Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults ≥ 55 Years Old. A Study Protocol for a Double-Blinded Randomized Controlled Clinical Trial.
Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults ≥ 55 Years Old. A Study Protocol for a Double-Blinded Randomized Controlled Clinical Trial.
复制标题
DOI：
10.14283/jpad.2022.3
复制
发表时间：
2022
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
酮体被认为是阿尔茨海默病(AD)大脑的一种“能量救援”，因为它没有充分利用葡萄糖。先前的研究表明，口服酮单酯(KME)可以安全地在人类中诱导强壮性酮症，并在AD的动物模型中显示出增强认知和减少病理的特性。然而，KME可以增强脑酮代谢、改善认知能力和参与AD致病级联反应的人类证据很少。目的探讨酮单酯(KME)对认知正常的老年代谢综合征患者的脑代谢、认知功能和AD发病的影响。双盲、随机、安慰剂对照临床试验。美国巴尔的摩国家老龄研究所临床分部。50名认知完好的成年人≥55岁，患有代谢综合征。含有25克KME或等卡路里安慰剂的饮料在28天内每天消费三次。初级：用磁共振波谱(MRS)测量楔前叶中的β-羟基丁酸酯(BHB)浓度。探索性：血浆和尿BHb，MRS检测多种脑和肌肉代谢物，PACC和NIH工具箱评估认知，AD的生物标志物和血浆细胞外小泡中的代谢介质，以及粪便微生物群。这是第一次研究AD生物标记物和KME对人类的认知影响。酮单酯是一种安全、耐受性好的药物，可引起强壮性酮症，动物实验表明它能改变AD的病理改变。通过在阿尔茨海默病高危人群中进行KME研究，我们希望弥合临床前证据与人类大脑代谢、促进认知和抗阿尔茨海默氏症效应之间的现有差距。
Ketone bodies have been proposed as an “energy rescue” for the Alzheimer’s disease (AD) brain, which underutilizes glucose. Prior research has shown that oral ketone monoester (KME) safely induces robust ketosis in humans and has demonstrated cognitive-enhancing and pathology-reducing properties in animal models of AD. However, human evidence that KME may enhance brain ketone metabolism, improve cognitive performance and engage AD pathogenic cascades is scarce. To investigate the effects of ketone monoester (KME) on brain metabolism, cognitive performance and AD pathogenic cascades in cognitively normal older adults with metabolic syndrome and therefore at higher risk for AD. Double-blinded randomized placebo-controlled clinical trial. Clinical Unit of the National Institute on Aging, Baltimore, US. Fifty cognitively intact adults ≥ 55 years old, with metabolic syndrome. Drinks containing 25 g of KME or isocaloric placebo consumed three times daily for 28 days. Primary: concentration of beta-hydroxybutyrate (BHB) in precuneus measured with Magnetic Resonance Spectroscopy (MRS). Exploratory: plasma and urine BHB, multiple brain and muscle metabolites detected with MRS, cognition assessed with the PACC and NIH toolbox, biomarkers of AD and metabolic mediators in plasma extracellular vesicles, and stool microbiome. This is the first study to investigate the AD-biomarker and cognitive effects of KME in humans. Ketone monoester is safe, tolerable, induces robust ketosis, and animal studies indicate that it can modify AD pathology. By conducting a study of KME in a population at risk for AD, we hope to bridge the existing gap between pre-clinical evidence and the potential for brain-metabolic, pro-cognitive, and anti-Alzheimer’s effects in humans.
登录
查看更多内容
影响因子：
29
作者：
Donohue, Michael C.;Sperling, Reisa A.;Salmon, David P.;Rentz, Dorene M.;Raman, Rema;Thomas, Ronald G.;Weiner, Michael;Aisen, Paul S.
通讯作者：
Aisen, Paul S.
影响因子：
3.1
作者：
Andreazza, Ana C.;Laksono, Isabelle;Baune, Bernhard T.
通讯作者：
Baune, Bernhard T.
影响因子：
9.9
作者：
Derby, Carol A.;Burns, Leah C.;Lipton, Richard B.
通讯作者：
Lipton, Richard B.
DOI：
10.1002/trc2.12050
发表时间：
2020-01-01
影响因子：
4.8
作者：
Cummings, Jeffrey;Lee, Garam;Zhong, Kate
通讯作者：
Zhong, Kate
影响因子：
5.3
作者：
Elamin M;Ruskin DN;Masino SA;Sacchetti P
通讯作者：
Sacchetti P