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. 2017 Feb 14;9(1):8.
doi: 10.1186/s13195-016-0233-7.

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

Daniela Bertens  1   2 , Betty M Tijms  1   2 , Philip Scheltens  1   2 , Charlotte E Teunissen  3 , Pieter Jelle Visser  4   5   6
Affiliations

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

Daniela Bertens et al. Alzheimers Res Ther. .

Abstract

Background: We sought to define a cutoff for β-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 β-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 β-amyloid 1-42 as defined by the data-driven cutoff could better predict progression to AD-type dementia than abnormal β-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 β-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 diagnosis-based 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 β-amyloid 1-42. It might better capture biological changes that are related to AD than cutoffs based on clinical diagnosis.

Keywords: Alzheimer’s disease; Cerebrospinal fluid; Diagnosis; MCI.

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Figures

Fig. 1
Fig. 1
Cerebrospinal fluid β-amyloid 1–42 (Aβ42) cutoff values based on mixture modeling. a Total sample. b Demented subjects. c Nondemented subjects. d Subjects with subjective cognitive decline (SCD). e Subjects with mild cognitive impairment (MCI). f Subjects ≤66.5 years old. g Subjects >66.5 years old. h Apolipoprotein E (APOE) ε4 allele noncarriers. i APOE ε4 allele carriers. Subjects with a clinical diagnosis of Alzheimer’s disease (AD)-type dementia at baseline or at follow-up (nondemented subjects) are shown in gray
Fig. 2
Fig. 2
Cerebrospinal fluid β-amyloid 1–42 (Aβ42) cutoff values based on mixture modeling in subjects seen between 2001 and 2007. Subjects with a clinical diagnosis of Alzheimer’s disease (AD)-type dementia at baseline or at follow-up are shown in gray
See this image and copyright information in PMC

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