Melatonin and Sleep Disturbances in Alzheimer’s Disease

Abstract

: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by sleep, behavioral, memory, and cognitive deteriorations. Sleep disturbance (SD) is a major disease burden in AD which has a reciprocal relationship with AD pathophysiology. It aggravates memory, behavioral, and cognitive complications in AD. Different studies found that melatonin hormone levels reduce even in the pre-clinical stages of AD. Melatonin is the primary sleep-regulating hormone and a potent antioxidant with neuroprotective roles. The decrease in melatonin levels can thus promote SD and AD neuropathology. Exogenous melatonin has the potential to alleviate neuropathology and SD in AD by different mechanisms. Various studies have been conducted so far that assessed the efficacy of exogenous melatonin to treat SD in AD. Though most of the studies suggest that melatonin is useful to ameliorate SD in AD, the remaining studies show opposite results. The timing, dosage, and duration of melatonin administration along with disease condition, genetic, environmental, and some other factors can be responsible for the discrepancies between the studies. More extensive trials with longer durations and higher dosage forms and studies including bright light therapy and melatonin agonists (ramelteon, agomelatine, and tasimelteon) should be performed to determine the efficacy of melatonin to treat SD in AD.

Sleep–Wake Disorders in Alzheimer’s Disease: A Review

“…Tg2576 rats treated with melatonin confirmed that melatonin could augment the clearance of Aβ through the lymphatic system . Furthermore, melatonin agonists (e.g., ramelteon and agomelatine) could improve the sleep quality in the sleep disorders of AD …”

“…The accumulation of tau may regulate the level of orexins . Melatonin may be a modifier in the pathogenesis of AD, and it can improve the sleep–wake cycle and decrease AD development. , It is worth studying the relationship between the LC-NE system and inflammation. Notably, some receptors of these neurotransmitters may be involved in the pathological progress of AD and be worth further investigation.…”

Correlation between vitamin D and poor sleep status in restless legs syndrome

“…The anti-inflammatory effects of vitamin D may be another explanation for vitamin D deficiency that can lead to sleep disorder in the disease. Additionally, the production of melatonin can be regulated by vitamin D ( 13 ), which is the primary sleep-regulating hormone ( 52 ). Several lines of evidence reveal that melatonin can benefit patients with sleep disorders related to various neurological disorders ( 53 , 54 ).…”

Therapeutic Approach to Alzheimer’s Disease: Current Treatments and New Perspectives

“…It has been shown that sleep disorders have a bidirectional relationship with the pathophysiology of AD, worsening the behavioral, cognitive, and memory alterations associated with this disease by increasing the β-amyloid load in response to an inflammatory process induced by these sleep disturbances [145]. In relation to this parameter, a field that has gained great interest in recent years focuses on the neuroprotective role of melatonin, as a reduction of this hormone has been observed in the early stages of AD [146]. Melatonin modulates the expression and function of secretase, thereby inhibiting the amyloidogenic processing of APP and Aβ production.…”