Abstract
BACKGROUND: Low cerebrospinal fluid (CSF) amyloid-beta 1-42 (A beta 1-42) concentrations indicate amyloid plaque accumulation in the brain, a pathological hallmark of Alzheimer disease (AD). Innotest assay values of A beta 1-42 have gradually increased over the past 2 decades, which might lead to misclassification of AD when a single cutpoint for abnormality is used. We propose an unbiased approach to statistically correct for drift. METHODS: We determined year-specific cutpoints with Gaussian mixture modeling, based on the cross-section of bimodal distributions of A beta 1-42 concentrations in 4397 memory clinic patients. This allowed us to realign year-specific cutpoints as an unbiased method to remove drift from the data. Sensitivity and specificity to detect AD dementia were compared between corrected and uncorrected values. RESULTS: A beta 1-42 values increased 22 pg/mL annually, and this could not be explained by changes in cohort composition. Our approach removed time dependencies [beta (SE) -0.07 (0.59); P = 0.91]. Statistically correcting for drift improved the sensitivity to detect AD dementia to 0.90 (95% CI, 0.89-0.92) from at least 0.66 (95% CI, 0.64-0.69) based on uncorrected data. Specificity became lower (0.69; 95% CI, 0.67-0.70) vs at most 0.80 (95% CI, 0.79-0.82) for uncorrected data. CONCLUSIONS: This approach may also be useful to standardize A beta 1-42 CSF concentrations across different centers and/or platforms, and to optimize use of CSF biomarker data collected over a long period. (c) 2017 American Association for Clinical Chemistry
Original language | English |
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Pages (from-to) | 576-585 |
Number of pages | 10 |
Journal | Clinical Chemistry |
Volume | 64 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Mar 2018 |
Keywords
- ALZHEIMERS ASSOCIATION WORKGROUPS
- MILD COGNITIVE IMPAIRMENT
- DIAGNOSTIC GUIDELINES
- NATIONAL INSTITUTE
- PIB-PET
- DISEASE
- BIOMARKERS
- DEMENTIA
- RECOMMENDATIONS
- OLIGOMERIZATION