Ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease: A systematic review and critical appraisal.
Ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease: A systematic review and critical appraisal.
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DOI：
10.3389/fneur.2023.1123290
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发表时间：
2023
影响因子：
3.4
通讯作者：
Bohnen, Nicolaas I.
中科院分区：
文献类型：
--
作者：
Bohnen, Jeffrey L. B.;Albin, Roger L.;Bohnen, Nicolaas I.
在2005年发表的帕金森病概念验证研究之后，对治疗酮症作为神经退行性疾病的潜在疗法-特别是轻度认知障碍（MCI）、阿尔茨海默病（AD）和帕金森病（PD）-的兴趣越来越大。为了对新出现的临床证据进行客观评估，并为未来的研究提供有针对性的建议，我们回顾了自2005年以来报道的涉及轻度认知障碍，阿尔茨海默病和帕金森病的生酮干预的临床试验。使用美国神经病学学会治疗试验评级标准对临床证据水平进行系统性审查。确定了10项AD、3项MCI和5项PD治疗生酮试验。采用美国神经病学学会治疗试验分级标准对临床证据的各个等级进行客观评估。我们发现轻度认知障碍受试者和载脂蛋白ε4等位基因（APOε4-）阴性的轻度至中度阿尔茨海默病受试者的认知改善的“B”类证据（可能有效）。我们发现了载脂蛋白ε4等位基因（APOε4+）阳性的轻度至中度阿尔茨海默病患者认知稳定的U级证据（未经证实）。我们发现帕金森病患者非运动功能改善的“C”类证据（可能有效）和运动功能改善的“U”类证据（未经证实）。帕金森病的试验数量非常少，最好的证据表明急性补充剂有望提高运动耐力。迄今为止文献的局限性包括文献中目前评估的生酮干预的范围（即，主要是饮食或中链甘油三酯干预），使用更有效制剂的研究较少（例如，外源性酮酯）。总的来说，迄今为止最有力的证据表明，轻度认知障碍患者和载脂蛋白ε4等位基因阴性的轻度至中度阿尔茨海默病患者的认知改善。在这些人群中进行更大规模的关键性试验是合理的。需要进一步研究以优化生酮干预在不同临床背景下的利用，并更好地描述载脂蛋白ε4等位基因阳性患者对治疗性酮症的反应，因为可能需要改良干预。
There is increasing interest in therapeutic ketosis as a potential therapy for neurodegenerative disorders–in particular, mild cognitive impairment (MCI), Alzheimer's disease (AD), and Parkinson's disease (PD)–following a proof-of-concept study in Parkinson's disease published in 2005. To provide an objective assessment of emerging clinical evidence and targeted recommendations for future research, we reviewed clinical trials involving ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease reported since 2005. Levels of clinical evidence were systematically reviewed using the American Academy of Neurology criteria for rating therapeutic trials. 10 AD, 3 MCI, and 5 PD therapeutic ketogenic trials were identified. Respective grades of clinical evidence were objectively assessed using the American Academy of Neurology criteria for rating therapeutic trials. We found class “B” evidence (probably effective) for cognitive improvement in subjects with mild cognitive impairment and subjects with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele (APOε4-). We found class “U” evidence (unproven) for cognitive stabilization in individuals with mild-to-moderate Alzheimer's disease positive for the apolipoprotein ε4 allele (APOε4+). We found class “C” evidence (possibly effective) for improvement of non-motor features and class “U” evidence (unproven) for motor features in individuals with Parkinson's disease. The number of trials in Parkinson's disease is very small with best evidence that acute supplementation holds promise for improving exercise endurance. Limitations of the literature to date include the range of ketogenic interventions currently assessed in the literature (i.e., primarily diet or medium-chain triglyceride interventions), with fewer studies using more potent formulations (e.g., exogenous ketone esters). Collectively, the strongest evidence to date exists for cognitive improvement in individuals with mild cognitive impairment and in individuals with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele. Larger-scale, pivotal trials are justified in these populations. Further research is required to optimize the utilization of ketogenic interventions in differing clinical contexts and to better characterize the response to therapeutic ketosis in patients who are positive for the apolipoprotein ε4 allele, as modified interventions may be necessary.
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影响因子：
4.5
作者：
Henderson, Samuel T.;Vogel, Janet L.;Costantini, Lauren C.
通讯作者：
Costantini, Lauren C.
影响因子：
4.2
作者：
Imamura, Keiko;Takeshima, Takao;Nakashima, Kenji
通讯作者：
Nakashima, Kenji
影响因子：
4
作者：
de la Rubia Orti, Jose Enrique;Pilar Garcia-Pardo, Maria;Yang, Ivan Hu
通讯作者：
Yang, Ivan Hu
影响因子：
14
作者：
Fortier, Melanie;Castellano, Christian-Alexandre;Cunnane, Stephen C.
通讯作者：
Cunnane, Stephen C.
DOI：
10.2967/jnumed.111.089946
发表时间：
2011-06
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Bohnen NI;Koeppe RA;Minoshima S;Giordani B;Albin RL;Frey KA;Kuhl DE
通讯作者：
Kuhl DE