Nutritional interventions for preventing cognitive decline in patients with mild cognitive impairment and Alzheimer's disease: A comprehensive network meta-analysis and Mendelian Randomization study

IF 2.9 Q3 NUTRITION & DIETETICS

Clinical nutrition ESPEN Pub Date : 2025-03-25 DOI:10.1016/j.clnesp.2025.03.040

Qian He , Adam N. Bennett , Chuyun Zhang , Jia Yue Zhang , Shuyao Tong , Kei Hang Katie Chan

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引用次数: 0

Abstract

Background

As the population ages rapidly, cognitive impairment, especially in conditions like Alzheimer's disease (AD) and mild cognitive impairment (MCI), has become a crucial public health issue. Nutritional interventions have garnered attention as a promising non-pharmacological strategy for maintaining cognitive function and decelerating its decline.

Objective

This study aimed to evaluate the effectiveness of various nutritional interventions in preventing cognitive impairment and elucidate intricate biological pathways linking nutritional interventions to cognitive function through a comprehensive approach involving systematic review, network meta-analysis (NMA), and Mendelian randomization (MR) analysis.

Methods

We utilized pair-wise comparisons and NMA to evaluate the efficacy of different nutritional interventions on cognitive function in patients with decreased cognitive abilities. A systematic search in three biomedical databases was performed for double-blinded, randomized controlled trials (RCTs) or head-to-head comparisons up to December 31, 2024. The NMA has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022331173). Moreover, to clarify the biological mechanisms linking nutritional interventions to cognitive impairment, we conducted two-sample MR analyses to assess the potential causal relationships between 9 genetically predicted nutrient levels derived from extensive genome-wide association studies (GWASs) and 12 biomarkers linked to brain aging.

Results

This study encompassed 52 trials with 8452 participants, 9 GWASs examining genetically predicted nutrient levels with a total of 603,996 participants, and 12 GWASs investigating brain aging biomarkers with a total of 2,405,530 participants. The NMA demonstrated that the multi-ingredient intervention outperformed other interventions significantly (standardized mean difference [SMD] = 2.03; 95 % credible interval [95 % CrI] = 0.97–3.09, P = 0.0002). In the MR analysis, the findings indicated that the multi-ingredient intervention was linked to reduced C-reactive protein (CRP) levels (odds ratios [OR] = 0.96, 95 % confidence interval [95 % CI] = 0.93–0.99, P = 0.014), suggesting that the multi-ingredient intervention may mitigate cognitive impairment by reducing inflammation.

Conclusions

Our NMA amalgamated evidence underscoring multi-ingredient interventions as the most efficacious strategy for attenuating cognitive decline in individuals with MCI and AD. Furthermore, the MR analysis unveiled the mechanisms underpinning the protective effects of multi-ingredient interventions, potentially offering benefits even in the early stages of neurodegeneration by mitigating oxidative stress and inflammation.

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预防轻度认知障碍和阿尔茨海默病患者认知能力下降的营养干预：综合网络荟萃分析与孟德尔随机研究》（Comprehensive Network Meta-Analysis and Mendelian Randomization Study）。

背景：随着人口快速老龄化，认知障碍，尤其是阿尔茨海默病（AD）和轻度认知障碍（MCI），已成为一个重要的公共卫生问题。营养干预作为一种维持认知功能和减缓其衰退的有前途的非药物策略已经引起了人们的注意。目的：本研究旨在通过系统综述、网络荟萃分析（NMA）和孟德尔随机化（MR）分析等综合方法，评估各种营养干预在预防认知功能障碍方面的有效性，并阐明营养干预与认知功能之间复杂的生物学途径。方法：采用两两比较和NMA评价不同营养干预对认知能力下降患者认知功能的影响。系统检索三个生物医学数据库，进行双盲、随机对照试验（rct）或头对头比较，截止到2024年12月31日。NMA已在国际前瞻性系统评价登记册(PROSPERO；CRD42022331173)。此外，为了阐明营养干预与认知障碍之间的生物学机制，我们进行了两样本孟德尔随机化（MR）分析，以评估来自广泛全基因组关联研究（GWASs）的9种遗传预测营养水平与12种与脑衰老相关的生物标志物之间的潜在因果关系。结果：该研究包括52项试验，共有8452名参与者，9项GWASs检查基因预测的营养水平，共有603,996名参与者，12项GWASs调查脑衰老生物标志物，共有2,405,530名参与者。NMA表明，多成分干预显著优于其他干预(标准化平均差异[SMD] = 2.03；95%可信区间[95% CrI] = 0.97-3.09, P = 0.0002)。在MR分析中，研究结果表明，多成分干预与降低c反应蛋白（CRP）水平有关（优势比[OR] = 0.96, 95%可信区间[95% CI] = 0.93-0.99, P = 0.014），表明多成分干预可能通过减少炎症来减轻认知障碍。结论：我们的NMA综合了证据，强调多成分干预是减轻MCI和AD患者认知能力下降的最有效策略。此外，磁共振分析揭示了多成分干预保护作用的机制，通过减轻氧化应激和炎症，甚至在神经退行性疾病的早期阶段也可能提供益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical nutrition ESPEN NUTRITION & DIETETICS-

CiteScore

4.90

自引率

3.30%

发文量

512

期刊介绍： Clinical Nutrition ESPEN is an electronic-only journal and is an official publication of the European Society for Clinical Nutrition and Metabolism (ESPEN). Nutrition and nutritional care have gained wide clinical and scientific interest during the past decades. The increasing knowledge of metabolic disturbances and nutritional assessment in chronic and acute diseases has stimulated rapid advances in design, development and clinical application of nutritional support. The aims of ESPEN are to encourage the rapid diffusion of knowledge and its application in the field of clinical nutrition and metabolism. Published bimonthly, Clinical Nutrition ESPEN focuses on publishing articles on the relationship between nutrition and disease in the setting of basic science and clinical practice. Clinical Nutrition ESPEN is available to all members of ESPEN and to all subscribers of Clinical Nutrition.