Gene- and age-informed screening for preclinical Alzheimer's disease trials
| Autor: | Robin G. Jennings, Alzheimer’s Disease Neuroimaging Initiative, James B. Brewer, Leonardino A. Digma, Barbara E. Spencer |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Epidemiology Prodromal Symptoms Disease Asymptomatic Article Cohort Studies 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Developmental Neuroscience Adage Alzheimer Disease Internal medicine Medicine Humans Mass Screening Aged Clinical Trials as Topic Amyloid beta-Peptides business.industry Health Policy Clinical study design Brain Enrichment methods Clinical trial Psychiatry and Mental health 030104 developmental biology Positron-Emission Tomography Female Neurology (clinical) Geriatrics and Gerontology medicine.symptom business Validation cohort 030217 neurology & neurosurgery |
| Zdroj: | Alzheimers Dement |
| ISSN: | 1552-5279 |
| Popis: | Introduction 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. 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 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. Results 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. Discussion ADAge enrichment provides for a more efficient and cost-effective means to enroll clinically normal individuals with elevated β-amyloid in clinical trials. |
| Databáze: | OpenAIRE |
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