There is emerging evidence connecting poor sleep quality and Alzheimer’s disease. The Brain Science Institute states that patients with Alzheimer’s disease exhibit changes in their sleep patterns, including fragmentation of their sleep and reduced sleep at night.1 The researchers for this study noted that internal melatonin levels are already reduced at preclinical Alzheimer’s disease stages, and they investigated whether replenishing the missing melatonin hormone would be beneficial in Alzheimer’s disease. Also, they wanted to evaluate whether any such effects would be related to the presence of a sleep disorder in Alzheimer’s disease patients.2
The study demonstrated that prolonged-release melatonin has positive effects on cognitive functioning and sleep maintenance in Alzheimer’s disease patients, particularly in patients who also have insomnia. Overall, patients in the prolonged-release melatonin treatment group had significantly better cognitive performance at 24 weeks than those who received the placebo. Sleep efficiency was also better with the prolonged-release melatonin treatment group.
This research study was performed on recruited outpatients attending five centers, one in the UK (n=35 patients) and four in the USA (n=45 patients). The Alzheimer’s disease Assessment Scale–Cognition, Instrumental Activities of Daily Living, Mini–Mental State Examination, sleep (assessed by the Pittsburgh Sleep Quality Index and a daily sleep diary), and safety parameters were measured for each patient. The study population included 80 male and female outpatients (ages 50–85) diagnosed with mild to moderate Alzheimer’s disease and a Mini–Mental State Examination score of ≥15. Computed tomography, positron emission tomography, or magnetic resonance imaging scans were conducted to ensure patients had no evidence of disease to account for dementia. Following diagnosis, all patients underwent a 2-week placebo period. Then the patients were randomized into a group receiving treatment with prolonged-release melatonin (Circadin® 2 mg) or receiving a placebo for 24 weeks, followed by a 2-week placebo period to conclude the study. The tablets the patients in the placebo group received were identical in appearance, taste, and odor to the treatment tablets, to try and prevent bias. The placebo or treatment study medications were administered one tablet per day, taken orally 1–2 hours before bedtime, preferably at 9 pm and after dinner. Also, all the patients were instructed to spend 2 hours a day in outdoor daylight.
Seven patients were excluded from the study before randomization, due to noncompliance. Thus, 39 patients were randomized into the treatment group and 34 into the placebo group, but only 60 patients (82.2%) completed the study (31 treatment and 29 placebo). Over 70 percent of the patients in the study did not have insomnia. Only 13 patients were in the insomnia comorbid subpopulation (7 in the prolonged-release melatonin treatment group and 6 in the placebo group).
The average Alzheimer’s disease Assessment Scale–Cognition score did not differ between the groups. There were no statistically significant differences in demographics or baseline characteristics between the treatment and placebo groups. After 24 weeks of treatment, there were no significant differences in treatment effects in the Pittsburgh Sleep Quality Index (PSQI) global score between the groups. The PSQI global score significantly decreased (improved) compared with baseline in the treatment group but not in the placebo group. Sleep efficiency was also better with the prolonged-release melatonin treatment group. When the patients were divided into sub-groups based on their PSQI scores, the comorbid insomnia (PSQI ≥6) subgroup receiving the prolonged-release melatonin treatment (n=7) had significant and clinically meaningful effects versus the placebo (n=6), in mean Instrumental Activities of Daily Living, Mini–Mental State Examination score, and sleep efficiency. Median Alzheimer’s disease Assessment Scale–Cognition values were significantly better with prolonged-release melatonin treatment, and the differences were more significant at longer treatment duration. Notably, the prolonged-release melatonin was well tolerated, similarly to the toleration of the placebo. The researchers concluded that prolonged-release melatonin has positive effects on cognitive functioning and sleep maintenance in Alzheimer’s disease patients compared with placebo, particularly in those patients who also have insomnia.
- John Hopkins Medicine: The Brain Science Institute. The Relationship Between Sleep and Alzheimer’s Disease. http://www.brainscienceinstitute.org/brain_talk/the_relationship_between_sleep_and_alzheimers_disease. Accessed on September 6, 2016.
- Wade AG, Farmer M, Harari G. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer’s disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clinical Interventions in Aging. 2014;9:947-61. .