Melatonin as Supplemental Treatment
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A groundbreaking trial, conducted by CPS Research, is the first of its kind to investigate the use of sleep hormone melatonin as an add-on treatment for dementia.
"We aim to establish that melatonin helps combat sleeplessness in dementia patients; that a restful and undisturbed sleep helps patients with dementia function better daily and that taking melatonin makes the symptoms of dementia less severe,” said Dr. Gordon Crawford of CPS Research.
What is Melatonin?
Melatonin is a natural hormone in the body that helps regulate our cyrcadian rythm.
People take melatonin supplements to fight insomnia and circadian rhythm sleep disorders. Prolonged release melatonin has shown good results in treating insomnia in adults over 55.[1]
Dr. Crawford explained, “Melatonin does not currently exist as a treatment for dementia but is registered in Europe and the UK for use in older patients. It has proven remarkably safe and virtually free from side effects."
Sundowning & Melatonin
45% of people with dementias such as Alzheimer's suffer from "sundowning," which often causes heightened afternoon agitation.[2] (For more information on sundowning, click here.) Not getting enough melatonin is a suspected cause.
There is a clear connection behind this suspicion. In Alzheimer's, the two hallmarks of the disease are amyloid plaques and neurofibrillary tangles (Tangles, for short). In a person with Alzheimer's, these tangles can be found in the part of the brain called the hypothalamus. Tangles in the hypothalamus adversely affect the body's production of melatonin. The implication is that Alzheimer's dries up melatonin production. This throws a wrench into the body's daily rhythm.
To make things worse, a vicious cycle ensues. Melatonin has been shown to prevent hyperphosphorylation of the tau protein in rats. In other words, melatonin prevents tangles.[3]
Therefore, less melatonin means less "tangle-prevention." The result is even more Alzheimer's tangles which means even less melatonin. This cycle could well be why many studies have shown that sundowning can be effectively treated with melatonin supplements in the evening.[4]
Amyloid Plaque & Melatonin
The first published evidence that melatonin may be useful in fighting dementias such as Alzheimer's was the demonstration that this neurohormone prevents neuronal death caused by exposure to the amyloid beta protein. Amyloid beta is a neurotoxic substance that is poisonous to brain cells.
Melatonin also inhibits the aggregation of the amyloid beta protein into neurotoxic microaggregates. These "toxic bunches" form the "plaque" characteristic of full-blown Alzheimer's. By blocking this bunching up of amyloid beta, melatonin helps fight plaque.[5]
What It Isn't & What It Is
Melatonin is not an all-purpose sleeping pill.
A 2006 review found "no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder."[6]
Melatonin is:
- mostly about entraining the circadian clock to get people on a healthy daily cycle
- about helping to fight insomnia.[8]
The Melatonin-Dementia Study
CPS Research is conducting a study in Scotland using a slow-release melatonin medicine (which is already marketed) and are looking for Alzheimer's disease patients who are having trouble sleeping. We will arrange for a full assessment of their general health and sleeping patterns. Suitable patients will be offered access to a study assessing the treatment of sleep disturbance in Alzheimer's disease with slow-release melatonin for up to six months.
For more information please contact one of our research nurses on 0800 085 6029 or send an email to sleep@cpsresearch.co.uk
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More Information
1. Wade AG, Ford I, Crawford G (October 2007). "Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes". Curr Med Res Opin 23 (10): 2597-605. doi:10.1185/030079907X233098. PMID 17875243.
2. "Disruptive behavior as a predictor in Alzheimer disease" (Arch. Neurol. 64 (12): 1755-61. doi:10.1001/archneur.64.12.1755. PMID 18071039. by Scarmeas N, Brandt J, Blacker D, et al., December 2007)
3. Wang X, Zhang J, Yu X, Han L, Zhou Z, Zhang Y, Wang J (2005). "Prevention of isoproterenol-induced tau hyperphosphorylation by melatonin in the rat". Sheng Li Xue Bao 57 (1): 7-12. PMID 15719129.
4. Volicer L, Harper D, Manning B, Goldstein R, Satlin A (2001). "Sundowning and circadian rhythms in Alzheimer's disease". Am J Psychiatry 158 (5): 704-11. doi:10.1176/appi.ajp.158.5.704. PMID 11329390.
5. Pappolla MA, Sos M, Omar RA, Bick RJ, Hickson-Bick DL, Reiter RJ, Efthimiopoulos S, Robakis NK. (1997). "Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide". J Neurosci 17 (5): 1683-1690. PMID 9030627.
6. Buscemi, Nina; Vandermeer, B; Hooton, N; Pandya, R; Tjosvold, L; Hartling, L; Vohra, S; Klassen, TP et al. (2006-02-18). "Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis" (HTML: Full text). BMJ 332 (7538): 385-393. doi:10.1136/bmj.38731.532766.F6. PMID 16473858. PMC 1370968. http://www.bmj.com/content/332/7538/385.full. Retrieved 2008-05-17.
7. Buscemi N, Vandermeer B, Hooton N, et al. (December 2005). "The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis". Journal of General Internal Medicine 20 (12): 1151-8. doi:10.1111/j.1525-1497.2005.0243.x. PMID 16423108.
8. Turek FW, Gillette MU (November 2004). "Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists". Sleep Med. 5 (6): 523-32. doi:10.1016/j.sleep.2004.07.009. PMID 15511698.
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