Multiple Dose Trial of MK-4334 in Participants With Alzheimer's Clinical Syndrome (MK-4334-005)

Participants with MCI

• Have a history of subjective memory decline with gradual onset and slow progression for at least one year before screening.
• Have general cognitive function and activities of daily living sufficiently intact, based on clinical assessment, so as not to meet criteria for mild AD dementia based on National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
• Have a Mini Mental State Exam-2 (MMSE-2) score ≥24.
• Have a Clinical Dementia Rating (CDR) scale score of 0.5, including a memory subscale score ≥ 0.5.

Participants with AD

• Have a history of cognitive and functional decline with gradual onset and slow progression for at least one year before screening.
• Meet the criteria for a diagnosis of probable AD based on NINCDS-ADRDA criteria.
• Have a MMSE-2 score ≥ 12 to ≤ 24 at screening.
• Have a CDR score of 1 to 2.

All Participants

• Have a Rosen-Modified Hachinski score ≤ 4.
• Be on a stable dose of donepezil 10 mg PO daily for symptomatic treatment of Alzheimer's clinical syndrome. The dose must be stable for ≥2 months prior to screening.
• Be in good health based on medical history, physical examination, vital sign (VS) measurements and electrocardiograms (ECGs) performed prior to randomization.
• Have a Body Mass Index (BMI) ≤ 35 kg/m\^2.
• If female, is a woman of non-childbearing potential (WONCBP).
• If male, must agree to either remain abstinent or use contraception during the intervention period and for ≥28 days after the last dose of study intervention.
• Have acceptable venous access.

Exclusion Criteria:

• 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.
• Has a history of uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases.
• Has evidence of a clinically relevant or unstable psychiatric disorder, based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, including schizophrenia or other psychotic disorder, bipolar disorder, or delirium, at the time of prestudy (screening) visit, or has a history of clinically significant psychiatric disorder of the last 5 years.
• Has a history of cancer (malignancy), except for: 1.) adequately-treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; 2.) Other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study.
• Participant has an estimated creatinine clearance (CrCl) ≤55 mL/min based on the Modification of Diet in Renal Disease (MDRD).
• Has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e., systemic allergic reaction) to prescription or non-prescription drugs or food.
• Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV).
• Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
• Is unable to refrain from or anticipates the use of strong or moderate inhibitors or inducers of Cytochrome P450 (CYP) 3A4 (CYP3A4) and CYP2C19 beginning approximately 28 days prior to administration of the initial dose of study drug, throughout the study, and until the post-trial visit.
• Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit.
• Has a rate-corrected QT (QTc) interval ≥470 msec (for males) or ≥480 msec (for females).
• Is a smoker and/or has used nicotine or nicotine-containing products (e.g., nicotine patch and electronic cigarette) within 3 months of screening.
• Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day.
• Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
• Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 2 years. Participants must have a negative urine drug screen prior to randomization.