Human Health[edit]

Neurodegenerative disease[edit]
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.[1] 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[edit]
Over 40% of Alzheimer's Disease patients display symptoms of circadian misalignment,
including sundowning, excessive daytime sleepiness, nocturnal wandering, and day-night
reversal.[1]
Multiple Sclerosis[edit]
Fatigue is an important cause of disability in Multiple Sclerosis (MS) pathogenesis, and is found
in about 64% of patients. [2] 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.
[2]
Multiple Sclerosis has also been associated with abnormal circadian rhythms in body
temperature and subsequently periodic hyperthermia. [3]

Disruption[edit]
Circadian rhythm dysfunction has been shown to contribute to the progression of
neurodegenerative disease.[4] 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.[5]
Circadian dysfunction is also thought to contribute to Alzheimer's disease pathogenesis through
changes in amyloid- deposition. Accumulation of amyloid- plaques in the brain is an
important step in the progression of Alzheimer's, and human models show that amyloid-
concentrations rise during wakefulness and fall during sleep.[4] Disrupted sleep patterns may
contribute directly to the worsening of AD through disruption of the natural rise and fall of
amyloid-.

Manipulation of rhythms as therapy[edit]

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.[6] 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.[7] Administering Ghrelin
to patients daily could help amplify the effects of food-entrainment to scheduled daily meals,
somewhat restoring circadian rhythmicity and benefitting Alzheimers patients.[7]

1. ^ Jump up to: a b Oritz-Tuldela E, Martinez-Nicolas A, Diaz-Mardomingo C, Garcia-Herranz S,

Pereda-Perez I, Valencia A, Peraita H, Venero C, Madrid J, Rol M. 2014. The Characterization of
Biological Rhythms in Mild Cognitive Impairment. BioMed Research International.
2. ^ Jump up to: a b Stanton BR, Barnes F, Silber E. 2006. Sleep and fatigue in multiple sclerosis.
Multiple Sclerosis 12:481-486
3. Jump up ^ Martinez-Rodriguez JE, Muntesis E, Roquer J. 2006. Periodic hyperthermia and
abnormal circadian temperature rhythm in a patient with multiple sclerosis. Multiple Sclerosis
12:515-517.
4. ^ Jump up to: a b Lucey BP, Bateman RJ. March 2014 Amyloid-B diurnal pattern: possible role of
sleep in Alzheimers disease (AD) pathogenesis. Neurobiology of Aging 35:529-534.
5. Jump up ^ Jenwitheesuk A, Nopparat C, Mukda S, Wongchitrat P, Govitrapong P. 2014
Melatonin Regulates Aging and Neurodegeneration through Energy Metabolism, Epigenetics,
Autophagy and Circadian Rhythm Pathways. International Journal of Molecular Sciences
15:16848-16884.
6. Jump up ^ Figueiro MG, Plitnick BA, Lok A, Jones GE, Higgins P, Hornick TR, Rea MS.
September 2014. Tailored lighting intervention improves measures of sleep, depression and
agitation in persons with Alzheimers disease and related dementia living in long-term care
facilities. Clinical Interventions in Aging.
7. ^ Jump up to: a b Kent BA. September 2014. Synchronizing an aging brain: can entraining
circadian clocks by food slow Alzheimers disease? Frontiers in Aging Neuroscience.