The link between circadian disruption and Alzheimer’s disease and related dementias: insights from peripheral inflammation

Circadian rhythms are essential for maintaining physiological homeostasis, influencing biological processes from the sleep–wake cycle to metabolism and immune responses. Disruption of these rhythms is increasingly linked to the pathogenesis of Alzheimer’s disease and related dementias (ADRDs), conditions characterized by cognitive decline and neuropsychiatric symptoms through various pathways, including increases in inflammation. While many studies link the effects of circadian disruption on neuroinflammation to ADRDs, this review explores the potential link between the circadian disruption of peripheral inflammation and ADRDs. We discuss the evidence of how circadian misalignment can exacerbate neuroinflammation through the activation of the peripheral immune system. We further examine the role of peripheral factors such as insulin dysregulation, melatonin levels, and gut microbiome imbalances in amplifying these peripheral inflammatory responses. These data underscore the significance of circadian regulation in maintaining immune homeostasis, highlighting potential therapeutic avenues for mitigating ADRDs through the restoration of circadian integrity.