A Multimodal Framework for Alzheimer’s Prevention: Diet, Exercise, Fasting, Sleep, and Gut Microbiota

Summary

This narrative review integrates mechanistic and clinical evidence across five modifiable lifestyle domains—exercise, diet, intermittent fasting, sleep, and gut microbiota—as integrated strategies for Alzheimer's disease prevention. The authors present pathophysiological mechanisms by which each intervention modulates neuroinflammation, metabolic dysfunction, and neurodegeneration, with emphasis on synergistic effects of combined approaches exceeding individual interventions. The review acknowledges evidence gaps but proposes multidomain lifestyle optimisation as a promising strategy for delaying cognitive decline in the absence of disease-modifying pharmacotherapies.

Regional applicability

The review synthesises global mechanistic and translational evidence with clinical studies, making findings applicable to United Kingdom healthcare and public health practice. Dietary interventions (Mediterranean, MIND) and exercise guidance are readily adaptable to UK populations; applicability of fasting and sleep interventions may require adaptation to individual circumstances and clinical supervision in older adults at dementia risk.

Key measures

Mechanisms of neuroprotection via BDNF–TrkB signalling, hippocampal neurogenesis, synaptic plasticity, myokines (CTSB, IGF-1, GPLD1), oxidative stress, amyloid-β deposition, mitochondrial efficiency, autophagy (AMPK, SIRT3, Nrf2), short-chain fatty acids, glymphatic clearance, amyloid and tau accumulation

Outcomes reported

The review synthesises evidence on how diet (Mediterranean, MIND, ketogenic), exercise (aerobic, anaerobic, resistance), intermittent fasting, sleep quality, and gut microbiota modifications influence cognitive ageing and Alzheimer's disease pathology through mechanistic pathways including BDNF signalling, autophagy, microbiota-derived metabolites, and glymphatic clearance.

Supporting research

Author abstract gives substantive Mediterranean/MIND/ketogenic diet and fasting mechanisms within a multimodal Alzheimer prevention review.

Limits: This is a mixed mechanistic/translational review, not a completed randomised dietary intervention. Synergy and preventive efficacy in diverse humans are not independently validated.

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