Determining Cut-Points for Alzheimer’s Disease Biomarkers: Statistical Issues, Methods and Challenges
Open Access
- 23 August 2012
- journal article
- review article
- Published by Informa UK Limited in Biomarkers in Medicine
- Vol. 6 (4), 391-400
- https://doi.org/10.2217/bmm.12.49
Abstract
New proposed criteria for the clinical diagnosis of Alzheimer’s disease increasingly incorporate biomarkers, most of which are normally measured on a continuous scale. Operationalizing such criteria thus requires continuous biomarkers to be dichotomized, which in turns requires the selection of a cut-point at which to dichotomize. In this article, we review the statistical principles underlying the choice of cut-points, describe some of the most commonly adopted statistical approaches used to estimate cut-points, highlight potential pitfalls in some of the approaches and characterize in what sense the estimated cut-point from each approach is optimal. We also emphasize that how a cut-point is selected must be made in reference to how the resulting dichotomized biomarker is to be used, and in particular what actions will follow from a positive or negative test result.Keywords
This publication has 20 references indexed in Scilit:
- Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's diseaseAlzheimer's & Dementia, 2011
- Increased brain atrophy rates in cognitively normal older adults with low cerebrospinal fluid Aβ1‐42Annals of Neurology, 2010
- Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascadeThe Lancet Neurology, 2010
- CSF Biomarkers and Incipient Alzheimer Disease in Patients With Mild Cognitive ImpairmentJAMA, 2009
- Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjectsAnnals of Neurology, 2009
- Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteriaThe Lancet Neurology, 2007
- Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up studyThe Lancet Neurology, 2006
- Uses and abuses of screening testsThe Lancet, 2002
- Tau and Aβ42 in Cerebrospinal Fluid from Healthy Adults 21–93 Years of Age: Establishment of Reference ValuesClinical Chemistry, 2001
- Evaluation of CSF-tau and CSF-Aβ42 as Diagnostic Markers for Alzheimer Disease in Clinical PracticeArchives of Neurology, 2001