A Study to Evaluate the Efficacy and Safety of Gantenerumab in Participants at Risk for or at the Earliest Stages of Alzheimer's Disease (AD)

Exclusion Criteria

• •Any evidence of an underlying neurological or neurodegenerative condition that may lead to cognitive impairment other than AD.
• •Clinical diagnosis of mild cognitive impairment (MCI), prodromal AD, or any form of dementia.
• •History or presence of intracranial or intracerebral vascular malformations, aneurysm, subarachnoid hemorrhage, or intracerebral macrohemorrhage.
• •History or presence of posterior reversible encephalopathy syndrome.
• •History of ischemic stroke with clinical symptoms or an acute event that is consistent with a transient ischemic attack within 12 months of screening.
• •History of severe, clinically significant (i.e., resulting in persistent neurologic deficit or structural brain damage) central nervous system (CNS) trauma (e.g., cerebral contusion).
• •History or presence of intracranial mass lesion (e.g., glioma, meningioma) that could potentially impair cognition or lead to progressive neurological deficits.
• •Infections that may affect brain function or a history of infections that resulted in neurologic sequelae \[e.g., human immunodeficiency virus (HIV), syphilis, neuroborreliosis, and viral or bacterial meningitis and encephalitis\].
• •History of major depression, schizophrenia, schizoaffective disorder, or bipolar disorder.
• •At risk for suicide.
• •History of alcohol and/or substance abuse or dependence.
• •History or presence of clinically significant systemic vascular disease, atrial fibrillation or heart failure.
• •Within the last year, experienced unstable or clinically significant cardiovascular disease (e.g., myocardial infarction).
• •Uncontrolled hypertension.
• •Chronic kidney disease, indicated by creatinine clearance \<30 mL/min.
• •Confirmed and unexplained impaired hepatic function.
• •History of, or are known to currently have an HIV infection, or hepatitis B or hepatitis C virus infection that has not been adequately treated.
• •History or presence of systemic autoimmune disorders that may lead to progressive neurological impairment with associated cognitive deficits.
• •Systemic immunosuppression or immunomodulation due to the continuing effects of immunosuppressant or immunomodulating medications.
• •Current COVID-19 infection.
• •Evidence of folic acid or vitamin B-12 deficiency.
• •Any passive immunotherapy (Ig) or other long-acting biologic agent to prevent or postpone cognitive decline within 1 year of screening.
• •Any other investigational treatment within 5 half-lives or 6 months (whichever is longer) prior to screening.
• •Typical/Atypical anti-psychotic medications or neuroleptic medications.
• •Anticoagulation medications within 3 months of screening with no plans to initiate any prior to randomization.
• •Any previous treatment with cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists are exclusionary at screening.
• •Pregnant or breastfeeding, or intending to become pregnant during the study or within 17 weeks after the final dose of gantenerumab.
• •Impaired coagulation.
• •Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins, including gantenerumab and gantenerumab excipients.
• •Participants who reside in a skilled nursing facility such as a convalescent home or long-term care facility.
• •Participants who require residence in such facilities during the study may continue in the study and be followed for efficacy and safety, provided that they have a study partner who meets the study partner requirements.