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

Insel, Philip S. LU ; Palmqvist, Sebastian LU ; Mackin, R. Scott; Nosheny, Rachel L.; Hansson, Oskar LU ; Weiner, Michael W. and Mattsson, Niklas LU (2016) In Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring 4. p.76-84
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyloid, APOE, Clinical trials, Cognition, Preclinical Alzheimer's
in
Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
volume
4
pages
9 pages
publisher
Elsevier
external identifiers
  • scopus:84988979324
DOI
10.1016/j.dadm.2016.07.002
language
English
LU publication?
yes
id
23ddfeda-567b-4b97-848a-e74eb2ed2aca
date added to LUP
2016-11-03 15:24:03
date last changed
2017-10-01 05:25:18
@article{23ddfeda-567b-4b97-848a-e74eb2ed2aca,
  abstract     = {<p>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.</p>},
  author       = {Insel, Philip S. and Palmqvist, Sebastian and Mackin, R. Scott and Nosheny, Rachel L. and Hansson, Oskar and Weiner, Michael W. and Mattsson, Niklas},
  keyword      = {Amyloid,APOE,Clinical trials,Cognition,Preclinical Alzheimer's},
  language     = {eng},
  pages        = {76--84},
  publisher    = {Elsevier},
  series       = {Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring},
  title        = {Assessing risk for preclinical β-amyloid pathology with APOE, cognitive, and demographic information},
  url          = {http://dx.doi.org/10.1016/j.dadm.2016.07.002},
  volume       = {4},
  year         = {2016},
}