Division of Neurology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada.
J Alzheimers Dis. 2024;101(s1):S443-S453. doi: 10.3233/JAD-240186.
Dementia represents one of the largest and most urgent public health problems across the globe. Modeling projections have estimated that delaying the onset of Alzheimer's disease (AD) by 6 months would reduce the prevalence by 5%, while a delay of 12 months would reduce the prevalence by 10%. One approach to achieving a delay in the onset of AD is to investigate lifestyle interventions that could be widely implemented with a favorable risk-benefit relationship and socioeconomic profile. Amongst such interventions, there is increasing evidence to support the use of ketogenic interventions in AD. Indeed, it is well known that cerebral glucose metabolism is impaired in AD, even at a preclinical stage, and a growing body of literature suggests that these findings may represent a primary pathogenic mechanism leading to neurodegeneration. Ketones are readily taken up by the brain and can serve as an alternative energy source for neurons and glia, hypothetically bypassing the glucose uptake deficit in AD. In this invited review we discuss the preclinical as well as clinical work aiming to increase ketones as a primary intervention in AD, including variations of the ketogenic diet, medium chain triglyceride supplementation, and newer, more experimental approaches.
痴呆症是全球最大且最紧迫的公共卫生问题之一。建模预测估计，将阿尔茨海默病（AD）的发病时间推迟 6 个月，患病率将降低 5%，而推迟 12 个月，患病率将降低 10%。实现 AD 发病延迟的一种方法是研究生活方式干预措施，这些措施可以通过有利的风险效益关系和社会经济状况得到广泛实施。在这些干预措施中，越来越多的证据支持在 AD 中使用生酮干预。事实上，众所周知，即使在临床前阶段，大脑葡萄糖代谢也受到损害，越来越多的文献表明，这些发现可能代表导致神经退行性变的主要致病机制。酮体很容易被大脑吸收，可以作为神经元和神经胶质的替代能源，假设可以绕过 AD 中的葡萄糖摄取缺陷。在这篇特邀评论中，我们讨论了旨在将酮体作为 AD 的主要干预措施的临床前和临床工作，包括生酮饮食的变化、中链甘油三酯的补充以及更新、更具实验性的方法。
