Nutritional Interventions for the Prevention of Cognitive Decline in Patients With Mild Cognitive Impairment and Alzheimer Disease: Protocol for a Network Meta-Analysis of Randomized Controlled Trials
Authors: He Qian , Wu Kevin Chun Hei , Bennett Adam N , Zhang Jia Yue , Chan Kei Hang Katie 
Published: November 2023

Background
Mild cognitive impairment (MCI) is the stage between cognitive decline due to physiological aging and the severity of decline seen in neurodegenerative disorders like Alzheimer disease (AD), which is among the most prevalent neurodegenerative disorders characterized by cognitive impairment. People with MCI are at increased risk of developing AD. Although MCI and AD are incurable, nutritional interventions can potentially delay or prevent their onset. Consequently, effective interventions used to decelerate or alleviate the progress of cognitive impairment in older people are a significant focus in geriatric care. Given the synergistic effects of nutrition on health, assessing the effectiveness of nutritional supplements or dietary composition in preventing MCI or AD is essential for developing interventional strategies.

Objective
Our study aims to assess the effectiveness of various nutritional interventions, including special dietary types, dietary patterns, specific foods, nutritional intake, and nutritional supplements, in preventing cognitive decline among patients diagnosed with MCI or AD. To achieve this, we will use a comprehensive approach, including network meta-analysis, pairwise meta-analysis, and systematic review of randomized controlled trials (RCTs).

Methods
The review will follow the Population, Intervention, Comparison, Outcome (PICO) model and the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. Two investigators will independently search PubMed electronically. Data extraction will follow the inclusion criteria, and data will be assessed for risk of bias using a revised tool. Additionally, evidence quality will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. The outcomes of interest are assessing the cognitive outcomes in patients with MCI or AD. A systematic literature search will be conducted, identifying randomized controlled trials that investigate the impact of these nutritional interventions on cognitive function decline in individuals with MCI and AD. Network meta-analyses (random-effects model) and pairwise meta-analyses will then estimate the relative effectiveness of different nutritional interventions.

Results
We included 51 studies, published between 1999 and 2023 (27 studies for AD and 24 studies for MCI) and involving 8420 participants. We completed data extraction for all 51 studies by December 2023. Currently, we are actively engaged in data analysis and manuscript preparation. We plan to finalize the manuscript and publish the comprehensive results by the end of 2024.

Conclusions
Our study holds significant clinical relevance given the rising prevalence of AD and the potential influence of nutritional interventions on cognitive function in individuals with MCI and AD. By investigating this relationship, our research aims to inform evidence-based decision-making in the development of prevention strategies for MCI and AD. The outcomes are expected to contribute to the establishment of reliable recommendations for MCI or AD management, providing substantial support in the field.

Trial Registration
PROSPERO CRD42022331173; http://tinyurl.com/3snjp7a4

International Registered Report Identifier (IRRID)
PRR1-10.2196/47196