Sundowning refers to behavioral disturbances that are fairly common in Alzheimer's disease and tend to occur in the early evening. For reasons that aren't entirely clear, many people with Alzheimer's exhibit increased confusion, anxiety, agitation and even aggression at the end of the day. Luckily, there's evidence that melatonin can help with sundowning and related sleep disturbances.
Alzheimer's and "Sundowning"
According to the Alzheimer's Association, nearly a fifth of individuals with Alzheimer's will experience periods of sundowning, usually in the middle stages of the disease. Sundowning takes a toll on those who have Alzheimer's and contributes greatly to caregiver stress and fatigue. It reportedly plays a major role in decisions to move those with Alzheimer's from home care to nursing homes.
Melatonin has many roles in the body, but it is particularly important in sleep regulation. Melatonin is produced in the brain, specifically by the pineal gland. This gland releases its peak level of melatonin at dusk, and the hormone appears to be instrumental in the cascade of changes that we call falling asleep.
Alzheimer's and Melatonin
Research has long established that melatonin levels naturally decrease with age, but people with Alzheimer's disease have especially low levels -- sometimes only half as much as people of the same age who don't have the disease. Also, sleep disturbances are frequently a symptom of Alzheimer's. In recent years, a number of studies have reported benefits of supplemental melatonin, not only for reducing Alzheimer's-related sleep problems, but for sundowning as well.
Melatonin may also have further benefits. It's a powerful antioxidant, acting to counter harmful chemical reactions that can damage cells. It appears to have specific neuroprotective qualities, meaning that it helps protect nerve and brain cells from damage. There's also evidence that having an insufficiency of melatonin plays a role in depression.
Some studies suggest that the hormone can improve mild cognitive impairment, although researchers emphasize that the effect is limited and that melatonin isn't a "cure" for full-blown Alzheimer's disease. Some researchers caution that the impact of the hormone would be relatively less in late-stage Alzheimer's.
On the positive side, melatonin has few if any side effects, in large part because it's processed and removed from the body very quickly. However, that quality and the multiplicity of its effects make melatonin less than ideal as a medication.
Researchers have begun developing "melatoninergic" or melatonin-type drugs that are longer-acting and have more specific targets. Rozerem (ramelteon) has won FDA approval for long-term treatment of sleep disturbances. Another drug, Valdoxan (agomelatine), is meant to treat major depressive disorders and is also undergoing clinical trials for FDA approval.
Thus far, no melatonin-type medications have been developed specifically for Alzheimer's disease or sundowning.
What You Can Do
Since melatonin is classified as a supplement, it's available without a prescription. But before you give the hormone to someone with Alzheimer's, you should consult his or her physician, who'll be able to determine whether it makes sense and fits the person's symptoms. Studies of melatonin for treating Alzheimer's have reported benefits from doses of 3 to 9 mg of melatonin per day.Suggested Reading:
Cardinali, Daniel P. "Melatonin. Physiology and Clinical Applications." Vertex 18:74(2007): 288-93. 10 Jul. 2008.
Cardinali, Daniel P., A.M. Furio, M.P. Reyes., "Clinical Perspectives for the use of Melatonin as a Chronobiotic and Cytoprotective Agent." Annals of the New York Academy of Sciences 1057(2005): 327-36. 10 Jul. 2008 <http://www.annalsnyas.org/cgi/content/full/1057/1/327> (subscription).
Cardinali, Daniel P., A.M. Furio, M.P. Reyes, L.I. Brusco, "The Use of Chronobiotics in the Resynchronization of the Sleep-Wake Cycle." Cancer Causes Control 17:4(2006): 601-9. 10 Jul. 2008 <http://www.springerlink.com/content/m4g3027263217433/> (subscription).
Furio, A.M., L.I. Brusco, Daniel P. Cardinali., "Possible Therapeutic Value of Melatonin in Mild Cognitive Impairment: A Retrospective Study." Journal of Pineal Research 43:4(2007): 404-9. 10 Jul. 2008 <http://www3.interscience.wiley.com/search/allsearch?mode=viewselected&product=journal&ID=118521372&> (subscription).
Pandi-Perumal, S.R., V. Srinivasan, B. Poeggeler, R. Hardeland, Daniel P. Cardinali., "Drug Insight: The use of Melatonergic Agonists for the Treatment of Insomnia-Focus on Ramelteon." Nature Clinical Practice Neurology 3:4(2007): 221-8. 10 Jul. 2008 <http://www.nature.com/ncpneuro/journal/v3/n4/full/ncpneuro0467.html;jsessionid=FC5FEC227BC35FCE1C277322F0FB9144>. (subscription).
Sanchez-Barcelo, Emilio J., Carlos M. Martinez-Campa, Maria D. Mediavilla, Alicia Gonzalez, Carolina Alonso-Gonzalez, Samuel Cos. "Melatonin and Melatoninergic Drugs as Therapeutic Agents: Ramelteon and Agomelatine, the Two Most Promising Melatonin Receptor Agonists." Recent Patents on Endocrine, Metabolic & Immune Drug Discovery. 1:2(2007): 142-51. 10 Jul. 2008 <http://www.ingentaconnect.com/content/ben/emi/2007/00000001/00000002/art00006;jsessionid=842f7b60lei3.alexandra?format=print> (subscription).
"Sleeplessness and Sundowning." alz.org. Alzheimer's Association. 16 Oct. 2007. 5 Jul. 2008 <http://www.alz.org/living_with_alzheimers_sleeplessness_and_sundowning.asp>.
Srinivasan V., S.R. Pandi-Perumal, D.P. Cardinali, B. Poeggeler and R. Hardeland. "Melatonin in Alzheimer's Disease and Other Neurodegenerative Disorders." Behavioral and Brain Functions 2:15(2006). 10 Jul. 2008 <http://www.behavioralandbrainfunctions.com/content/2/1/15>.
Wu, Y.H. and D. F. Swaab. "Disturbance and Strategies for Reactivation of the Circadian Rhythm System in Aging and Alzheimer's Disease." Sleep Medicine 8:6(2007):623-36. 10 Jul. 2008 <http://linkinghub.elsevier.com/retrieve/pii/S1389-9457%2806%2900683-6> (subscription).