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

Philip S Insel; Sebastian Palmqvist; R Scott Mackin; Rachel L Nosheny; Oskar Hansson; Michael W Weiner; Niklas Mattsson

doi:10.1016/j.dadm.2016.07.002

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

Alzheimers Dement (Amst). 2016 Aug 3:4:76-84. doi: 10.1016/j.dadm.2016.07.002. eCollection 2016.

Authors

Philip S Insel¹, Sebastian Palmqvist², R Scott Mackin³, Rachel L Nosheny⁴, Oskar Hansson⁵, Michael W Weiner⁶, Niklas Mattsson²

Affiliations

¹ Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden; Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
² Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden.
³ Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, CA, USA.
⁴ Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA, USA.
⁵ Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden.
⁶ Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

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 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.

Keywords: APOE; Amyloid; Clinical trials; Cognition; Preclinical Alzheimer's.

Abstract

Grants and funding