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Page: Circadian Rhythm

Neurodegenerative disease
Neurodegenerative disease has been associated with disrupted circadian rhythms. Patients with mild cognitive impairment (MCI) were shown to have advanced secretion of melatonin, awoke more frequently after sleep onset and had a higher delay to rapid eye movement sleep. This suggests that patients that are more susceptible to dementia, especially the elderly, are likely to have disrupted circadian rhythms even without a neurodegenerative disease.

Alzheimer's Disease
Over 40% of Alzheimer's Disease patients display symptoms of circadian misalignment, including sundowning, excessive daytime sleepiness, nocturnal wandering, and day-night reversal.

Multiple Sclerosis
Fatigue is an important cause of disability in Multiple Sclerosis (MS) pathogenesis, and is found in about 64% of patients. Studies have recorded sleep disturbance and insomnia in about 58% of patients and is associated with symptoms such as pain and nocturia. Although the exact cause is unclear, one proposed mechanism of this phenomenon is the disruption of circadian rhythms. Multiple Sclerosis has also been associated with abnormal circadian rhythms in body temperature and subsequently periodic hyperthermia.

Disruption
Circadian rhythm dysfunction has been shown to contribute to the progression of neurodegenerative disease. Disruption of rhythms in the secretion of melatonin has direct effects on normal brain aging and neuropathological aging due to melatonin's roles in regulating energy metabolism through signaling pathways with insulin and modulating epigenetics. Circadian dysfunction is also thought to contribute to Alzheimer's disease pathogenesis through changes in amyloid-β deposition. Accumulation of amyloid-β plaques in the brain is an important step in the progression of Alzheimer's, and human models show that amyloid-β concentrations rise during wakefulness and fall during sleep. Disrupted sleep patterns may contribute directly to the worsening of AD through disruption of the natural rise and fall of amyloid-β.

Manipulation of rhythms as therapy
It is hypothesized that the modulation of circadian rhythms through behavioral intervention could help alleviate symptoms of neurodegenerative disease. The role of sleep in the aging brain suggests that using strict schedules for sleeping coupled with scheduled lighting could help to slow the progression of Alzheimer's. Research also suggests that using another zeitgeber, food, may be useful in treating Alzheimer's symptoms through use of Ghrelin. Ghrelin is a hormone synthesized in the stomach which acts in the pituitary to stimulate energy homeostasis, cortisol release, appetite, and weight gain, and is seen to rise just prior to eating. Administering Ghrelin to patients daily could help amplify the effects of food-entrainment to scheduled daily meals, somewhat restoring circadian rhythmicity and benefitting Alzheimer’s patients.