Nutrition in Alzheimer’s Disease: A Review of an Underappreciated Pathophysiological Mechanism

Abstract

AbstractBackgroundPharmacy therapy of Alzheimer’s disease (AD) is one of the areas that are well funded, but where little progress has been made due to the complex pathogenesis. The gut‐microbiota‐brain axis has gained tremendous traction in the pathogenesis of AD through bidirectional communication with multiple neural, immune, and metabolic pathways, providing new insights into novel therapeutic strategies. Dietary nutrition is an important and profound environmental factor that influences the composition and function of the microbiota. The Nutrition for Dementia Prevention Working group recently found that dietary nutrition can affect the cognition of AD‐related dementia directly or indirectly through complex interactions of behavioral, genetic, systemic, and brain factors. This review aimed to emphasize the knowledge gaps to provide direction for future research and to establish optimal nutrition‐based intervention strategies for AD.MethodThis review discusses the associated evidence between malnutrition and the onset and development of AD for modifying the potentially reversible nutrition‐related risk factors of AD, describe the potential pathogenesis underlying the role of nutrition in the progression of AD and emphasize the current knowledge gaps for further research.ResultThe role and effects that nutrition and diet have on AD are more pervasive than previously believed. We identified and highlighted a novel vicious cycle comprising malnutrition, development of AD, and heavy caregiver burden (Figure 1). As pharmacological approaches demonstrate limited benefits for improving the symptoms of AD, early nutritional intervention for preventing or delaying the progression of AD are worth attempting. The mechanisms underlying the effect of nutrition on the development of AD remain uncertain, including genetics and epigenetics, AD‐specific biomarkers, metabolic pathways, the gut‐microbiota‐inflammation‐brain axis, and their complex interactions (Figure 2).ConclusionThese potential nutrition‐related pathogenic pathways can be exploited as an important environmental factor and could be the focus of targeted AD interventions. Future research is needed to fill in the discussed gaps in knowledge, including prospective studies to identify nutritional biomarkers that can predict AD, multi‐omics studies to elucidate the exact mechanisms by which nutrition influences AD, and clinical trials to identify the best nutritional intervention strategies to prevent and improve cognitive and behavioral disturbances in the AD population.