Center of Geriatrics and Gerontology Freiburg, University Hospital Freiburg, Freiburg, Germany.
J Nucl Med. 2013 Nov;54(11):1909-14. doi: 10.2967/jnumed.113.120378. Epub 2013 Oct 7.
Amyloid-β (Aβ) deposition is a pathologic hallmark of Alzheimer disease (AD). Although the typical spatial distribution pattern of Aβ deposition in early AD mainly involves regions distant from the hippocampus, the predominant clinical feature is impairment of hippocampus-dependent memory. We aimed at elucidating the relationship between neocortical Aβ load, regional neuronal function, and memory impairment.
Thirty patients with early AD underwent combined (11)C-Pittsburgh compound B ((11)C-PIB) and (18)F-FDG PET and memory assessments. Composite measures of hemispheric Aβ load were calculated by volume-weighted mean values of neocortical (11)C-PIB binding. Voxelwise (18)F-FDG uptake was used as a measure of regional glucose metabolism reflecting neuronal activity. We investigated the relationship between left- and right-hemispheric Aβ load and regional glucose metabolism (voxelwise analyses). In addition, we assessed the correlations of hemispheric Aβ load (region-of-interest-based analyses) and regional glucose metabolism (voxelwise analysis) with memory performance. Analyses were corrected for age and sex.
Higher Aβ load in the left hemisphere was associated with reduced glucose metabolism of the left medial temporal lobe (MTL; r(2) = 0.38) and correlated with worse wordlist recall (r = -0.37; partial correlation controlled for sex and age). Furthermore, wordlist recall correlated with regional glucose metabolism in the bilateral MTL and precuneus-posterior cingulate cortex and right lingual gyrus (r(2) = 0.24).
We demonstrated an association between the left-hemispheric Aβ load and impairment of the left MTL in AD at 2 different levels: regional hypometabolism and verbal memory. This correlation suggests that neocortical amyloid deposition is connected to or even drives neuronal dysfunction and neurodegeneration of the MTL, which is associated with impaired episodic memory processing as a clinical core symptom of AD.
淀粉样蛋白-β（Aβ）沉积是阿尔茨海默病（AD）的病理标志。尽管 AD 早期 Aβ沉积的典型空间分布模式主要涉及远离海马体的区域，但主要的临床特征是海马体依赖性记忆受损。我们旨在阐明新皮层 Aβ负荷、区域神经元功能和记忆障碍之间的关系。
30 例早期 AD 患者接受了（11）C-匹兹堡复合物 B（（11）C-PIB）和（18）F-FDG PET 以及记忆评估。通过计算新皮层（11）C-PIB 结合的体积加权平均值来计算半球 Aβ负荷的综合指标。体素水平的（18）F-FDG 摄取被用作反映神经元活动的区域葡萄糖代谢的指标。我们研究了左、右半球 Aβ负荷与区域葡萄糖代谢之间的关系（体素水平分析）。此外，我们评估了半球 Aβ负荷（基于感兴趣区的分析）和区域葡萄糖代谢（体素水平分析）与记忆表现的相关性。分析针对年龄和性别进行了校正。
左半球 Aβ负荷较高与左内侧颞叶（MTL；r(2) = 0.38）的葡萄糖代谢减少相关，并且与单词列表回忆（r = -0.37；部分相关，控制性别和年龄）相关。此外，单词列表回忆与双侧 MTL、楔前叶-后扣带回皮质和右侧舌回的区域葡萄糖代谢相关（r(2) = 0.24）。
我们在 2 个不同的水平上证明了 AD 中左半球 Aβ负荷与 MTL 损伤之间的关联：区域低代谢和言语记忆。这种相关性表明，新皮层淀粉样蛋白沉积与 MTL 的神经元功能障碍和神经退行性变相关，这与 AD 的临床核心症状即情景记忆处理受损有关。
