Double Blind Study of Melatonin Effects on the Sleep-wake Rhythm, Cognitive and Non-cognitive Functions in Alzheimer Type Dementia

Previously, we reported that morning bright light therapy improved sleep time and cognitive function in Alzheimer type of dementia. We conducted a double blind study to examine the effects of melatonin on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type of dementia. The subjects were 9 persons given a placebo（PLA）,
and 11 given melatonin（ 3 mg）（MLT). The mean age was 79.2±6.4（17 females and 3 males).The drugs were given at 20:30 each day for 4 weeks. We checked sleep time and activity by Actigraph through one week before and the 4 th week after drug administration. Cognitive and non-cognitive functions were evaluated with the clinical dementia rating scale（CDR）, and Mini Mental State Examination（MMSE), and the Alzheimer’s Disease Assessment Scale（ADAS). We successfully recorded Actigraph data from 18 patients（PLA 8, MLT 10). The mean sleep time change ratio and SD of the administration of PLA in the night was－0.2±13.7％, and MLT was 33.2±37.6％. The mean activity counts and SD of the administration of PLA in the night was 29.8±77.0％; in MLT it was－44.9±21.9％. Melatonin significantly prolonged the sleep time（p＝0.017）and decreased activity（p＝0.014）in the night（21: 00～6: 00）in the MLT group, although no significant difference in sleep time or activity in the daytime（6: 00～21: 00）was recognized between the two groups. In comparison with ADAS cognition score changes, the mean change and SD in the PLA was 0.3±3.7; in MLT it was－4.3±3.6 points. In comparison with ADAS non-cognition score, the mean change and SD in the PLA group was －0.8±1.0, in the MLT group it was－4.1±2.2 points. There were also significant differences between the PLA and the MLT groups in the comparison with the score improvement of ADAS cognition（p＝0.017）and non-cognition（p＝0.002）, otherwise there was no significant
difference in improvement of MMSE between both groups. Melatonin administration had effect to improve sleep time and night activity, but no significant effect to improve daytime naps and activity. Although melatonin administration might has less strong effect on circadian rhythm than morning bright light therapy we previously reported, cognitive and non-cognitive functions were improved. Melatonin seemed to be useful for care of the Alzheimer type of dementia patients.