biostudies-literatureCaputo ANIA NIH HHS45https://www.ebi.ac.uk/biostudies/studies/S-EPMC9987044biostudies-literatureUnknown15(1)<h4>Background</h4>There is a critical need for novel primary endpoints designed to detect early and subtle changes in cognition in clinical trials targeting the asymptomatic (preclinical) phase of Alzheimer's disease (AD). The Alzheimer's Prevention Initiative (API) Generation Program, conducted in cognitively unimpaired individuals at risk of developing AD (e.g., enriched by the apolipoprotein E (APOE) genotype), used a novel dual primary endpoints approach, whereby demonstration of treatment effect in one of the two endpoints is sufficient for trial success. The two primary endpoints were (1) time to event (TTE)-with an event defined as a diagnosis of mild cognitive impairment (MCI) due to AD and/or dementia due to AD-and (2) change from baseline to month 60 in the API Preclinical CompoAlzheimer's research & therapyRationale for the selection of dual primary endpoints in prevention studies of cognitively unimpaired individuals at genetic risk for developing symptoms of Alzheimer's disease.PMC9987044R01 AG015819P30 AG062677P30 AG066514P30 AG066515P30 AG072980P30 AG066518P30 AG066519P30 AG062715P20 AG068053P30 AG066462P30 AG072975P30 AG072931P30 AG072976P20 AG068077P30 AG072977P30 AG019610P30 AG066444P30 AG072972R01 AG022018P30 AG072973P30 AG066468P30 AG072978P30 AG072979R01 AG079280P30 AG072958P30 AG072959P30 AG062421UF1 AG046150P30 AG062422P30 AG010161P30 AG066546P30 AG066506P30 AG066507P30 AG062429P30 AG066508P30 AG066509P30 AG066530P20 AG068082P30 AG066511P30 AG066512U24 AG072122U01 AG024904P20 AG068024R01 AG017917P30 AG072946P30 AG072947National Alzheimer’s Coordinating CenterCoello NLopez CLRiviere MELangbaum JBRacine APaule IRyan JMGraf ACaputo ATariot PNAlzheimer’s Disease Neuroimaging InitiativefalseRationale for the selection of dual primary endpoints in prevention studies of cognitively unimpaired individuals at genetic risk for developing symptoms of Alzheimer's disease.<h4>Background</h4>There is a critical need for novel primary endpoints designed to detect early and subtle changes in cognition in clinical trials targeting the asymptomatic (preclinical) phase of Alzheimer's disease (AD). The Alzheimer's Prevention Initiative (API) Generation Program, conducted in cognitively unimpaired individuals at risk of developing AD (e.g., enriched by the apolipoprotein E (APOE) genotype), used a novel dual primary endpoints approach, whereby demonstration of treatment effect in one of the two endpoints is sufficient for trial success. The two primary endpoints were (1) time to event (TTE)-with an event defined as a diagnosis of mild cognitive impairment (MCI) due to AD and/or dementia due to AD-and (2) change from baseline to month 60 in the API Preclinical Compo2023-01-01T00:00:00Z2023 Mar2025-05-18T12:54:35.523Z2025-04-06T09:02:36.328ZS-EPMC99870443687934010.1186/s13195-023-01183-z