Larger temporal volume in elderly with high versus low beta-amyloid deposition
Larger temporal volume in elderly with high versus low beta-amyloid deposition
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DOI：
10.1093/brain/awq187
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发表时间：
2010-11-01
期刊：
影响因子：
14.5
通讯作者：
Rowe, Christopher C.
中科院分区：
文献类型：
--
作者：
Chetelat, Gael;Villemagne, Victor L.;Rowe, Christopher C.
β -淀粉样蛋白沉积是阿尔茨海默病的主要标志之一，被认为最终会导致神经元死亡。尸检和神经影像学研究一致报告了尽管高β -淀粉样蛋白负担但记录正常认知的病例。了解这些特殊受试者与没有-淀粉样蛋白沉积或同时有-淀粉样蛋白沉积和认知缺陷的受试者的区别是非常有趣的，即是什么使这些受试者能够抵抗病理病变的损害。[C-11]对健康对照、主观认知障碍、轻度认知障碍和阿尔茨海默病患者共149人进行了匹兹堡化合物B正电子发射断层扫描和磁共振脑扫描。比较高[C-11]匹斯堡化合物B与低[C-11]匹斯堡化合物B、高[C-11]匹斯堡化合物B与无认知缺陷的患者的磁共振数据。与低[C-11]匹兹堡化合物B的健康对照相比，颞叶（包括海马）灰质体积更大，与更好的情景记忆表现相关。使用不同的[C-11]匹兹堡化合物B阈值，校正[C-11]匹兹堡化合物B数据的部分平均，使用年龄，教育程度，小型精神状态检查，载脂蛋白E4和性别匹配的亚样本，并使用人工海马描绘代替基于体素的分析，获得了相同的结果。相比之下，在主观认知障碍的参与者中，与低[C-11]匹兹堡化合物B患者相比，在高[C-11]匹兹堡化合物B患者中发现了显著的灰质萎缩，与高[C-11]匹兹堡化合物B健康对照相比，主观认知障碍、轻度认知障碍和阿尔茨海默病的高[C-11]匹兹堡化合物B患者中也发现了显著的灰质萎缩。高[C-11]匹兹堡化合物B健康对照组的灰质体积较大，可能反映了组织对β -淀粉样蛋白的反应性反应，也可能反映了较高的“脑储备”和高[C-11]匹兹堡化合物B健康对照组中具有标准/低颞叶体积的受试者的代表性不足。我们的补充分析倾向于支持后一种假设。总的来说，我们的研究结果表明，β -淀粉样蛋白对认知的有害影响可能在脑（颞）容量较大的受试者中被延迟。
beta-Amyloid deposition is one of the main hallmarks of Alzheimer's disease thought to eventually cause neuronal death. Post-mortem and neuroimaging studies have consistently reported cases with documented normal cognition despite high beta-amyloid burden. It is of great interest to understand what differentiates these particular subjects from those without beta-amyloid deposition or with both beta-amyloid deposition and cognitive deficits, i.e. what allows these subjects to resist the damage of the pathological lesions. [C-11]Pittsburgh compound B positron emission tomography and magnetic resonance brain scans were obtained in 149 participants including healthy controls and patients with subjective cognitive impairment, mild cognitive impairment and Alzheimer's disease. Magnetic resonance data were compared between high versus low-[11C]Pittsburgh compound B cases, and between high-[C-11]Pittsburgh compound B cases with versus those without cognitive deficits. Larger temporal (including hippocampal) grey matter volume, associated with better episodic memory performance, was found in high- versus low-[C-11]Pittsburgh compound B healthy controls. The same finding was obtained using different [C-11]Pittsburgh compound B thresholds, correcting [C-11]Pittsburgh compound B data for partial averaging, using age, education, Mini-Mental State Examination, apolipoprotein E4 and sex-matched subsamples, and using manual hippocampal delineation instead of voxel-based analysis. By contrast, in participants with subjective cognitive impairment, significant grey matter atrophy was found in high-[C-11]Pittsburgh compound B cases compared to low-[C-11]Pittsburgh compound B cases, as well as in high-[C-11]Pittsburgh compound B cases with subjective cognitive impairment, mild cognitive impairment and Alzheimer's disease compared to high-[C-11]Pittsburgh compound B healthy controls. Larger grey matter volume in high-[C-11]Pittsburgh compound B healthy controls may reflect either a tissue reactive response to beta-amyloid or a combination of higher 'brain reserve' and under-representation of subjects with standard/low temporal volume in the high-[C-11]Pittsburgh compound B healthy controls. Our complementary analyses tend to support the latter hypotheses. Overall, our findings suggest that the deleterious effects of beta-amyloid on cognition may be delayed in those subjects with larger brain (temporal) volume.