Basal cerebral metabolism may modulate the cognitive effects of Abeta in mild cognitive impairment: an example of brain reserve.
Basal cerebral metabolism may modulate the cognitive effects of Abeta in mild cognitive impairment: an example of brain reserve.
复制标题
基础大脑代谢可能会调节Abeta在轻度认知障碍中的认知作用：大脑储备的一个例子。
DOI：
10.1523/jneurosci.3669-09.2009
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发表时间：
2009-11-25
期刊：
影响因子：
--
通讯作者：
Klunk WE
中科院分区：
文献类型：
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作者：
Cohen AD;Price JC;Weissfeld LA;James J;Rosario BL;Bi W;Nebes RD;Saxton JA;Snitz BE;Aizenstein HA;Wolk DA;Dekosky ST;Mathis CA;Klunk WE
在阿尔茨海默病（AD）患者中，通过匹兹堡化合物-B（PiB）正电子发射断层扫描（PET）测量的β淀粉样蛋白（Aβ）负荷与使用[18 F]氟-2-脱氧-D-葡萄糖（FDG）的脑代谢之间的负相关性表明局部Aβ诱导的代谢损伤。然而，这种关系尚未在轻度认知障碍（MCI）或淀粉样蛋白阳性对照中得到很好的研究。在此，我们通过对淀粉样蛋白阳性对照受试者和MCI或AD患者进行基于感兴趣区域和基于体素的分析，探讨了Aβ沉积与代谢的相关性。AD患者顶叶和楔前叶皮质的代谢与PiB的局部滞留呈负相关，与额叶皮质的PiB滞留呈较远的负相关。在淀粉样蛋白阳性对照中，未观察到相关性的明确模式。在MCI患者中，基本上没有显著的负相关，但代谢和PiB保留之间经常存在显著的正相关。MCI组扣带回前部代谢与多数脑区的PiB呈正相关，楔前叶/顶叶皮质代谢与PiB的存留呈局部正相关。然而，与年龄匹配的对照组相比，MCI患者的代谢并未显着增加，这排除了Aβ沉积直接导致反应性高代谢的可能性。这表明，在MCI中，较高的基础代谢可能会加剧Aβ沉积或增加足以用于AD临床诊断的认知障碍所需的Aβ水平。只有在广泛的Aβ沉积存在较长时间后，Aβ才成为临床AD代谢降低的驱动力，并且仅在更脆弱的大脑区域，如顶叶和楔前叶皮质。
Inverse correlations between amyloid-β (Aβ) load measured by Pittsburgh Compound-B (PiB) positron emission tomography (PET) and cerebral metabolism using [18F]fluoro-2-deoxy-D-glucose (FDG) in Alzheimer’s disease (AD) patients, suggest local Aβ-induced metabolic insults. However, this relationship has not been well studied in mild cognitive impairment (MCI) or amyloid-positive controls. Here, we explored associations of Aβ deposition with metabolism via both region-of-interest-based and voxel-based analyses in amyloid-positive control subjects and patients with MCI or AD. Metabolism in parietal and precuneus cortices of AD patients was negatively correlated with PiB retention locally, and more distantly with PiB retention in frontal cortex. In amyloid-positive controls, no clear patterns in correlations were observed. In MCI patients, there were essentially no significant, negative correlations, but there were frequent significant positive correlations between metabolism and PiB retention. Metabolism in anterior cingulate showed positive correlations with PiB in most brain areas in MCI, and metabolism and PiB retention were positively correlated locally in precuneus/parietal cortex. However, there was no significant increase in metabolism in MCI compared to age-matched controls, negating the possibility that Aβ deposition directly caused reactive hypermetabolism. This suggests that, in MCI, higher basal metabolism could either be exacerbating Aβ deposition or increasing the level of Aβ necessary for cognitive impairment sufficient for the clinical diagnosis of AD. Only after extensive Aβ deposition has been present for longer periods of time does Aβ become the driving force for decreased metabolism in clinical AD and, only in more vulnerable brain regions such as parietal and precuneus cortices.