Study of Melatonin: Sleep Problems in Alzheimer's Disease

• Patients must meet NINCDS-ADRDA criteria for probable Alzheimer's disease (AD). Patients must have disrupted sleep, documented by clinical history and by 1 to 2 weeks of recording using wrist activity monitors.
• A diagnosis of probable AD.
• MMSE score 0-26.
• Hachinski Ischemia Scale score less than or equal to 4.
• A 2-week history of two or more sleep disorder behaviors, occurring at least once weekly, as reported by the caregiver on the Sleep Disorder Inventory.
• CT or MRI since the onset of memory problems showing no more than one lacunar infarct in a non-strategic area and no clinical events suggestive of stroke or other intracranial disease since the CT or MRI.
• Physically acceptable for study as confirmed by medical history and exam, clinical laboratory results, and EKG.
• Actigraph evidence of a mean nocturnal sleep time of less than 7 hours per night (at least 5 nights of complete actigraph data must be collected over a single week.
• Stable home situation with no planned move during the 13-week investigational period.
• Residing with responsible spouse, family member, or professional caregiver who is present during the night and will agree to assume the role of the principal caregiver for the 13-week protocol, including arranging transport for the patient to and from the investigators' clinic, answering questions regarding the patient's condition, and assuming responsibility for medication and actigraph procedures.
• Ability to ingest oral medication and participate in all scheduled evaluations.
• Six grades of education or work history sufficient to exclude mental retardation.
• 55 years of age or older.
• Hamilton Depression Rating Scale score of 15 or less.
• Stable medication (dose and type) for non-excluded concurrent medical conditions for 4 weeks prior to the screening visit.

Exclusion Criteria:

• Sleep disturbance is acute (within the last 2 weeks).
• Sleep disturbance is associated with an acute illness with delirium.
• Clinically significant movement disorder that would interfere with the actigraph readings.
• Not having a mobile upper extremity to which to attach an actigraph.
• Severe agitation.
• Pain syndrome affecting sleep.
• Unstable medical condition.
• Use of investigational or unapproved medications within 4 weeks of the screening visit.
• Patient unwilling to maintain caffeine abstinence after 2:00 pm for the duration of the protocol.
• Patient unwilling to comply with the maximum limit of two alcoholic drinks per day, and only one alcoholic drink after 6:00 pm for the duration of the protocol.
• Use of melatonin within 2 weeks of screening visit.
• Clinically significant abnormal laboratory findings that have not been approved by the Project Director.
• Residing in a facility without a consistent caregiver present during the night who can function as the primary informant.
• Caregiver deemed too unreliable to supervise the wearing of the actigraph, to maintain the sleep diary, or to bring the patient to the scheduled visits.
• Autoimmune disease, such as rheumatoid arthritis and polymyalgia rheumatica.