Sojkova Jitka, Beason-Held Lori, Zhou Yun, An Yang, Kraut Michael A, Ye Weigo, Ferrucci Luigi, Mathis Chester A, Klunk William E, Wong Dean F, Resnick Susan M
National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
J Nucl Med. 2008 Sep;49(9):1465-71. doi: 10.2967/jnumed.108.051946. Epub 2008 Aug 14.
Although cerebral amyloid deposition may precede cognitive impairment by decades, the relationship between amyloid deposition and longitudinal change in neuronal function has not, to our knowledge, been studied. The aim of this article was to determine whether individuals without dementia with high and low amyloid burden show different patterns of longitudinal regional cerebral blood flow (rCBF) changes in the years preceding measurement of amyloid deposition.
Twenty-eight participants without dementia (mean age+/-SD, 82.5+/-4.8 y; 6 mildly impaired) from the Baltimore Longitudinal Study of Aging underwent yearly resting-state (15)O-H(2)O PET scans for up to 8 y. (11)C-PIB images of amyloid deposition were acquired on average 10.8+/-0.8 y after the first CBF scan. (11)C-PIB distribution volume ratios of regions of interest were estimated by fitting a reference-tissue model to the measured time-activity curves. On the basis of mean cortical distribution volume ratios, participants were divided into groups with high or low (11)C-PIB retention. Differences in longitudinal rCBF changes between high- and low-(11)C-PIB groups were investigated by voxel-based analysis.
Longitudinal rCBF changes differed significantly between high- (n=10) and low- (n=18) (11)C-PIB groups (P <or= 0.001). Greater longitudinal decreases in rCBF in the high-(11)C-PIB group than in the low-(11)C-PIB group were seen in right anterior to middle cingulate, right supramarginal gyrus, left thalamus, and midbrain bilaterally. Greater increases in rCBF over time in the high-(11)C-PIB group were found in left medial and inferior frontal gyri, right precuneus, left inferior parietal lobule, and left postcentral gyrus.
In this group of older adults without dementia, those with high (11)C-PIB show greater longitudinal declines in rCBF in certain areas, representing regions with greater decrements in neuronal function. Greater longitudinal increases in rCBF are also observed in those with higher amyloid load and may represent an attempt to preserve neuronal function in these regions.
尽管脑淀粉样蛋白沉积可能在认知障碍出现前数十年就已发生,但据我们所知,淀粉样蛋白沉积与神经元功能纵向变化之间的关系尚未得到研究。本文的目的是确定在测量淀粉样蛋白沉积之前的几年里,淀粉样蛋白负荷高和低的无痴呆个体是否表现出不同的纵向局部脑血流量(rCBF)变化模式。
来自巴尔的摩衰老纵向研究的28名无痴呆参与者(平均年龄±标准差,82.5±4.8岁;6名轻度受损)接受了长达8年的每年一次静息状态(15)O-H2O PET扫描。淀粉样蛋白沉积的(11)C-PIB图像平均在第一次CBF扫描后10.8±0.8年采集。通过将参考组织模型拟合到测量的时间-活性曲线来估计感兴趣区域的(11)C-PIB分布体积比。根据平均皮质分布体积比,将参与者分为(11)C-PIB保留高或低的组。通过基于体素的分析研究高(11)C-PIB组和低(11)C-PIB组之间纵向rCBF变化的差异。
高(n = 10)和低(n = 18)(11)C-PIB组之间的纵向rCBF变化有显著差异(P≤0.001)。在右侧前扣带回至中扣带回、右侧缘上回、左侧丘脑以及双侧中脑,高(11)C-PIB组的rCBF纵向下降幅度大于低(11)C-PIB组。在高(11)C-PIB组中,随着时间的推移,左侧额内侧回和额下回、右侧楔前叶、左侧顶下小叶和左侧中央后回的rCBF增加幅度更大。
在这组无痴呆的老年人中,(11)C-PIB高的个体在某些区域的rCBF纵向下降幅度更大,这些区域代表神经元功能下降更大的区域。在淀粉样蛋白负荷较高的个体中也观察到rCBF纵向增加幅度更大,这可能代表这些区域试图维持神经元功能。