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.

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.