4.7 Article

A prediction model to calculate probability of Alzheimer's disease using cerebrospinal fluid biomarkers

Journal

ALZHEIMERS & DEMENTIA
Volume 9, Issue 3, Pages 262-268

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2012.01.010

Keywords

Prediction model; Dementia; CSF biomarkers; Differential diagnosis; Validation

Funding

  1. Netherlands Heart Foundation
  2. NWO (Netherlands Organisation for Scientific Research)
  3. Ferring Netherlands
  4. Abbott Diagnostics
  5. European Union
  6. Dutch MS Society
  7. Lundbeck
  8. Danone Research
  9. Stichting Internationaal Parkinson Fonds
  10. Van Alkemade-Keuls Fonds
  11. American Alzheimer's Association
  12. Alzheimer Drug Discovery Foundation
  13. Aromatic Amino Acid Decarboxylase Deficiency Research Trust, Hersenstichting Nederland

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Background: We aimed to develop a prediction model based on cerebrospinal fluid (CSF) biomarkers, that would yield a single estimate representing the probability that dementia in a memory clinic patient is due to Alzheimer's disease (AD). Methods: All patients suspected of dementia in whom the CSF biomarkers had been analyzed were selected from a memory clinic database. Clinical diagnosis was AD (n = 272) or non-AD (n = 289). The prediction model was developed with logistic regression analysis and included CSF amyloid beta(42), CSF phosphorylated tau(181), and sex. Validation was performed on an independent data set from another memory clinic, containing 334 AD and 157 non-AD patients. Results: The prediction model estimated the probability that AD is present as follows: p(AD) = 1/(1 + e(- [-0.3315 + score])) where score is calculated from -1.9486 X ln(amyloid beta(42)) + 2.7915 X ln(phosphorylated tau(181)) + 0.9178 X sex (male = 0, female = 1). When applied to the validation data set, the discriminative ability of the model was very good (area under the receiver operating characteristic curve: 0.85). The agreement between the probability of AD predicted by the model and the observed frequency of AD diagnoses was very good after taking into account the difference in AD prevalence between the two memory clinics. Conclusions: We developed a prediction model that can accurately predict the probability of AD in a memory clinic population suspected of dementia based on CSF amyloid beta(42), CSF phosphorylated tau(181), and sex. (C) 2013 The Alzheimer's Association. All rights reserved.

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