Circadian Disruption Associated with Alzheimer’s Disease
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Alzheimer’s disease (AD) is increasing in prevalence and has a significant impact on caregivers and the healthcare system. One of the many physiologic process affected by AD is the circadian system, with disruption reflected in abnormalities of the sleep-wake cycle. This interaction is bidirectional, with circadian and sleep disruption influencing disease progression. Understanding the bidirectional relationship between AD and circadian disruption may allow for earlier recognition of the potential to develop dementia as well as improved targeted approaches for therapy. Therapies including melatonin and bright light therapy may be advantageous in improving sleep and circadian rhythms and preventing the progression of disease. However, unfortunately, these modalities are not curative, and additional research is needed to improve treatment options for these individuals.
KeywordsAlzheimer’s disease Circadian disruption β-Amyloid Melatonin Bright light therapy
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Yumna Saeed and Sabra M. Abbott declare that they have no conflict of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 3.Pistacchi M, Gioulis M, Contin F, Sanson F, Marsala SZ. Sleep disturbance and cognitive disorder: epidemiological analysis in a cohort of 263 patients. Neurological Sciences: official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2014;35:1955–62.CrossRefGoogle Scholar
- 20.Peyron C, Tighe DK, van den Pol AN, et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci Off J Soc Neurosci. 1998;18:9996–10015.Google Scholar
- 22.Gerdin MJ, Masana MI, Rivera-Bermudez MA, et al. Melatonin desensitizes endogenous MT2 melatonin receptors in the rat suprachiasmatic nucleus: relevance for defining the periods of sensitivity of the mammalian circadian clock to melatonin. FASEB Journal: official publication of the Federation of American Societies for Experimental Biology. 2004;18:1646–56.CrossRefGoogle Scholar
- 38.Song Q, Feng G, Huang Z, Chen X, Chen Z, Ping Y. Aberrant axonal arborization of PDF neurons induced by Abeta42-mediated JNK activation underlies sleep disturbance in an Alzheimer’s model. Mol Neurobiol. 2016.Google Scholar
- 43.Kang JE, Lim MM, Bateman RJ, et al. Amyloid-beta dynamics are regulated by orexin and the sleep-wake cyclee. Science (New York, NY) 2009; 326:1005–1007.Google Scholar
- 63.Colwell CS, Kaufman CM, Menaker M. Phase-shifting mechanisms in the mammalian circadian system: new light on the carbachol paradox. J Neurosci Off J Soc Neurosci. 1993;13:1454–9.Google Scholar
- 72.Forrestel AC, Miedlich SU, Yurcheshen M, Wittlin SD, Sellix MT. Chronomedicine and type 2 diabetes: shining some light on melatonin. Diabetologia. 2016.Google Scholar
- 79.• van Maanen A, Meijer AM, van der Heijden KB, Oort FJ. The effects of light therapy on sleep problems: a systematic review and meta-analysis. Sleep Med Rev. 2016;29:52–62. A recent systematic review and meta-analysis looking at the effects of light therapy in circadian rhythm sleep disorders, insomnia, AD, and dementia. Eleven studies included patients with AD/dementia and a total of N = 211 patients, demonstrated significant effects of light therapy in patients with AD/dementia in improving sleep onset latency, total sleep time, time in bed, sleep efficiency, and sleep quality. However, there was no significant improvement seen in wake after sleep onset or early morning awakenings. CrossRefPubMedGoogle Scholar
- 80.Forbes D, Blake CM, Thiessen EJ, Peacock S, Hawranik P. Light therapy for improving cognition, activities of daily living, sleep, challenging behaviour, and psychiatric disturbances in dementia. Cochrane Database Syst Rev. 2014: Cd003946Google Scholar
- 84.• Wang YY, Zheng W, Ng CH, Ungvari GS, Wei W, Xiang YT. Meta-analysis of randomized, double-blind, placebo-controlled trials of melatonin in Alzheimer’s disease. International Journal of Geriatric Psychiatry. 2017;32:50–7. A recent meta-analysis looking at the effects of melatonin in AD. Seven studies included patients with AD and a total of N = 462 patients, with the administration of melatonin dosage ranging from 1.5 to 10 mg, from 10 days to 24 weeks, demonstrated that patients receiving melatonin treatment showed prolonged total sleep time at night. Melatonin, however, did not improve cognitive abilities assessed by the mini-mental state examination (MMSE) or the Alzheimer’s Disease Assessment Cognitive Subscale (ADACS). CrossRefPubMedGoogle Scholar
- 89.Camargos EF, Louzada LL, Quintas JL, Naves JO, Louzada FM, Nobrega OT. Trazodone improves sleep parameters in Alzheimer disease patients: a randomized, double-blind, and placebo-controlled study. The American Journal of Geriatric Psychiatry: official journal of the American Association for Geriatric Psychiatry. 2014;22:1565–74.CrossRefGoogle Scholar