Unbiased estimates of cerebrospinal fluid beta-amyloid 1-42 cutoffs in a large memory clinic population

Daniela Bertens, Betty M. Tijms, Philip Scheltens, Charlotte E. Teunissen, Pieter Jelle Visser*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: We sought to define a cutoff for beta-amyloid 1-42 in cerebrospinal fluid (CSF), a key marker for Alzheimer's disease (AD), with data-driven Gaussian mixture modeling in a memory clinic population.

Methods: We performed a combined cross-sectional and prospective cohort study. We selected 2462 subjects with subjective cognitive decline, mild cognitive impairment, AD-type dementia, and dementia other than AD from the Amsterdam Dementia Cohort. We defined CSF beta-amyloid 1-42 cutoffs by data-driven Gaussian mixture modeling in the total population and in subgroups based on clinical diagnosis, age, and apolipoprotein E (APOE) genotype. We investigated whether abnormal beta-amyloid 1-42 as defined by the data-driven cutoff could better predict progression to AD-type dementia than abnormal beta-amyloid 1-42 defined by a clinical diagnosis-based cutoff using Cox proportional hazards regression.

Results: In the total group of patients, we found a cutoff for abnormal CSF beta-amyloid 1-42 of 680 pg/ml (95% CI 660-705 pg/ml). Similar cutoffs were found within diagnostic and APOE genotype subgroups. The cutoff was higher in elderly subjects than in younger subjects. The data-driven cutoff was higher than our clinical diagnosisbased cutoff and had a better predictive accuracy for progression to AD-type dementia in nondemented subjects (HR 7.6 versus 5.2, p <0.01).

Conclusions: Mixture modeling is a robust method to determine cutoffs for CSF beta-amyloid 1-42. It might better capture biological changes that are related to AD than cutoffs based on clinical diagnosis.

Original languageEnglish
Article number8
Number of pages8
JournalAlzheimer's Research & Therapy
Volume9
DOIs
Publication statusPublished - 14 Feb 2017

Keywords

  • Alzheimer's disease
  • MCI
  • Cerebrospinal fluid
  • Diagnosis
  • MILD COGNITIVE IMPAIRMENT
  • ALZHEIMERS ASSOCIATION WORKGROUPS
  • PROGRESSIVE SUPRANUCLEAR PALSY
  • DIAGNOSTIC-CRITERIA
  • FRONTOTEMPORAL DEMENTIA
  • INTERNATIONAL WORKSHOP
  • NATIONAL INSTITUTE
  • DISEASE
  • BIOMARKERS
  • PET

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