Assessing risk for preclinical β-amyloid pathology with APOE, cognitive, and demographic information

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T1 - Assessing risk for preclinical β-amyloid pathology with APOE, cognitive, and demographic information

AU - Insel, Philip S.

AU - Palmqvist, Sebastian

AU - Mackin, R. Scott

AU - Nosheny, Rachel L.

AU - Hansson, Oskar

AU - Weiner, Michael W.

AU - Mattsson, Niklas

PY - 2016

Y1 - 2016

N2 - Introduction Clinical trials in Alzheimer's disease are aimed at early stages of disease, including preclinical Alzheimer's disease. The high cost and time required to screen large numbers of participants for Aβ pathology impede the development of novel drugs. This study's objective was to evaluate the extent to which inexpensive and easily obtainable information can reduce the number of screen failures by increasing the proportion of Aβ+ participants identified for screening. Methods We used random forest models to evaluate the positive predictive value of demographics, APOE, and longitudinal cognitive rates in the prediction of amyloid pathology, measured by florbetapir PET or cerebrospinal fluid. Results Predicting Aβ positivity with demographic, APOE, and cognitive information yielded a positive predictive value estimate of 0.65 (95% CI, 0.50–0.96), nearly a 60% increase over the reference Aβ+ prevalence in the cohort of 0.41. Conclusions By incorporating this procedure, clinical trial screening costs of 7500 USD per participant may be reduced by nearly 7 million USD total.

AB - Introduction Clinical trials in Alzheimer's disease are aimed at early stages of disease, including preclinical Alzheimer's disease. The high cost and time required to screen large numbers of participants for Aβ pathology impede the development of novel drugs. This study's objective was to evaluate the extent to which inexpensive and easily obtainable information can reduce the number of screen failures by increasing the proportion of Aβ+ participants identified for screening. Methods We used random forest models to evaluate the positive predictive value of demographics, APOE, and longitudinal cognitive rates in the prediction of amyloid pathology, measured by florbetapir PET or cerebrospinal fluid. Results Predicting Aβ positivity with demographic, APOE, and cognitive information yielded a positive predictive value estimate of 0.65 (95% CI, 0.50–0.96), nearly a 60% increase over the reference Aβ+ prevalence in the cohort of 0.41. Conclusions By incorporating this procedure, clinical trial screening costs of 7500 USD per participant may be reduced by nearly 7 million USD total.

KW - Amyloid

KW - APOE

KW - Clinical trials

KW - Cognition

KW - Preclinical Alzheimer's

UR - http://www.scopus.com/inward/record.url?scp=84988979324&partnerID=8YFLogxK

U2 - 10.1016/j.dadm.2016.07.002

DO - 10.1016/j.dadm.2016.07.002

M3 - Article

VL - 4

SP - 76

EP - 84

JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

T2 - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

SN - 2352-8729

ER -