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Gene‐ and age‐informed screening for preclinical Alzheimer's disease trials
Author(s) -
Spencer Barbara E.,
Digma Leonardino A.,
Jennings Robin G.,
Brewer James B.
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12207
Subject(s) - medicine , alzheimer's disease neuroimaging initiative , clinical trial , disease , asymptomatic , cohort , alzheimer's disease , hazard ratio , cohort study , amyloid (mycology) , oncology , pathology , confidence interval
Abstract 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.