Levin Fedor, Jelistratova Irina, Betthauser Tobey J, Okonkwo Ozioma, Johnson Sterling C, Teipel Stefan J, Grothe Michel J
German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Rostock, Germany.
Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
Alzheimers Res Ther. 2021 Oct 21;13(1):178. doi: 10.1186/s13195-021-00918-0.
We investigated regional amyloid staging characteristics in C-PiB-PET data from middle-aged to older participants at elevated risk for AD enrolled in the Wisconsin Registry for Alzheimer's Prevention.
We analyzed partial volume effect-corrected C-PiB-PET distribution volume ratio maps from 220 participants (mean age = 61.4 years, range 46.9-76.8 years). Regional amyloid positivity was established using region-specific thresholds. We used four stages from the frequency-based staging of amyloid positivity to characterize individual amyloid deposition. Longitudinal PET data was used to assess the temporal progression of stages and to evaluate the emergence of regional amyloid positivity in participants who were amyloid-negative at baseline. We also assessed the effect of amyloid stage on longitudinal cognitive trajectories.
The staging model suggested progressive accumulation of amyloid from associative to primary neocortex and gradually involving subcortical regions. Longitudinal PET measurements supported the cross-sectionally estimated amyloid progression. In mixed-effects longitudinal analysis of cognitive follow-up data obtained over an average period of 6.5 years following the baseline PET measurement, amyloid stage II showed a faster decline in executive function, and advanced amyloid stages (III and IV) showed a faster decline across multiple cognitive domains compared to stage 0.
Overall, the C-PiB-PET-based staging model was generally consistent with previously derived models from F-labeled amyloid PET scans and a longitudinal course of amyloid accumulation. Differences in longitudinal cognitive decline support the potential clinical utility of in vivo amyloid staging for risk stratification of the preclinical phase of AD even in middle-aged to older individuals at risk for AD.
我们在威斯康星州阿尔茨海默病预防登记处登记的患阿尔茨海默病风险升高的中年至老年参与者的C-PiB-PET数据中，研究了区域淀粉样蛋白分期特征。
我们分析了220名参与者（平均年龄=61.4岁，范围46.9 - 76.8岁）的经部分容积效应校正的C-PiB-PET分布容积比图。使用区域特异性阈值确定区域淀粉样蛋白阳性。我们采用基于频率的淀粉样蛋白阳性分期的四个阶段来描述个体淀粉样蛋白沉积情况。纵向PET数据用于评估阶段的时间进展，并评估基线时淀粉样蛋白阴性的参与者中区域淀粉样蛋白阳性的出现情况。我们还评估了淀粉样蛋白阶段对纵向认知轨迹的影响。
分期模型表明淀粉样蛋白从联合皮质向初级新皮质逐渐积累，并逐渐累及皮质下区域。纵向PET测量结果支持了横断面估计的淀粉样蛋白进展情况。在基线PET测量后平均6.5年期间获得的认知随访数据的混合效应纵向分析中，淀粉样蛋白II期显示执行功能下降更快，与0期相比，晚期淀粉样蛋白阶段（III期和IV期）在多个认知领域下降更快。
总体而言，基于C-PiB-PET的分期模型与先前从F标记淀粉样蛋白PET扫描得出的模型以及淀粉样蛋白积累的纵向过程基本一致。纵向认知下降的差异支持了体内淀粉样蛋白分期在阿尔茨海默病临床前期风险分层中的潜在临床应用价值，即使对于有患阿尔茨海默病风险的中年至老年个体也是如此。
