1 Department of Nuclear Medicine, University Medical Centre, Freiburg, Germany 2 Centre of Geriatrics and Gerontology, University Medical Centre, Freiburg, Germany
2 Centre of Geriatrics and Gerontology, University Medical Centre, Freiburg, Germany 3 Department of Psychiatry and Psychotherapy, University Medical Centre, Freiburg, Germany.
Brain. 2015 Oct;138(Pt 10):3089-99. doi: 10.1093/brain/awv229. Epub 2015 Aug 13.
Clinical Alzheimer's disease affects both cerebral hemispheres to a similar degree in clinically typical cases. However, in atypical variants like logopenic progressive aphasia, neurodegeneration often presents asymmetrically. Yet, no in vivo imaging study has investigated whether lateralized neurodegeneration corresponds to lateralized amyloid-β burden. Therefore, using combined (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose positron emission tomography, we explored whether asymmetric amyloid-β deposition in Alzheimer's disease is associated with asymmetric hypometabolism and clinical symptoms. From our database of patients who underwent positron emission tomography with both (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose (n = 132), we included all amyloid-positive patients with prodromal or mild-to-moderate Alzheimer's disease (n = 69). The relationship between (11)C-Pittsburgh compound B binding potential and (18)F-fluorodeoxyglucose uptake was assessed in atlas-based regions of interest covering the entire cerebral cortex. Lateralizations of amyloid-β and hypometabolism were tested for associations with each other and with type and severity of cognitive symptoms. Positive correlations between asymmetries of Pittsburgh compound B binding potential and hypometabolism were detected in 6 of 25 regions (angular gyrus, middle frontal gyrus, middle occipital gyrus, superior parietal gyrus, inferior and middle temporal gyrus), i.e. hypometabolism was more pronounced on the side of greater amyloid-β deposition (range: r = 0.41 to 0.53, all P < 0.001). Stronger leftward asymmetry of amyloid-β deposition was associated with more severe language impairment (P < 0.05), and stronger rightward asymmetry with more severe visuospatial impairment (at trend level, P = 0.073). Similarly, patients with predominance of language deficits showed more left-lateralized amyloid-β burden and hypometabolism than patients with predominant visuospatial impairment and vice versa in several cortical regions. Associations between amyloid-β deposition and hypometabolism or cognitive impairment were predominantly observed in brain regions with high amyloid-β load. The relationship between asymmetries of amyloid-β deposition and hypometabolism in cortical regions with high amyloid-β load is in line with the detrimental effect of amyloid-β burden on neuronal function. Asymmetries were also concordant with lateralized cognitive symptoms, indicating their clinical relevance.
在临床上典型的病例中，临床阿尔茨海默病会同等程度地影响大脑两个半球。然而，在像失语法性进展性失语症这样的非典型变体中，神经退行性变通常呈不对称性。然而，尚无体内成像研究探讨偏侧性神经退行性变是否与偏侧性淀粉样β负担相对应。因此，我们使用联合 (11)C-匹兹堡复合物 B 和 (18)F-氟脱氧葡萄糖正电子发射断层扫描，研究了阿尔茨海默病中的不对称淀粉样β沉积是否与不对称性代谢低下和临床症状有关。从接受 (11)C-匹兹堡复合物 B 和 (18)F-氟脱氧葡萄糖正电子发射断层扫描的患者数据库中（n=132），我们纳入了所有淀粉样蛋白阳性的有前驱期或轻度至中度阿尔茨海默病的患者（n=69）。在涵盖整个大脑皮层的基于图谱的感兴趣区域中，评估了 (11)C-匹兹堡复合物 B 结合潜能与 (18)F-氟脱氧葡萄糖摄取之间的关系。测试了淀粉样蛋白-β和代谢低下的偏侧性之间的相互关系，以及与认知症状的类型和严重程度的关系。在 25 个区域中的 6 个区域（角回、额中回、中颞回、顶下小叶、下回和中回）中检测到了匹兹堡复合物 B 结合潜能和代谢低下之间的不对称性呈正相关（范围：r=0.41 至 0.53，所有 P<0.001）。左侧淀粉样蛋白-β沉积的不对称性越强，语言障碍越严重（P<0.05），右侧淀粉样蛋白-β沉积的不对称性越强，视觉空间障碍越严重（趋势水平，P=0.073）。同样，在几个皮质区域中，语言缺陷为主的患者比以视觉空间障碍为主的患者表现出更左偏的淀粉样蛋白-β负荷和代谢低下，反之亦然。在高淀粉样蛋白-β负荷的脑区，淀粉样蛋白-β沉积与代谢低下或认知障碍之间的相关性主要观察到。皮质区域中高淀粉样蛋白-β负荷的淀粉样蛋白-β沉积与代谢低下的不对称性与淀粉样蛋白负荷对神经元功能的有害影响一致。不对称性也与偏侧性认知症状一致，表明其具有临床意义。
