Lifestyle-Based Multimodal Prevention Strategies for Alzheimer’s Disease : Curr Alzheimer Res | May 2026

Introduction

Alzheimer’s disease (AD) is increasingly recognized as a multifactorial disorder driven by complex interactions among genetic susceptibility, metabolic dysfunction, neuroinflammation and environmental exposures. With currently available pharmacotherapies offering only modest disease modification, attention has shifted toward preventive lifestyle-based interventions targeting multiple biological pathways involved in cognitive decline.

Problem Statement

Single-domain interventions such as isolated dietary modification or exercise alone may provide limited protection against neurodegeneration. A major challenge in preventive neurology is defining integrated multimodal strategies capable of simultaneously addressing metabolic, inflammatory, vascular and neurodegenerative mechanisms underlying Alzheimer’s disease progression.

Summary

This comprehensive review proposes a multidomain framework for Alzheimer’s prevention integrating physical activity, nutrition, intermittent fasting, sleep optimization and gut microbiome modulation. Exercise emerged as a central neuroprotective intervention, with aerobic and resistance training shown to enhance hippocampal neurogenesis, synaptic plasticity and neuronal resilience through activation of BDNF–TrkB signaling and exercise-induced myokines such as IGF-1 and cathepsin B. Dietary approaches including Mediterranean, MIND and ketogenic diets demonstrated potential to reduce oxidative stress, improve mitochondrial efficiency and attenuate amyloid-related neurotoxicity, particularly in metabolically vulnerable APOE4 carriers. Intermittent fasting was highlighted as an additional metabolic intervention capable of promoting ketone utilization, autophagy activation and angiogenesis while simultaneously reshaping gut microbial composition. The review also underscores the growing importance of the gut–brain axis, where microbial metabolites including short-chain fatty acids and tryptophan derivatives may modulate neuroinflammation and neuronal survival. Sleep quality, particularly preservation of slow-wave sleep architecture, was identified as another key determinant of cognitive health through facilitation of glymphatic clearance of amyloid-β and tau proteins. Importantly, the authors emphasize that these interventions likely exert synergistic rather than isolated effects, supporting a precision lifestyle medicine approach for dementia prevention. The review also identifies major research gaps, including optimal intervention intensity, long-term adherence strategies and individualized protocols for genetically high-risk populations.