Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase IIa Safety and Tolerability Study to Investigate the Effect on Sleep of 3 Doses of AZD5213 and Placebo in Patients With Mild Alzheimer's Disease and Mild Cognitive Impairment During 4 Weeks of Treatment, Placebo-Controlled
Brief Summary: This is a study where AZD5213 or placebo is given to patients with Mild Alzheimer's Disease or Mild Cognitive Impairment in a blinded and random assignment. The main study objective is to estimate the relationship of sleep duration versus dose after 4 weeks of treatment.


Options:
A: Inclusion Criteria:

* Patient and study partner to sign informed consent before initiation of any study-related procedures.
* Clinical diagnosis of Alzheimers (AD) or mild cognitive impairment (MCI) disease.
* Single caregiver for at least 6 months prior to Screening, capable of accompanying the patient on clinic visits as needed. The caregiver must either be living with or visiting the patient at least 10 hours per week, split over multiple (at least 2) days, for the duration of the study.
* Single study partner, for at least several months prior to Screening, capable of accompanying the patient on clinic visits as needed. The study partner must either be living with or visiting the patient at least 3 days per week for the duration of the study.
* A body mass index (BMI=weight/height2) of 18 kg/m2 to 32 kg/m2.

Exclusion Criteria:

* Significant neurological disease or dementia other than AD or MCI.
* Current episode or symptoms of major depressive disorder or other major psychiatric disorder.
* History of self-reported sleep duration of less than 4 hours per night or less than 4 hours average total sleep time per night during Baseline PSG assessment.
* History or present symptoms of a sleeping disorder such as sleep apnea.
* History of cancer in the last 5 years.
* Use of anti-AD drugs (including off-label drugs and herbal medications) with the exception of donepezil, memantine, and/or rivastigmine transdermal system, as monotherapy or in combination in the following conditions: treatment with donepezil (5 mg to 10 mg daily), memantine, and/or rivastigmine transdermal system or combination regimens for at least 3 months and a stable dose(s) for the last 2 months prior to randomization is allowed.
B: Inclusion Criteria:

* Diagnosis of probable Alzheimer's disease based on either a) the National Institute on Aging - Alzheimer's Association (NIA-AA) criteria or b) the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, (DSM-5) criteria for AD.
* Have sleep complaints that meet DSM-5 criteria for a diagnosis of insomnia (e.g., difficulty initiating or maintaining sleep, and/or early morning awakenings with inability to return to sleep for at least 3 nights per week for ≥ the past 3 months prior to study start, despite adequate opportunity for sleep) based on the investigator's judgment and by the participant's sleep history, as assessed by the sleep items on the Insomnia Diagnostic Interview and Sleep History assessments.
* Be willing to stay overnight in a sleep laboratory and must be willing to stay in bed for at least 8 hours for PSG testing
* Regular bedtime is between 8 pm and 1 am and is willing to maintain it for the duration of the trial
* Be able and willing to wear an activity/sleep watch on the wrist throughout the day and night
* Based on the investigator's judgment the participant should: a) be able to speak, read, and understand the language of the trial staff and the informed consent form; b) possess the ability to respond verbally to questions, follow instructions, and complete study assessments; c) be able to adhere to dose and visit schedules.
* Have a reliable and competent trial partner (e.g., spouse, family member, or other caregiver) who:
* a) Signs their own informed consent, after the trial has been explained to them, and before Screening assessments;
* b) Is not diagnosed with dementia;
* c) Resides with the participant overnight and has a close relationship with the participant (defined as daily face-to-face contact, at least 15 waking hours a week for at least 3 months prior to Visit 1);
* d) Accompanies the participant to and from trial visits and stays overnight at the sleep laboratory for the 3 PSG visits;
* e) Assumes responsibility for trial medication procedures (e.g., witnessing and/or helping to administer trial medication, assessing compliance), for completion of the sleep e-diary each morning, and oversight of the activity/sleep watch worn throughout the trial;
* f) Answers questions regarding the trial partner's sleep quality and trial partner's distress related to the subject's behaviors.
* If female, not of childbearing potential as indicated by one of the following: has reached natural menopause, defined as:
* a) ≥45 years of age with either: ≥12 months of spontaneous amenorrhea OR ≥6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels \> 40 IU/L as determined by the central laboratory
* b) has had a hysterectomy;
* c) has had bilateral tubal ligation; or
* d) has had a bilateral oophorectomy (with or without a hysterectomy) and greater than 6 weeks have passed since the surgery
* Be willing to provide a blood sample for Apolipoprotein E (APOE) genotyping

Exclusion Criteria:

