AHEAD 3-45 Study: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid

Inclusion criteria:

Participants must meet all of the following criteria to be included in this study:

1. Male or female, age 55 to 80 years inclusive at the time of informed consent, with aplasma biomarker result that is predictive of intermediate or elevated brain amyloidat Screening or known before Screening to have elevated or intermediate amyloidaccording to previous PET, cerebrospinal fluid (CSF), or plasma testing

• Those 55 to 64 must have 1 of the following additional risk factors, given therelatively low rates of amyloid positivity less than (<) 65 years, before screening:

• First degree relative diagnosed with dementia onset before age 75, or

• Known to possess at least 1 apolipoprotein E4 variant (APOE4) allele, or

• Known before screening to have elevated brain amyloid according to previousplasma biomarker results, PET imaging, or CSF testing

2. Global Clinical Dementia Rating (CDR) score of 0 at screening

3. Mini Mental State Examination score greater than or equal to (>=) 27 (witheducational adjustments) at screening.

4. Wechsler Memory Scale-Revised Logical Memory subscale II (WMS-R LM II) score atscreening of >=6

5. A45 Trial: Elevated brain amyloid pathology by amyloid PET: defined as approximatelygreater than (>) 40 Centiloids on screening scan A3 Trial: Intermediate levels ofbrain amyloid pathology by amyloid PET: defined as approximately 20 to 40 Centiloidson screening scan

6. Has a study partner that is willing to participate as a source of information andhas approximately weekly contact with the participant (contact can be in-person, viatelephone or electronic communication). The study partner must have sufficientcontact such that the investigator feels the study partner can provide meaningfulinformation about the participant's daily function

7. Provide written (or electronic, if allowed per country-specific regulations)informed consent

8. Willing and able to comply with all aspects of the protocol

For extension phase :

1. Completed the Core Study, or meet the following progression criteria during the CoreStudy:

• Two consecutive CDR visits with Global Scores > zero when measured at least 6months apart within the Core Study

• The principal investigator's confirmation that the participant has clinicallydeclined consistent progression to EAD

2. Must continue to have a study partner who is willing and able to provide follow-upinformation on the participant throughout the course of the Extension Phase. Thestudy partner must provide separate written informed consent for the ExtensionPhase. Study partners must continue to have sufficient contact such that theinvestigator feels the study partner can provide meaningful information about theparticipant's daily functions

3. Provide written informed consent for the Extension Phase. If a participant lackscapacity to consent in the investigator's opinion, the participant's assent shouldbe obtained, if required and in accordance with local laws, regulations, andcustoms, plus the written informed consent of a legal representative (capacity toconsent and the definition of a legal representative should be determined inaccordance with applicable local laws and regulations). In countries where locallaws, regulations, and customs do not permit participants who lack capacity toconsent to participate in this study (example, Spain), they will not be enrolled

4. Willing and able to comply with all aspects of the protocol

Exclusion criteria:

Participants who meet any of the following criteria will be excluded from this study:

1. Females who are breastfeeding or pregnant at screening or baseline

2. Females of childbearing potential who:

• Within 28 days before study entry, did not use a highly effective method ofcontraception For sites outside of Europe, it is permissible that if a highlyeffective method of contraception is not appropriate or acceptable to theparticipant, then the participant must agree to use a medically acceptable method ofcontraception

3. History of transient ischemic attacks (TIA), stroke, or seizures within 12 months ofscreening

4. Current or history within the past 2 years of psychiatric diagnosis or symptomsthat, in the opinion of the investigator, could interfere with study procedures

5. Contraindications to 3 Tesla magnetic resonance imaging (MRI) scanning, includingcardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in-skull andcardiac devices other than those approved as safe for use in MRI scanners), orexhibit other significant pathological findings on brain MRI at Screening

6. Hypersensitivity to any monoclonal antibody treatment

7. Any immunological disease which is not adequately controlled, or which requirestreatment with immunoglobulins, systemic monoclonal antibodies (or derivatives ofmonoclonal antibodies), systemic immunosuppressants, or plasmapheresis during thestudy

8. Bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5) at screening

9. Results of laboratory tests conducted during screening that are outside thefollowing limits:

• Thyroid stimulating hormone (TSH) above normal range

• Abnormally low (below lower limit of normal [LLN]) serum vitamin B12 levels forthe testing laboratory (if participant is taking vitamin B12 injections, levelshould be at or above the LLN for the testing laboratory). A low vitamin B12 isexclusionary, unless the required follow-up labs (homocysteine andmethylmalonic acid [MMA]) indicate that it is not physiologically significant

10. Known to be human immunodeficiency virus (HIV) positive

11. Any other clinically significant abnormalities that in the opinion of theinvestigator require further investigation or treatment or may interfere with studyprocedures or safety

12. Malignant neoplasms within 3 years of screening (except for basal or squamous cellcarcinoma in situ of the skin, or localized prostate cancer in male participantswith treatment cycles completed at least 6 months before screening). Participantswho had malignant neoplasms but who have had at least 3 years of documenteduninterrupted remission before screening need not be excluded

13. Answer "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideationType 4 or 5, or any suicidal behavior assessment within 6 months before screening,at screening, or at baseline, or has been hospitalized or treated for suicidalbehavior in the past 5 years before screening

14. Known or suspected history of drug or alcohol abuse or dependence within 2 yearsbefore screening or a positive urine drug test at screening. Participants who testpositive for benzodiazepines, opioids, or tetrahydrocannabinol (THC) in urine drugtesting need not be excluded unless in the clinical opinion of the investigator thisis due to potential drug abuse

15. Taking prohibited medications

16. Participation in a clinical study involving:

• Any anti-amyloid plaque lowering immunotherapy (example, therapeutic monoclonalantibody or active anti-amyloid vaccine) at any time, unless it can bedocumented that the participant was randomized to placebo or never receivedstudy drug

• Any immunoglobulin therapy, or vaccine within 6 months before Screening, unlessit can be documented that the participant was randomized to placebo or neverreceived study drug

• Lecanemab

• Any new chemical entities or investigational drug for AD within 6 months beforerandomization unless it can be documented that the participant received onlyplacebo

• Any other investigational medication or device study in the 8 weeks or 5half-lives (whichever is longer) of the medication before randomization unlessit can be documented that the participant was in a placebo treatment arm

17. Planned surgery during the pre-randomization phase or within 3 months ofrandomization, which requires general anesthesia

For extension phase:

1. Discontinued from the Core Study or from study treatment

2. Under study drug interruption due to ARIA or other AE at the time of transition tothe extension phase