A Phase 2b/3 Randomized Double-blind Placebo-Controlled Parallel Group Multicenter Study Investigating the Efficacy and Safety of JNJ-54861911 in Subjects who are Asymptomatic At Risk for Developing Alzheimer's Dementia

Inclusion Criteria
Subjects must be a man or woman 60 to 85 years of age, inclusive, at the time of informed consent. Subjects 60 to 64 years of age must also have 1 of the following 3 conditions:
a positive family history for dementia (minimum of 1 first degree relative)
a previously known APOE E4 genotype
a previously known biomarker status demonstrating elevated amyloid accumulation in CSF or PET
Subject must have a global CDR score of 0 at Screening
Subjects must be able to read and write and must have adequate hearing and visual acuity to complete the psychometric tests. The legally acceptable representative must also be able to read and write
Subjects must have evidence of elevated amyloid accumulation by means of either:
low CSF ABI-42 levels at Screening
a positive amyloid PET scan at Screening
Subjects must be otherwise healthy for their age group or medically stable with or without medication on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at Screening or at Baseline
Subject must be otherwise healthy or medically stable on the basis of clinical laboratory tests performed at Screening
Subjects must have a reliable informant (relative, partner, or friend) The informant must be willing to participate as a source of information and must have at least weekly contact with the subject (contact can be in-person, via telephone, or other audio/visual communication). The informant must have sufficient contact such that the investigator believes he/she will provide consistent, accurate, and meaningful information on clinical scales (eg CDR and CFI)
Subject must be able to swallow drug as a whole and to be compliant with self-administration of medication
Subject must reside at a permanent address other than a nursing facility
Exclusion Criteria
Subject is receiving an acetylcholinesterase (AChE) inhibitor and/or memantine at any time during Screening or Day 1 predose
Subject has evidence of any brain disease other than potential very early stages of AD or typical age-related changes
Subject has any other abnormality that could case a possible cognitive deficit
Subject has any contraindications for MRI
Subject has met criteria for dementia or has a brain disorder that can cause dementia
Subject has evidence of familial autosomal dominant AD
Subject has a history of or current thyroid disease or thyroid dysfunction, which is currently uncontrolled, unevaluated, or untreated
Subject has a vitamin B12 or folic acid deficiency
Subject has chromosome 21 trisomy (Down syndrome)
Subject has a history within the past 2 years or current diagnosis of significant psychiatric illness; or the subject has a current diagnosis or history of schizophrenia or bipolar disorder
Subject has a relevant history of or current neurological disease other than preclinical AD, which may make interpretation of possible new neurological signs or symptoms difficult
Subject has had a history within the last 5 years of a serious infectious disease affecting the brain or head trauma resulting in protracted loss of consciousness
Subject has a history of epilepsy. Subject has a history of fits or unexplained black-outs other than vasovagal syncope within 10 years before screening
Subject has a hypopigmentation abnormality of the skin such as vitiligo, other than small localized findings, at screening dermatological test
Subject has any amyloid-related imaging abnormalities - edema or effusion (ARIA-E) at screening
Subject has a clinically significant abnormal physical or neurological examination or vital signs at screening or baseline, which in the opinion of the investigator is not appropriate and reasonable for the population under study
Subject has a history of moderate or severe hepatic impairment or severe renal insufficiency unless completely resolved for more than a year. Subject has clinically significant ongoing hepatic, renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric, or metabolic conditions
Subject has a history of malignancy within 5 years before screening
Subject has current, clinical relevant anemia
Subject has a history of positive tests for hepatitis B surface antigen or hepatitis C virus antibody, or other clinically active liver disease, or tests, or tests positive for HBsAg or anti-hepatitis C virus at screening
Subject has a history of a positive test for human immunodeficiency virus (HIV) antibody, or tests positive for HIV at screening
Subject has known allergies, hypersensitivity, or intolerance to JNJ-54861911 or its excipients