营养不良与阿尔茨海默病相互作用影响的研究进展

The research advance on the interaction between malnutrition and Alzheimer’s disease

阿尔茨海默病(AD)作为衰老相关疾病,也是老年期最常见的痴呆病因,现已成为公共卫生管理日益严峻的挑战。AD发病机制复杂不清,迄今为止仍无明确治疗药物靶向某一通路延缓,甚至阻止疾病进程。过去20年间,单一药物靶向清除β淀粉样蛋白和tau病理改变的临床试验均以失败告终,提示AD作为多病因、多病理机制相互作用的复杂脑疾病,应重视多维度预防和治疗。近年来,肠道菌群通过参与衰老、免疫、代谢等过程,与中枢神经系统不断产生联系,成为AD发生、发展的热点机制。膳食营养作为影响肠道菌群最直接最广泛的环境因素,可通过行为、遗传、免疫、代谢、血管等多条生物学途径影响AD相关认知症状,为实现AD多靶点综合干预提供了新的思路。尽管有一定的研究基础,国内外关于营养与AD的认识仍十分不足,相关研究证据多局限于初步、小样本以及广泛痴呆类型。营养不良究竟是AD发生、发展的危险因素/病因还是AD相关认知或精神行为症状的结果仍不十分清楚。鉴于此,本文综述国内外近10年的最新研究成果,梳理AD患者出现营养不良的原因以及营养不良加重AD发生、发展的研究进展与差距,为AD临床诊疗和进一步探索提供方向。

Alzheimer’ s disease( AD), an aging-related neurodegenerative disease and the leading cause of dementia in the elderly, represents sharply escalating challenge to public health management. The underlying mechanisms of AD are uncertain, which causes the optimal strategies to delay or even prevent the disease progression yet to be established. Over the past two decades, clinical trials of single-agent drugs targeting amyloid-beta and tau pathologies have frequently failed to cure AD, suggesting that as a complex brain disease with multiple causes and pathological mechanisms, AD should be paid attention to multi-dimensional prevention and treatment. In recent years, gut-microbiota connecting with the central nervous system through bidirectional communication with aging,immune, and metabolic pathways has become a hot mechanism for AD. As the most direct and extensive environmental factor affecting gut microbiota, dietary nutrition can affect AD related cognitive symptoms through behavioural, genetic, systemic, immune, metabolic and vascular factors, which provides new insights into comprehensive multi-targeted intervention strategies of AD. Despite accumulating knowledge, the understanding of nutrition and AD is still insufficient, and current research evidence is mostly limited to preliminary, small samples and various dementia types. Whether malnutrition is a risk factor/cause of AD or the result of AD-related cognitive or psychobehavioral symptoms remain unclear. Thus, this review summarizes the evidence in the past decade on the cause of malnutrition in AD patients and malnutrition risking the onset and progression of AD, emphasizing knowledge gaps and providing direction for clinical diagnosis and treatment of AD and further exploration.