biostudies-literatureSpencer BENIA NIH HHSAlzheimer&apos;s Disease Neuroimaging InitiativeNational Institutes of HealthNational Institute on AgingNIH HHSNational Institute of Biomedical Imaging and Bioengineering457-465https://www.ebi.ac.uk/biostudies/studies/S-EPMC8906231biostudies-literatureUnknown17(3)<h4>Introduction</h4>Elevated β-amyloid is used to enroll individuals into preclinical Alzheimer's disease trials, but the screening process is inefficient and expensive. Novel enrichment methods are needed to improve efficiency of enrollment.<h4>Methods</h4>Alzheimer's disease incidence rates and a polygenic hazard score were used to create a gene- and age-defined ADAge. An ADAge cutpoint was chosen to optimally predict β-amyloid positivity among clinically normal Alzheimer's Disease Neuroimaging Initiative participants and applied to an independent Alzheimer's Disease Research Center validation cohort. The impact of ADAge enrichment on screening costs was evaluated in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease trial data.<h4>Results</h4>In the validation cohort, the ADAge-enriched sample had a higher proportion of individuals with elevated β-amyloid (difference [95% CI] 0.19[0.07 to 0.33]) than the unenriched sample. ADAge enrichment lowered screening costs by $4.41 million (31.00%) in the real-world clinical trial scenario.<h4>Discussion</h4>ADAge enrichment provides for a more efficient and cost-effective means to enroll clinically normal individuals with elevated β-amyloid in clinical trials.Alzheimer's & dementia : the journal of the Alzheimer's AssociationGene- and age-informed screening for preclinical Alzheimer's disease trials.PMC8906231P30 AG028383P30 AG013846P30 AG008017P30 AG053760P30 AG010133P50 AG0051461P30‐AG062429‐01P50 AG005142P50 AG005681U19 AG010483P30 AG062715P50 AG047366P50 AG047266P30 AG019610P50 AG023501R01 AG063689P30 AG008051P30 AG010129P30 AG013854P50 AG005138P50 AG008702P30 AG0624281P30-AG062429-01P30 AG010124P30 AG012300P50 AG047270U01 AG016976P50 AG025688P30 AG062421P50 AG005136P30 AG062422P30 AG035982P30 AG010161P50 AG005133P30 AG062429P30 AG049638U24 AG072122U01 AG024904P50 AG016573Digma LAAlzheimer's Disease Neuroimaging Initiative and the A4 Study TeamJennings RGBrewer JBSpencer BEfalseGene- and age-informed screening for preclinical Alzheimer's disease trials.<h4>Introduction</h4>Elevated β-amyloid is used to enroll individuals into preclinical Alzheimer's disease trials, but the screening process is inefficient and expensive. Novel enrichment methods are needed to improve efficiency of enrollment.<h4>Methods</h4>Alzheimer's disease incidence rates and a polygenic hazard score were used to create a gene- and age-defined ADAge. An ADAge cutpoint was chosen to optimally predict β-amyloid positivity among clinically normal Alzheimer's Disease Neuroimaging Initiative participants and applied to an independent Alzheimer's Disease Research Center validation cohort. The impact of ADAge enrichment on screening costs was evaluated in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease trial data.<h4>Results</h4>In the validation cohort, the ADAge-enriched sample had a higher proportion of individuals with elevated β-amyloid (difference [95% CI] 0.19[0.07 to 0.33]) than the unenriched sample. ADAge enrichment lowered screening costs by $4.41 million (31.00%) in the real-world clinical trial scenario.<h4>Discussion</h4>ADAge enrichment provides for a more efficient and cost-effective means to enroll clinically normal individuals with elevated β-amyloid in clinical trials.2021-01-01T00:00:00Z2021 Mar2025-04-26T03:56:00.296Z2025-04-06T10:59:30.293ZS-EPMC89062313322672310.1002/alz.12207