Effects of Brain Amyloid Deposition and Reduced Glucose Metabolism on the Default Mode of Brain Function in Normal Aging
Effects of Brain Amyloid Deposition and Reduced Glucose Metabolism on the Default Mode of Brain Function in Normal Aging
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DOI：
10.1523/jneurosci.2535-11.2011
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发表时间：
2011-08-03
影响因子：
5.3
通讯作者：
Ouchi, Yasuomi
中科院分区：
文献类型：
--
作者：
Kikuchi, Mitsuru;Hirosawa, Tetsu;Ouchi, Yasuomi
在正常衰老过程中脑β-淀粉样蛋白（A β）沉积被强调为阿尔茨海默病发展中的初始致病事件。许多最近的脑成像研究都集中在认知任务期间失活的区域[默认模式网络（DMN），即，内侧额回/前扣带皮层和楔前叶/后扣带皮层]，其中功能协调的强度或多或少受到大脑A β沉积的影响。在目前的正电子发射断层扫描研究中，为了研究在非痴呆老年人受试者（n = 22）中观察到的局部葡萄糖代谢改变和A β沉积是否在正常衰老期间DMN脑血流动力学协调变化中具有病理生理学重要性，我们用[F-18]FDG测量脑葡萄糖代谢，用[C-11]PIB测量A β沉积，和局部脑血流量在同一天的控制和工作记忆任务的H-2 O-15。使用感兴趣区域和统计参数映射对数据进行分析。我们的研究结果表明，A β沉积量与内侧额叶和内侧后区之间的血流动力学相似性呈负相关，并且较低的相似性与较差的工作记忆表现相关。与此相反，脑葡萄糖代谢与这种中间血流动力学相似性无关。这些发现表明，可追踪的A β沉积，而不是葡萄糖代谢低下，在大脑中起着重要作用，发生神经元失调的DMN沿着健康老年人的工作记忆差。
Brain beta-amyloid (A beta) deposition during normal aging is highlighted as an initial pathogenetic event in the development of Alzheimer's disease. Many recent brain imaging studies have focused on areas deactivated during cognitive tasks [the default mode network (DMN), i.e., medial frontal gyrus/anterior cingulate cortex and precuneus/posterior cingulate cortex], where the strength of functional coordination was more or less affected by cerebral A beta deposits. In the present positron emission tomography study, to investigate whether regional glucose metabolic alterations and A beta deposits seen in nondemented elderly human subjects (n = 22) are of pathophysiological importance in changes of brain hemodynamic coordination in DMN during normal aging, we measured cerebral glucose metabolism with [F-18]FDG, A beta deposits with [C-11]PIB, and regional cerebral blood flow during control and working memory tasks by H-2 O-15 on the same day. Data were analyzed using both region of interest and statistical parametric mapping. Our results indicated that the amount of A beta deposits was negatively correlated with hemodynamic similarity between medial frontal and medial posterior regions, and the lower similarity was associated with poorer working memory performance. In contrast, brain glucose metabolism was not related to this medial hemodynamic similarity. These findings suggest that traceable A beta deposition, but not glucose hypometabolism, in the brain plays an important role in occurrence of neuronal discoordination in DMN along with poor working memory in healthy elderly people.