Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Adv Nutr. 2020 Nov 16;11(6):1583-1602. doi: 10.1093/advances/nmaa073.
Alzheimer disease (AD) is a global health concern with the majority of pharmacotherapy choices consisting of symptomatic treatment. Recently, ketogenic therapies have been tested in randomized controlled trials (RCTs), focusing on delaying disease progression and ameliorating cognitive function. The present systematic review aimed to aggregate the results of trials examining the effects of ketogenic therapy on patients with AD/mild cognitive impairment (MCI). A systematic search was conducted on PubMed, CENTRAL, clinicaltrials.gov, and gray literature for RCTs performed on adults, published in English until 1 April, 2019, assessing the effects of ketogenic therapy on MCI and/or AD compared against placebo, usual diet, or meals lacking ketogenic agents. Two researchers independently extracted data and assessed risk of bias with the Cochrane tool. A total of 10 RCTs were identified, fulfilling the inclusion criteria. Interventions were heterogeneous, acute or long term (45-180 d), including adherence to a ketogenic diet, intake of ready-to-consume drinks, medium-chain triglyceride (MCT) powder for drinks preparation, yoghurt enriched with MCTs, MCT capsules, and ketogenic formulas/meals. The use of ketoneurotherapeutics proved effective in improving general cognition using the Alzheimer's Disease Assessment Scale-Cognitive, in interventions of either duration. In addition, long-term ketogenic therapy improved episodic and secondary memory. Psychological health, executive ability, and attention were not improved. Increases in blood ketone concentrations were unanimous and correlated to the neurocognitive battery based on various tests. Cerebral ketone uptake and utilization were improved, as indicated by the global brain cerebral metabolic rate for ketones and [11C] acetoacetate. Ketone concentrations and cognitive performance differed between APOE ε4(+) and APOE ε4(-) participants, indicating a delayed response among the former and an improved response among the latter. Although research on the subject is still in the early stages and highly heterogeneous in terms of study design, interventions, and outcome measures, ketogenic therapy appears promising in improving both acute and long-term cognition among patients with AD/MCI. This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019128311.
阿尔茨海默病（AD）是一个全球性的健康问题，大多数药物治疗选择都集中在症状治疗上。最近，生酮疗法已经在随机对照试验（RCT）中进行了测试，重点是延缓疾病进展和改善认知功能。本系统评价旨在汇总评估生酮疗法对 AD/轻度认知障碍（MCI）患者影响的试验结果。在 PubMed、CENTRAL、clinicaltrials.gov 和灰色文献中，对成人进行了系统搜索，这些试验发表于 2019 年 4 月 1 日前的英文文献，评估了生酮疗法与安慰剂、常规饮食或不含生酮剂的膳食相比，对 MCI 和/或 AD 的影响。两名研究人员独立提取数据，并使用 Cochrane 工具评估偏倚风险。确定了 10 项符合纳入标准的 RCT。干预措施具有异质性，为急性或长期（45-180 天），包括遵循生酮饮食、饮用准备好的饮料、用于饮料制备的中链甘油三酯（MCT）粉、富含 MCT 的酸奶、MCT 胶囊以及生酮配方/膳食。使用酮神经治疗剂在改善认知方面是有效的，使用阿尔茨海默病评估量表-认知评估，在任何一种持续时间的干预措施中。此外，长期生酮治疗改善了情景和次要记忆。心理健康、执行能力和注意力没有得到改善。血液酮浓度的增加是一致的，并与基于各种测试的神经认知电池相关。大脑酮摄取和利用得到改善，如全球脑酮代谢率和[11C]乙酰乙酸所示。酮浓度和认知表现因 APOE ε4（+）和 APOE ε4（-）参与者而异，表明前者反应延迟，后者反应改善。尽管该主题的研究仍处于早期阶段，并且在研究设计、干预措施和结果测量方面高度异质，但生酮疗法似乎有希望改善 AD/MCI 患者的急性和长期认知。本系统评价在 www.crd.york.ac.uk/prospero 上注册为 CRD42019128311。
