Table 2.

Specific outcome measures and instruments

Primary outcome measure • API Cognitive Composite Test (derived from elements of the following) ○ Word List: Recall [35], [36], [37] ○ Multilingual Naming Test [38] ○ Consortium to Establish a Registry for Alzheimer's Disease Constructional Praxis Test [36] ○ Mini–Mental State Examination (for Orientation to Time) [39] ○ Ravens Progressive Matrices [40] Secondary outcome measures • Clinical ○ Time to progression to mild cognitive impairment or dementia due to Alzheimer's disease [33] ○ Clinical Dementia Rating (global score and sum of boxes) [41] • Biomarkers ○ Cerebral fibrillar amyloid burden measured by florbetapir positron emission tomography (PET) ○ Regional cerebral metabolic rate of glucose using fluorodeoxyglucose (FDG)-PET ○ Volumetric magnetic resonance imaging ○ Cerebrospinal fluid (CSF) levels of β amyloid, p-tau, and total tau • Safety ○ Safety laboratories ○ Electrocardiogram ○ Magnetic resonance imaging ○ Suicidality Assessment (Copyright Pfizer Inc. and Janssen Alzheimer Immunotherapy; used with permission) ○ Physical and neurological examination ○ Vital signs • Pharmacokinetic/pharmacodynamic measures (PK/PD) ○ PK: CSF and serum crenezumab concentrations at protocol-specified time points (trough serum concentrations are assessed at steady state) ○ PD: plasma Aβ1–40 and Aβ1–42 concentrations Exploratory outcome measures • Clinical ○ Trail Making Test [42], Mini–Mental State Examination [39] ○ Repeatable Battery for the Assessment of Neuropsychological Status [43] ○ Free and Cued Selective Reminding Task (FCSRT) [44] ○ Scores of each of the components of the API Composite Cognitive Battery ○ Neuropsychiatric Inventory [45], [46] ○ Geriatric Depression Scale [47] ○ Functional Assessment Staging of Alzheimer's Disease [48] ○ Subjective Memory Checklist [16] • Fluid biomarkers ○ Cerebrospinal fluid levels of other Aβ species ○ Changes in other blood and cerebral spinal fluid measures • Imaging biomarkers ○ Analysis of regions of interest not selected in secondary end point • Other ○ Changes in primary, secondary, and exploratory outcomes in carriers and noncarriers as function of APOE and genetic variations

Abbreviations: API, Alzheimer's Prevention Initiative; Aβ, amyloid β; APOE, apolipoprotein E.