Gene- and age-informed screening for preclinical Alzheimer's disease trials.
Alzheimers Dement
; 17(3): 457-465, 2021 03.
Article
en En
| MEDLINE
| ID: mdl-33226723
ABSTRACT
INTRODUCTION:
Elevated ß-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.METHODS:
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 ß-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.RESULTS:
In the validation cohort, the ADAge-enriched sample had a higher proportion of individuals with elevated ß-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.DISCUSSION:
ADAge enrichment provides for a more efficient and cost-effective means to enroll clinically normal individuals with elevated ß-amyloid in clinical trials.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tamizaje Masivo
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Péptidos beta-Amiloides
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Enfermedad de Alzheimer
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Síntomas Prodrómicos
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Límite:
Aged
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Female
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Humans
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Male
Idioma:
En
Año:
2021
Tipo del documento:
Article