Study of Melatonin: Sleep Problems in Alzheimer's Disease

In Alzheimer's disease , sleep disruption is one of the most common behavioral problems, occurring in 45 percent of patients. These nocturnal awakenings and agitation lead to considerable burden for caregivers and frequently lead families to the decision of nursing home placement. The proposed study is a randomized, double blind, parallel group, placebo controlled, clinical trial. Placebo will be compared with two doses of melatonin: a 2.5 mg, slow- release preparation and a 10 mg immediate release preparation. One hundred and fifty community-residing AD patients with disrupted sleep will be recruited. Included subjects will meet NINCDS-ADRDA criteria for probable AD. Prior to study entry, disrupted sleep will be documented by clinical history and by 1 to 2 weeks of recording using wrist activity monitors. The treatment period will last 8 weeks. Rest/activity patterns will be recorded by wrist activity monitors. The primary outcome measure will be the change in nocturnal sleep time from baseline to the end of the treatment phase.

Other outcomes also will be examined, including the time awake after sleep onset, sleep latency, sleep efficiency, daytime agitation, and changes in cognition. The relative effectiveness of high and low dose melatonin will be assessed. Adverse events and side effects will be compared by treatment. This study should provide the data necessary to determine whether melatonin is a safe and effective treatment for disrupted sleep associated with AD.