淀粉样蛋白β对认知能力下降的影响受认知正常老年人神经完整性的调节。
The effect of amyloid β on cognitive decline is modulated by neural integrity in cognitively normal elderly.
机构信息
Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
出版信息
Alzheimers Dement. 2013 Nov;9(6):687-698.e1. doi: 10.1016/j.jalz.2012.10.012. Epub 2013 Mar 7.
OBJECTIVE
Alzheimer's disease (AD) pathology of amyloid β (Aβ) accumulation and neurodegeneration may be relevant to preclinical cognitive decline. The objective of this study was to relate AD-sensitive biomarkers of Aβ and neurodegeneration and their interaction to longitudinal cognitive change in cognitively normal elderly.
METHODS
Thirty-eight older people completed at least three consecutive neuropsychological examinations. Using positron emission tomography (PET), Aβ plaque burden was measured with [(11)C]Pittsburgh compound B (PiB). PiB retention was dichotomized into a positive (n = 13) and negative (n = 25) PiB status. Neurodegenerative biomarkers were extracted within AD-vulnerable regions of interest (ROIs)-namely, the hippocampus and temporoparietal cortical areas. Within each ROI, metabolism was quantified with [(18)F] fluorodeoxyglucose (FDG) PET, and the gray matter structure was evaluated using volume (hippocampus) or thickness (cortical regions). ROI-specific functional and structural biomarkers were combined further into cross-modality neurodegenerative composite measures. Using hierarchical regression models, PiB and the neurodegenerative biomarkers were related to cognitive trajectories.
RESULTS
PiB positivity was associated with memory and nonmemory worsening. The neurodegenerative biomarkers modified these relationships. Longitudinal cognitive decline was accelerated in those individuals who exhibited both PiB positivity and lower neurodegenerative biomarker scores, although the two measures appeared to be independent. PiB retention interacted predominantly with the cortical neurodegenerative composite for nonmemory change. Memory decline was best explained by the interaction between PiB and the hippocampal neurodegenerative composite, suggesting regional specificity of the neurodegenerative modulations.
CONCLUSIONS
Our findings indicate that cognitive trajectories deteriorate at a faster rate in cognitively normal individuals expressing Aβ burden and neurodegeneration within specific AD-sensitive regions.
目的
阿尔茨海默病（AD）的淀粉样蛋白β（Aβ）积累和神经退行性变病理学可能与临床前认知衰退有关。本研究的目的是将 AD 敏感的 Aβ和神经退行性变生物标志物及其相互作用与认知正常老年人的纵向认知变化相关联。
方法
38 名老年人至少完成了三次连续的神经心理学检查。使用正电子发射断层扫描（PET），用[11C]匹兹堡化合物 B（PiB）测量 Aβ斑块负担。PiB 保留分为阳性（n=13）和阴性（n=25）PiB 状态。在 AD 易损的感兴趣区域（ROI）内提取神经退行性生物标志物，即海马体和颞顶皮质区域。在每个 ROI 内，使用[18F]氟脱氧葡萄糖（FDG）PET 定量代谢，并用体积（海马体）或厚度（皮质区域）评估灰质结构。将 ROI 特异性功能和结构生物标志物进一步组合成跨模态神经退行性综合测量。使用分层回归模型，将 PiB 和神经退行性生物标志物与认知轨迹相关联。
结果
PiB 阳性与记忆和非记忆恶化相关。神经退行性生物标志物改变了这些关系。在表现出 PiB 阳性和较低神经退行性生物标志物评分的个体中，纵向认知下降加速，尽管这两个测量似乎是独立的。PiB 保留主要与皮质神经退行性复合指标的非记忆变化相互作用。记忆下降最好由 PiB 与海马神经退行性复合指标之间的相互作用来解释，表明神经退行性调节的区域特异性。
结论
我们的发现表明，在表达特定 AD 敏感区域内 Aβ负担和神经退行性变的认知正常个体中，认知轨迹以更快的速度恶化。
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