Su L, Blamire A M, Watson R, He J, Hayes L, O'Brien J T
Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Institute of Cellular Medicine, Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, UK.
Transl Psychiatry. 2016 Aug 30;6(8):e877. doi: 10.1038/tp.2016.140.
Magnetic resonance spectroscopy has demonstrated metabolite changes in neurodegenerative disorders such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB); however, their pattern and relationship to clinical symptoms is unclear. To determine whether the spatial patterns of brain-metabolite changes in AD and DLB are regional or diffused, and to examine whether the key metabolite levels are associated with cognitive and non-cognitive symptoms, we acquired whole-brain spatially resolved 3T magnetic resonance spectroscopic imaging (MRSI) data from subjects with AD (N=36), DLB (N=35) and similarly aged controls (N=35). Voxel-wise measurement of N-acetylaspartate to creatine (NAA/Cr), choline to Cr (Cho/Cr), myo-inositol to Cr (mI/Cr) as well as glutamate and glutamine to Cr (Glx/Cr) ratios were determined using MRSI. Compared with controls, AD and DLB groups showed a significant decrease in most brain metabolites, with NAA/Cr, Cho/Cr and mI/Cr levels being reduced in posterior cingulate, thalamus, frontotemporal areas and basal ganglia. The Glx/Cr level was more widely decreased in DLB (posterior cingulate, hippocampus, temporal regions and caudate) than in AD (only in posterior cingulate). DLB was also associated with increased levels of Cho/Cr, NAA/Cr and mI/Cr in occipital regions. Changes in metabolism in the brain were correlated with cognitive and non-cognitive symptoms in the DLB but not in the AD group. The different patterns between AD and DLB may have implications for improving diagnosis, better understanding disease-specific neurobiology and targeting therapeutics. In addition, the study raised important questions about the role of occipital neuroinflammation and glial activation as well as the glutamatergic treatment in DLB.
磁共振波谱已证实神经退行性疾病（如阿尔茨海默病（AD）和路易体痴呆（DLB））中存在代谢物变化；然而，它们的模式以及与临床症状的关系尚不清楚。为了确定AD和DLB中脑代谢物变化的空间模式是区域性的还是弥漫性的，并检查关键代谢物水平是否与认知和非认知症状相关，我们从AD患者（N = 36）、DLB患者（N = 35）和年龄相仿的对照组（N = 35）中获取了全脑空间分辨3T磁共振波谱成像（MRSI）数据。使用MRSI确定了体素水平的N - 乙酰天门冬氨酸与肌酸（NAA/Cr）、胆碱与Cr（Cho/Cr）、肌醇与Cr（mI/Cr）以及谷氨酸和谷氨酰胺与Cr（Glx/Cr）的比值。与对照组相比，AD和DLB组的大多数脑代谢物显著减少，后扣带回、丘脑、额颞叶区域和基底神经节的NAA/Cr、Cho/Cr和mI/Cr水平降低。DLB组中Glx/Cr水平的降低范围（后扣带回、海马、颞叶区域和尾状核）比AD组（仅在后扣带回）更广泛。DLB还与枕叶区域Cho/Cr、NAA/Cr和mI/Cr水平升高有关。DLB组脑代谢变化与认知和非认知症状相关，而AD组则不然。AD和DLB之间的不同模式可能对改善诊断、更好地理解疾病特异性神经生物学以及靶向治疗具有重要意义。此外，该研究还提出了关于枕叶神经炎症和胶质细胞激活的作用以及DLB中谷氨酸能治疗的重要问题。
