Nutrition in Alzheimer's disease: a review of an underappreciated pathophysiological mechanism

Alzheimer's disease (AD) is the leading cause of dementia in older individuals and is an escalating challenge to global public health. Pharmacy therapy of AD is one of the well-funded areas; however, little progress has been made due to the complex pathogenesis. Recent evidence has demonstrated that modifying risk factors and lifestyle may prevent or delay the incidence of AD by 40%, which suggests that the management should pivot from single pharmacotherapy toward a multipronged approach because AD is a complex and multifaceted disease. Recently, 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 cognition in AD-related dementia directly or indirectly through complex interactions of behavioral, genetic, systemic, and brain factors. Thus, considering the multiple etiologies of AD, nutrition represents a multidimensional factor that has a profound effect on AD onset and development. However, mechanistically, the effect of nutrition on AD is uncertain; therefore, optimal strategies or the timing of nutritional intervention to prevent or treat AD has not been established.Thus, this review summarizes the current state of knowledge concerning nutritional disorders, AD patient and caregiver burden, and the roles of nutrition in the pathophysiology of AD. We aim to emphasize knowledge gaps to provide direction for future research and to establish optimal nutrition-based intervention strategies for AD.