* Apnea Hypopnea Index (AHI) score \> 30 or Periodic Leg Movements with Arousal per hour of Sleep (PLMA) \> 30.
* Resides in a nursing home (or similar institutional facility); assisted-living facilities are not excluded if full-time nursing care is not required.
* Has a Modified Hachinski Ischemia Scale (MHIS) Score \> 4 at Screening (i.e., evidence of vascular dementia)
* Has a known history of recent (or past) stroke that in the investigator's opinion confounds the diagnosis of either AD or insomnia
* Has evidence of a clinically relevant neurological disorder other than the disease being studied (i.e., probable AD) at Screening, including but not limited to: vascular dementia, parkinsonism, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, progressive supranuclear palsy, neurosyphilis, dementia with Lewy bodies, other types of dementia, mental retardation, hypoxic cerebral damage, cognitive impairment due to other disorders, or history of head trauma with loss of consciousness that either led to persistent cognitive deficits or in the opinion of the investigator confounds the diagnosis of either AD or insomnia.
* Has a history of seizures or epilepsy within the last 5 years before study start
* Has a history or diagnosis of any of the following conditions, in the opinion of the investigator:
* Narcolepsy
* Cataplexy (familial or idiopathic)
* Circadian Rhythm Sleep Disorder
* Parasomnia including nightmare disorder, sleep terror disorder, sleepwalking disorder
* Rapid eye movement (REM) behavior disorder
* Significant degree of sleep-related Breathing Disorder (i.e., AHI \>30, and/or use of Continuous Positive Airway Pressure \[CPAP\] or Bilevel Positive Airway Pressure \[BIPAP\])
* Periodic Limb Movement Disorder
* Restless Legs Syndrome
* Primary Hypersomnia
* Excessive Daytime Sleepiness (EDS) characterized by uncharacteristic chronic and persistent sleepiness throughout the day
* Has a clinically significant movement disorder, such as akinesia, that would affect the activity/sleep watch differentiation of sleep and wakefulness
* In the opinion of the investigator, has difficulty sleeping primarily due to a confounding medical condition. NOTE: "Medical Conditions" may include chronic pain syndromes, chronic migraine, cardiac disease, nocturia (\> 3 times/night), asthma, gastroesophageal reflux disease (GERD), or hot flashes.
* Has evidence of a current episode of major depression based on investigator's judgment. Major depression in remission is not exclusionary.
* Has any of the following based on clinician interview and DSM-5 criteria:
* Lifetime history of bipolar disorder, a primary psychotic disorder, or posttraumatic stress disorder; or,
* A psychiatric condition requiring treatment with a prohibited medication; or,
* Other psychiatric condition that, in the investigator's opinion, would interfere with the subject's ability to participate in the study.
* Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator. Subjects must be excluded if they report suicidal ideation with intent, with or without a plan or method in the past 2 months or suicidal behavior in the past 6 months.
* Has a history of alcoholism or drug dependency/abuse within the last 5 years of study start
* Has a recent history (within the 6 months prior to Screening) of regular consumption (3 or more days per week) of either:
* More than 2 alcoholic beverages per day or alcohol consumption within 3 hours prior to bedtime
* More than \> 600 mg caffeine a day (e.g., 4 standard 8-ounce cups of brewed coffee, or consumes caffeine after 4pm (16:00)
* Consumes the equivalent of \>15 cigarettes a day and the investigator confirms that the participant's insomnia is in part the result of tobacco consumption (e.g., participants unable to refrain from smoking during the night, participants who interrupt sleep to smoke or use tobacco products, or participants who require a cigarette within 30 minutes of waking in the morning).
* Has a history of excessive daytime napping (defined as more than 3 hours a day for more than 3 days of the week based on trial partner estimates, on average for the past 4 weeks).
* Has a recent or ongoing, uncontrolled, clinically significant medical condition or major surgery where participation in the trial would pose a significant medical risk to the subject within 3 months of study start, such as: conditions including but not limited to diabetes, hypertension, Human Immunodeficiency Virus (HIV) or other relevant infections, thyroid or endocrine disease, Chronic Obstructive Pulmonary Disease (COPD), delirium, congestive heart failure, angina, cardiac or gastrointestinal disease, or renal disease requiring dialysis. Note: controlled co-morbid conditions (including diabetes, hypertension, heart disease, etc.) are not exclusionary if stable within 3 months of the study start. All concomitant medications, supplements, or other substances must be kept as stable as medically possible during the trial. Urinary tract infections at study start are not exclusionary if adequately treated.
* Major surgery including not limited to abdominal, thoracic, cardiac or orthopedic surgery, or any procedure requiring general anesthesia
* Has a history of hepatitis or liver disease that, in the opinion of the investigator, has been active within the 6 months prior to study start.
* Has a known allergy or hypersensitivity to suvorexant or to any of the formulation components
* Has a history of hypersensitivity or idiosyncratic reaction to more than 3 chemical classes of drugs, including prescriptions and over-the-counter medications.
* Has donated blood products or has had phlebotomy of \>300 mL within 8 weeks of study start, or intends to donate or receive blood products during participation in the study.
* History of malignancy within the 5 years prior to study start, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized prostate cancer, who has undergone potentially curative therapy with no evidence of recurrence for \>=3 year post-therapy, and who is deemed at low risk for recurrence by her/his treating physician.
* Is pregnant, is attempting to become pregnant, or is nursing children
* Has a Body Mass Index (BMI) \> 40 kg/m\^2
* Is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent
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: A