Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of 8 Week Treatment of Rozerem 8 mg (QHS) in Sleep Disturbed, Mild to Moderately Severe Alzheimer's Disease Subjects
Brief Summary: The purpose of this study is to determine the efficacy of ramelteon, once daily (QD), in subjects with mild to moderate Alzheimer's Disease and sleep disturbance


Options:
A: Inclusion Criteria:

* age 65 years or older
* diagnosis of dementia
* a score ≥ 4 points on the Global Deterioration Scale (GDS; Reisberg et al., 1982), ranging from moderate to very severe cognitive decline.

Exclusion Criteria:

* high ocular sensitivity to light (photosensitivity)
* preexisting ocular abnormalities
* having any severe ocular disorder that did not allow them to open their eyes or that implied a very low visual acuity.
B: Inclusion Criteria

* Clinical diagnosis of dementia of the Alzheimer's type (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised) or probable Alzheimer's disease by National Institute of Neurological and Communicative Disorders and Stroke/the Alzheimer's Disease and Related
* Disorders Association criteria.
* Female subjects must be post-menopausal.
* Stable residence with no planned move during the entire investigation period.
* Residing in the same residence with a responsible spouse, family member, or a professional caregiver who is present during the night who would agree to assume the role of the principal caregiver for the duration of the protocol period.
* Able to ingest oral medication and participate in all scheduled evaluations.
* Clinical laboratory evaluations (including clinical chemistry, hematology, and urinalysis) within the reference range as tested by the designated laboratory unless the results are deemed not clinically significant by the investigator or sponsor.
* Treatment medications for any non-excluded medications or concurrent medical conditions are stable for 30 days prior to the screening visit and medication(s) can in the investigator's judgment, remain stable throughout the duration of the study.
* Mini-Mental State Examination score of 8 to 28, inclusive.
* History of greater than or equal to 2 sleep disorder behaviors, occurring at least once weekly over the two weeks before screening.
* Actigraphy evidence shows a nighttime total sleep time of less than 7 hours per night based on at least 4 out of 7 nights of complete actigraphy data collected over the single-blind, placebo run-in period.
* Habitual bedtime of between 8 PM and 12 AM.

Exclusion Criteria

* Non-ambulatory, wheel chair bound or confined to bed and is without a consistent caregiver who is present during the night who could function as the primary caregiver.
* Caregiver is deemed by the investigator to be unreliable to supervise the wearing of the actigraphy, to complete the sleep log, to administer medication at the proper time, to bring the subject to the scheduled visits or to answer questions regarding the subject's condition or medication use.
* Lacks a mobile upper extremity to which to attach an actigraphy.
* Currently participating or has participated in another clinical study within the past 30 days.
* Demonstrates an unwillingness to abstain from caffeine after 2:00 PM for the duration of the clinical trial participation.
* Demonstrates an unwillingness 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.
* Uses tobacco products or any other products during nightly awakenings that may interfere with the sleep wake cycle.
* History of drug abuse or tests positive for the presence of illicit drugs.
* Donated more than 400 mL of blood within the 90 days preceding the beginning of the study.
* Diastolic blood pressure greater than 95 mm Hg or a systolic pressure of greater than 160 mm Hg.
* Body mass index of greater than 36.
* Alanine transaminase level of greater than two times the upper limit of normal, active liver disease, jaundice or any clinically significant abnormal laboratory findings as determined by the investigator.
* History of a hypersensitivity or allergies to Ramelteon or melatonin.
* History of contraindications as noted in the Ramelteon label
* History of significant stroke or vascular dementia.
* History of severe renal dysfunction or disease.
* History of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study drug. (This criterion does not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.)
* Any clinically significant movement disorder including but not limited to: akinesia, periodic limb movement disorder, restless leg syndrome, epilepsy, uncontrolled Parkinson's disease, or severe benign prostatic hyperplasia, cardiac asthma, chronic obstructive pulmonary disease.
* Rapid eye movement behavior disorder or sleep apnea.
* Any pain syndrome affecting sleep.
* Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

  * Fluvoxamine
  * Melatonin
  * Rifampicin
C: Inclusion Criteria:

* \>= 55 Years old
* MMSE 14-26
* Prodromal Alzheimer's Disease (AD), AD or Mild Cognitive Impairment (MCI) due to AD
* Participation of a caregiver

Exclusion Criteria:

* Profound hearing or visual impairment
* Seizure Disorder
* Use of memantine (Namenda or Namzaric)
* Implantable devices (non-MR compatible)
D: Inclusion Criteria:

* 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.

Answer: B