Linkage of circadian rhythm disruptions with Alzheimer's disease and therapeutic interventions.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and pathological brain changes. While aging is the primary risk factor, circadian rhythm disruption (CRD) is increasingly recognized as a central driver of AD pathology. CRD exacerbates oxidative stress, systemic inflammation, and gut microbiome dysbiosis, impairing sleep-wake cycles, disrupting metabolic homeostasis, and promoting neuroinflammation, ultimately accelerating disease progression. Oxidative stress, a key factor in neuronal damage, is both a cause and consequence of circadian misalignment, while mitochondrial dysfunction further amplifies oxidative damage, impairing synaptic function and cognitive stability. Additionally, gut microbiome dysbiosis contributes to neuroinflammatory processes, worsening neurodegeneration. Given these complex interactions, this review aims to elucidate the role of CRD in AD pathology and explore potential therapeutic interventions targeting circadian dysfunction. Specifically, it examines the efficacy of time-restricted feeding (TRF), a dietary strategy that aligns food intake with circadian rhythms. TRF has shown promise in restoring circadian function, reducing oxidative stress, improving mitochondrial health, and promoting gut microbiome diversity. By addressing CRD, TRF may offer a novel approach to mitigating AD pathologies. This review also identifies current research gaps and future directions for developing circadian-based interventions in AD prevention and treatment.