Translational Neuroimaging Laboratory, Douglas Hospital, McGill University, Montreal, Quebec, Canada.
PLoS One. 2012;7(10):e47905. doi: 10.1371/journal.pone.0047905. Epub 2012 Oct 24.
The hypothetical model of dynamic biomarkers for Alzheimer's disease (AD) describes high amyloid deposition and hypometabolism at the mild cognitive impairment (MCI) stage. However, it remains unknown whether brain amyloidosis and hypometabolism follow the same trajectories in MCI individuals. We used the concept of early MCI (EMCI) and late MCI (LMCI) as defined by the Alzheimer's disease Neuroimaging Initiative (ADNI)-Go in order to compare the biomarker profile between EMCI and LMCI.
To examine the global and voxel-based neocortical amyloid burden and metabolism among individuals who are cognitively normal (CN), as well as those with EMCI, LMCI and mild AD.
In the present study, 354 participants, including CN (n = 109), EMCI (n = 157), LMCI (n = 39) and AD (n = 49), were enrolled between September 2009 and November 2011 through ADNI-GO and ADNI-2. Brain amyloid load and metabolism were estimated using [(18)F]AV45 and [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET, respectively. Uptake ratio images of [(18)F]AV45 and [(18)F]FDG were calculated by dividing the summed PET image by the median counts of the grey matter of the cerebellum and pons, respectively. Group differences of global [(18)F]AV45 and [(18)F]FDG were analyzed using ANOVA, while the voxel-based group differences were estimated using statistic parametric mapping (SPM).
EMCI patients showed higher global [(18)F]AV45 retention compared to CN and lower uptake compared to LMCI. SPM detected higher [(18)F]AV45 uptake in EMCI compared to CN in the precuneus, posterior cingulate, medial and dorsal lateral prefrontal cortices, bilaterally. EMCI showed lower [(18)F]AV45 retention than LMCI in the superior temporal, inferior parietal, as well as dorsal lateral prefrontal cortices, bilaterally. Regarding to the global [(18)F]FDG, EMCI patients showed no significant difference from CN and a higher uptake ratio compared to LMCI. At the voxel level, EMCI showed higher metabolism in precuneus, hippocampus, entorhinal and inferior parietal cortices, as compared to LMCI.
The present results indicate that brain metabolism remains normal despite the presence of significant amyloid accumulation in EMCI. These results suggest a role for anti-amyloid interventions in EMCI aiming to delay or halt the deposition of amyloid and related metabolism impairment.
阿尔茨海默病（AD）的动态生物标志物假设模型描述了轻度认知障碍（MCI）阶段的高淀粉样蛋白沉积和低代谢。然而，目前尚不清楚 MCI 个体中的脑淀粉样蛋白病和低代谢是否遵循相同的轨迹。我们使用阿尔茨海默病神经影像学倡议（ADNI）-GO 中定义的早期 MCI（EMCI）和晚期 MCI（LMCI）的概念来比较 EMCI 和 LMCI 之间的生物标志物特征。
检查认知正常（CN）个体以及 EMCI、LMCI 和轻度 AD 个体的全球和基于体素的新皮质淀粉样蛋白负担和代谢。
本研究共纳入 354 名参与者，包括 CN（n=109）、EMCI（n=157）、LMCI（n=39）和 AD（n=49），他们于 2009 年 9 月至 2011 年 11 月通过 ADNI-GO 和 ADNI-2 招募。分别使用[(18)F]AV45 和[(18)F]氟脱氧葡萄糖([(18)F]FDG) PET 估计脑淀粉样蛋白负荷和代谢。通过将总和 PET 图像除以小脑和桥脑灰质的中位数计数，计算[(18)F]AV45 和[(18)F]FDG 的摄取比图像。使用方差分析（ANOVA）分析[(18)F]AV45 和[(18)F]FDG 全局的组间差异，而基于体素的组间差异则使用统计参数映射（SPM）进行估计。
与 CN 相比，EMCI 患者表现出更高的全局[(18)F]AV45 保留，与 LMCI 相比，摄取更低。SPM 在楔前叶、后扣带回、内侧和背外侧前额叶皮质双侧检测到 EMCI 与 CN 相比更高的[(18)F]AV45 摄取。与 LMCI 相比，EMCI 在双侧颞上、顶下和背外侧前额叶皮质中表现出更低的[(18)F]AV45 保留。对于全局[(18)F]FDG，EMCI 患者与 CN 无显著差异，与 LMCI 相比摄取率更高。在体素水平上，与 LMCI 相比，EMCI 患者在楔前叶、海马体、内嗅皮质和顶下皮质中表现出更高的代谢。
本研究结果表明，尽管 EMCI 中存在明显的淀粉样蛋白沉积，但大脑代谢仍然正常。这些结果表明，针对淀粉样蛋白的干预措施在 EMCI 中的作用是延迟或阻止淀粉样蛋白的沉积和相关代谢损伤。
