A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer's disease
A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer's disease
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DOI：
10.1016/j.exger.2017.07.004
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发表时间：
2018-07-01
影响因子：
3.9
通讯作者：
Cunnane, S. C.
中科院分区：
文献类型：
--
作者：
Croteau, E.;Castellano, C. A.;Cunnane, S. C.
简介：脑葡萄糖代谢的恶化先于阿尔茨海默病（AD）的临床发作，似乎有助于其病因。酮体，主要是β-羟基丁酸和乙酰乙酸，是葡萄糖的主要替代脑燃料。有报道认为AD患者脑内酮代谢无明显改变，但MCI患者脑内酮代谢无明显改变，目的：比较MCI患者脑内酮代谢的变化（葡萄糖和乙酰乙酸）和认知健康老年人对照（CTL）、轻度认知障碍（MCI）和早期AD的一些大脑形态学特征。方法：年龄和代谢表型相似的24例CTL、20例MCI和19例AD进行了双示踪剂PET和MRI方案。采用葡萄糖类似物[F-18]-FDG和酮PET示踪剂[C-11]-AcAc，测定葡萄糖（K-Glu，CMRGlu）和乙酰乙酸（K-AcAc，CMRAcAc）的摄取速率常数和脑代谢率。结果：AD患者额、顶、颞叶及扣带回CMRGlu值较对照组低11%（p < 0.05）;在这些相同区域和皮质下区域，K-Glu降低了15%。与CTL相比，在MCI中，扣带回中存在类似于7%的葡萄糖代谢低下。CTL与MCI或AD之间的区域或全脑CMRAcAc或KAcAc均无显著差异。与CTL相比，AD患者的灰质体积减少和皮质变薄更为普遍，而MCI患者的灰质体积仅在颞叶皮质减少，皮质变薄在颞叶和扣带区最为明显。讨论：脑葡萄糖和乙酰乙酸代谢的定量动力学PET和MRI成像方案证实，MCI和AD患者的脑经历结构性萎缩和脑能量代谢降低并证明大脑能量代谢的恶化是葡萄糖特有的。这些结果表明，生酮干预增加大脑的能量可用性是必要的，试图通过补偿MCI和AD中的大脑葡萄糖不足来延迟进一步的认知下降。(C)2017爱思唯尔公司All rights reserved.
Introduction: Deteriorating brain glucose metabolism precedes the clinical onset of Alzheimer's disease (AD) and appears to contribute to its etiology. Ketone bodies, mainly beta-hydroxybutyrate and acetoacetate, are the primary alternative brain fuel to glucose. Some reports suggest that brain ketone metabolism is unchanged in AD but, to our knowledge, no such data are available for MCI.Objective: To compare brain energy metabolism (glucose and acetoacetate) and some brain morphological characteristics in cognitively healthy older adult controls (CTL), mild cognitive impairment (MCI) and early AD.Methods: 24 CTL, 20 MCI and 19 AD of similar age and metabolic phenotype underwent a dual-tracer PET and MRI protocol. The uptake rate constants and cerebral metabolic rate of glucose (K-Glu, CMRGlu) and acetoacetate (K-AcAc, CMRAcAc) were evaluated with PET using [F-18]-fluorodeoxyglucose ([F-18]-FDG), a glucose analogue, and [C-11]acetoacetate ([C-11]-AcAc), a ketone PET tracer. Regional brain volume and cortical thickness were evaluated by T1-weighted MRI.Results: In AD compared to CTL, CMRGlu was similar to 11% lower in the frontal, parietal, temporal lobes and in the cingulate gyrus (p < 0.05). K-Glu was similar to 15% lower in these same regions and also in subcortical regions. In MCI compared to CTL, similar to 7% glucose hypometabolism was present in the cingulate gyrus. Neither regional nor whole brain CMRAcAc or KAcAc were significantly different between CTL and MCI or AD. Reduced gray matter volume and cortical thinning were widespread in AD compared to CTL, whereas, in MCI compared to CTL, volumes were reduced only in the temporal cortex and cortical thinning was most apparent in temporal and cingulate regions.Discussion: This quantitative kinetic PET and MRI imaging protocol for brain glucose and acetoacetate metabolism confirms that the brain undergoes structural atrophy and lower brain energy metabolism in MCI and AD and demonstrates that the deterioration in brain energy metabolism is specific to glucose. These results suggest that a ketogenic intervention to increase energy availability for the brain is warranted in an attempt to delay further cognitive decline by compensating for the brain glucose deficit in MCI and AD. (C) 2017 Elsevier Inc. All rights reserved.