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评估衰老和阿尔茨海默病患者乳酸周转率的方法;LEAN 研究。

Methods to characterize lactate turnover in aging and Alzheimer's disease; The LEAN study.

机构信息

University of Kansas Alzheimer's Disease Research Center, United States of America; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States of America.

University of Kansas Alzheimer's Disease Research Center, United States of America; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States of America; Cell Biology and Physiology, Universtiy of Kansas Medical Center, Kansas City, KS, United States of America.

出版信息

Contemp Clin Trials. 2024 Nov;146:107682. doi: 10.1016/j.cct.2024.107682. Epub 2024 Sep 3.

Abstract

BACKGROUND

There is evidence that chronic exercise can benefit the brain, but the effects vary markedly between studies. One potential mechanism for exercise-related benefit is the increase in systemic lactate concentration that is well-characterized to occur during exercise. Lactate is known to cross the blood brain barrier and can be used readily as a fuel for neurons. This may be particularly important in Alzheimer's Disease, which is characterized by cerebral hypometabolism. However, little is known about how whole-body lactate metabolism differs between older adults and individuals with cognitive impairment. This information is critical when considering potential differences in responses to exercise in various cognitive diagnosis groups.

METHODS

Here we describe the use of a "lactate clamp" procedure to adjust blood lactate levels to approximate those achieved during exercise, but while at rest. This trial will compare lactate oxidation between cognitively healthy older adults and cognitively impaired participants. We will further evaluate the effect of acute lactate infusion on cognitive performance.

DISCUSSION

The findings of the study described here, the Lactate for Energy and Neurocognition trial (clinicaltrials.gov # NCT05207397) will add to our understanding of systemic lactate mechanics in cognitively healthy older adults and individuals with Alzheimer's Disease. These findings will be applicable to ongoing exercise trials and to future studies aimed at modulating systemic bioenergetic function in aging and Alzheimer's Disease.

摘要

背景

有证据表明,慢性运动有益于大脑,但不同研究之间的效果差异很大。运动相关益处的一个潜在机制是系统内乳酸浓度的增加,这在运动过程中得到了很好的描述。乳酸已知可以穿过血脑屏障,并可作为神经元的燃料。这在阿尔茨海默病中尤为重要,阿尔茨海默病的特征是大脑代谢不足。然而,关于老年人和认知障碍个体之间全身乳酸代谢的差异知之甚少。在考虑各种认知诊断组对运动反应的潜在差异时,这些信息至关重要。

方法

在这里,我们描述了使用“乳酸钳夹”程序来调整血液乳酸水平,使其近似于运动期间但在休息时达到的水平。这项试验将比较认知健康的老年人和认知受损参与者之间的乳酸氧化。我们将进一步评估急性乳酸输注对认知表现的影响。

讨论

这里描述的研究结果,即能量和神经认知的乳酸试验(clinicaltrials.gov # NCT05207397)将增加我们对认知健康的老年人和阿尔茨海默病患者中系统性乳酸力学的理解。这些发现将适用于正在进行的运动试验以及未来旨在调节衰老和阿尔茨海默病中系统性生物能量功能的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed86/11938302/e1ad557817fd/nihms-2063518-f0001.jpg

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Lactate as a fulcrum of metabolism.乳酸作为代谢的支点。
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