仍不清楚。在我们的研究中，我们分别使用[18F]-氟脱氧葡萄糖（FDG）、结构磁共振成像（MRI）和11C-匹兹堡化合物B（PiB）正电子发射断层扫描（PET），调查了早期阿尔茨海默病（AD）患者在CERAD神经心理学评估量表（CERAD-NAB）子测试中的得分与区域葡萄糖代谢、皮质厚度和淀粉样蛋白沉积之间的关联。共研究了76例早期AD患者（平均年龄68.4±8.5岁，57.9%为男性）（全球临床痴呆评定量表（CDR）中位数得分=0.5，范围：0.5 - 2.0）。通过相关性分析和多元回归分析来研究这些关联。认知子测试的得分最能由区域葡萄糖代谢预测，解释方差高达校正后R²为0.518，其次是皮质厚度和淀粉样蛋白沉积。当纳入来自多个区域和多种模式的生物标志物信息时，单词列表延迟回忆的认知子测试表现预测的校正后R²提高到了0.622。对于语言、视觉构建和记忆领域，分别在左侧颞叶外侧、右侧顶叶和后扣带回皮质中发现了与FDG-PET成像最密切的关联。顶叶区域皮质厚度的降低最能预测子测试表现受损。值得注意的是，脑淀粉样蛋白沉积在大约一半的子测试中显著预测了认知功能，但解释的方差程度较小（校正后R²≤0.220）。我们得出结论，脑代谢和萎缩以区域特异性的方式影响认知表现。PiB-PET在CERAD-NAB一半的子测试中对认知功能有显著预测，这表明即使在有症状的AD患者中也具有功能相关性，这对疾病进程早期皮质淀粉样蛋白沉积达到平稳状态的概念提出了挑战。我们的结果强调了不同影像生物标志物之间复杂的空间关系。
