左侧大脑葡萄糖代谢在轻度认知障碍的淀粉样蛋白-β阳性者中下降。
Left lateralized cerebral glucose metabolism declines in amyloid-β positive persons with mild cognitive impairment.
机构信息
Department of Neurology, University of Leipzig, Germany.
Banner Alzheimer's Institute, Phoenix, AZ, USA; Neurogenomics Division, Translational Genomics Research Institute, University of Arizona, Arizona State University, Phoenix, AZ, USA; Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
出版信息
Neuroimage Clin. 2018 Jul 17;20:286-296. doi: 10.1016/j.nicl.2018.07.016. eCollection 2018.
BACKGROUND
Previous publications indicate that Alzheimer's Disease (AD) related cortical atrophy may develop in asymmetric patterns, with accentuation of the left hemisphere. Since fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the regional cerebral metabolic rate of glucose (rCMRgl) provide a sensitive and specific marker of neurodegenerative disease progression, we sought to investigate the longitudinal pattern of rCMRgl in amyloid-positive persons with mild cognitive impairment (MCI) and dementia, hypothesizing asymmetric declines of cerebral glucose metabolism.
METHODS
Using florbetapir PET and cerebrospinal fluid (CSF) measures to define amyloid-β (Aβ) positivity, 40 Aβ negative (Aβ-) cognitively unimpaired controls (CU; 76 ± 5y), 76 Aβ positive (Aβ+) persons with MCI (76 ± 7y) and 51 Aβ + persons with probable AD dementia (75 ± 7y) from the AD Neuroimaging Initiative (ADNI) were included in this study with baseline and 2-year follow-up FDG PET scans. The degree of lateralization of longitudinal rCMRgl declines in subjects with Aβ + MCI and AD in comparison with Aβ- CU were statistically quantified via bootstrapped lateralization indices [(LI); range - 1 (right) to 1 (left)].
RESULTS
Compared to Aβ- CU, Aβ + MCI patients showed marked left hemispheric lateralization (LI: 0.78). In contrast, modest right hemispheric lateralization (LI: -0.33) of rCMRgl declines was found in Aβ + persons with probable AD dementia. Additional comparisons of Aβ + groups (i.e. MCI and probable AD dementia) consequently indicated right hemispheric lateralization (LI: -0.79) of stronger rCMRgl declines in dementia stages of AD. For all comparisons, voxel-based analyses confirmed significant (pFWE<0.05) declines of rCMRgl within AD-typical brain regions. Analyses of cognitive data yielded predominant decline of memory functions in both MCI and dementia stages of AD.
CONCLUSIONS
These data indicate that in early stages, AD may be characterized by a more lateralized pattern of left hemispheric rCMRgl declines. However, metabolic differences between hemispheres appear to diminish with further progression of the disease.
背景
先前的研究表明，阿尔茨海默病（AD）相关的皮质萎缩可能呈不对称模式发展，左半球更为明显。由于氟代脱氧葡萄糖正电子发射断层扫描（FDG PET）测量脑葡萄糖代谢率（rCMRgl）提供了神经退行性疾病进展的敏感和特异性标志物，因此我们试图研究淀粉样蛋白阳性的轻度认知障碍（MCI）和痴呆患者的 rCMRgl 纵向模式，假设脑葡萄糖代谢呈不对称下降。
方法
使用氟代脱氧葡萄糖 PET 和脑脊液（CSF）测量来定义淀粉样蛋白-β（Aβ）阳性，共纳入 40 名 Aβ 阴性（Aβ-）认知正常对照组（CU；76±5 岁）、76 名 Aβ 阳性（Aβ+）MCI 患者（76±7 岁）和 51 名 Aβ+可能 AD 痴呆患者（75±7 岁），他们均来自 AD 神经影像学倡议（ADNI），基线和 2 年随访时均进行了 FDG PET 扫描。通过 bootstrap 侧化指数[（LI）；范围为-1（右）到 1（左）]对 Aβ+MCI 和 AD 患者的 rCMRgl 纵向下降程度进行统计学量化。
结果
与 Aβ-CU 相比，Aβ+MCI 患者表现出明显的左侧偏侧化（LI：0.78）。相反，在 Aβ+可能 AD 痴呆患者中，rCMRgl 下降的右偏侧化（LI：-0.33）则较小。对 Aβ+组（即 MCI 和可能 AD 痴呆）的进一步比较表明，在 AD 的痴呆阶段，rCMRgl 的下降具有更强的右偏侧化（LI：-0.79）。对于所有比较，基于体素的分析均证实了 AD 典型脑区 rCMRgl 的显著下降（pFWE<0.05）。认知数据分析表明，在 MCI 和 AD 痴呆阶段，记忆功能均呈主要下降。
结论
这些数据表明，在早期阶段，AD 可能以左半球 rCMRgl 下降更偏侧化的模式为特征。然而，随着疾病的进一步进展，半球之间的代谢差异似乎会减小。
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