针对受损的营养感应，用重新定位的疗法来预防或治疗与年龄相关的认知能力下降和痴呆症：系统评价。
Targeting impaired nutrient sensing with repurposed therapeutics to prevent or treat age-related cognitive decline and dementia: A systematic review.
机构信息
Department of Medicine and Aged Care, @AgeMelbourne, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia; University Hospital Geelong, Barwon Health, Melbourne, Victoria, Australia.
Department of Medicine and Aged Care, @AgeMelbourne, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia; Centre for Quantitative Neuroimaging, Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
出版信息
Ageing Res Rev. 2021 May;67:101302. doi: 10.1016/j.arr.2021.101302. Epub 2021 Feb 17.
BACKGROUND
Dementia is a debilitating syndrome that significantly impacts individuals over the age of 65 years. There are currently no disease-modifying treatments for dementia. Impairment of nutrient sensing pathways has been implicated in the pathogenesis of dementia, and may offer a novel treatment approach for dementia.
AIMS
This systematic review collates all available evidence for Food and Drug Administration (FDA)-approved therapeutics that modify nutrient sensing in the context of preventing cognitive decline or improving cognition in ageing, mild cognitive impairment (MCI), and dementia populations.
METHODS
PubMed, Embase and Web of Science databases were searched using key search terms focusing on available therapeutics such as 'metformin', 'GLP1', 'insulin' and the dementias including 'Alzheimer's disease' and 'Parkinson's disease'. Articles were screened using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). The risk of bias was assessed using the Cochrane Risk of Bias tool v 2.0 for human studies and SYRCLE's risk of bias tool for animal studies.
RESULTS
Out of 2619 articles, 114 were included describing 31 different 'modulation of nutrient sensing pathway' therapeutics, 13 of which specifically were utilized in human interventional trials for normal ageing or dementia. Growth hormone secretagogues improved cognitive outcomes in human mild cognitive impairment, and potentially normal ageing populations. In animals, all investigated therapeutic classes exhibited some cognitive benefits in dementia models. While the risk of bias was relatively low in human studies, this risk in animal studies was largely unclear.
CONCLUSIONS
Modulation of nutrient sensing pathway therapeutics, particularly growth hormone secretagogues, have the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.
背景
痴呆症是一种使人虚弱的综合征，对 65 岁以上的人影响显著。目前尚无针对痴呆症的疾病修正治疗方法。营养感应途径的损伤与痴呆症的发病机制有关，可能为痴呆症提供一种新的治疗方法。
目的
本系统评价汇集了所有关于美国食品和药物管理局（FDA）批准的治疗方法的现有证据，这些治疗方法可改变营养感应，以预防认知能力下降或改善衰老、轻度认知障碍（MCI）和痴呆人群的认知能力。
方法
使用重点关注现有治疗方法的关键搜索词，如“二甲双胍”、“GLP1”、“胰岛素”以及包括“阿尔茨海默病”和“帕金森病”在内的各种痴呆症，在 PubMed、Embase 和 Web of Science 数据库中进行检索。使用 Covidence 系统评价软件（澳大利亚墨尔本 Veritas Health Innovation）筛选文章。使用 Cochrane 人类研究偏倚风险工具 v 2.0 和 SYRCLE 动物研究偏倚风险工具评估偏倚风险。
结果
在 2619 篇文章中，有 114 篇文章描述了 31 种不同的“营养感应途径调节”治疗方法，其中 13 种专门用于人类干预试验，用于正常衰老或痴呆症。生长激素促分泌素改善了人类轻度认知障碍和可能的正常衰老人群的认知结果。在动物中，所有研究的治疗类别在痴呆症模型中都表现出一些认知益处。虽然人类研究的偏倚风险相对较低，但动物研究的偏倚风险在很大程度上并不清楚。
结论
营养感应途径治疗方法的调节，特别是生长激素促分泌素，有可能改善认知结果。总的来说，从动物模型到人类群体的转化明显不足。
Zotero 插件