Date Published: January 5, 2019
Publisher: BioMed Central
Author(s): Inês Baldeiras, Isabel Santana, Maria João Leitão, Daniela Vieira, Diana Duro, Barbara Mroczko, Johannes Kornhuber, Piotr Lewczuk.
The previously described and validated Erlangen Score (ES) algorithm enables interpretation of the cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD), ordering them on an ordinal scale: from neurochemically normal (ES = 0) through improbable AD (ES = 1), possible AD (ES = 2 or 3), to probable AD (ES = 4). Here we assess the accuracy of the ES in predicting hazards of progression from the mild cognitive impairment (MCI) stage of AD to the dementia stage of the disease (Alzheimer’s disease dementia (ADD)) in a novel, single-center cohort.
Baseline CSF biomarkers (amyloid beta (Aβ) 1–42, Aβ42/40, Tau, and pTau181), interpreted according to the ES, were used to estimate time to progression from the MCI stage of AD to ADD, conditional on age, gender, APOE ε4 genotype, and Mini Mental State Examination score in 144 MCI subjects, using the Extended Cox Model; the subjects were followed-up until they developed dementia or until they had been cognitively stable for at least 2 years. In addition, ES distributions were studied in 168 ADD cases and 66 neurologic controls.
The distributions of the ES categories across the four diagnostic groups (Controls, MCI-Stable, MCI-AD, and ADD) were highly significantly different (Kruskal–Wallis χ2(df = 3) = 151.4, p < 0.001), with significant contrasts between each pair (p < 0.005), except between the ADD and the MCI-AD groups (p = 1.0). MCI patients with ES = 2 or 3 had 6–8 times higher hazards to progress to ADD compared to patients with ES = 0 or 1 in the first 3 follow-up years, and then their hazards decreased to those of the group with ES = 0 or 1. Patients with ES = 4 had hazards 8–12 times higher compared to the ES = 0 or 1 group. Faster progressors with ES = 2 or 3 had, in comparison to slower progressors, significantly lower Aβ1–42, Aβ1–40, and Aβ42/40, but comparable Tau and pTau181. A highly significant difference of the ES distributions between these two groups was observed (p < 0.001). Our current results reconfirm and extend the conclusions of the previously published report that the Erlangen Score is a useful tool facilitating interpretation of a complex pattern of the CSF AD biomarkers. The online version of this article (10.1186/s13195-018-0456-x) contains supplementary material, which is available to authorized users.
Decreased concentration of amyloid beta (Aβ) 1–42 peptide, decreased Aβ42/40 ratio, and increased Tau and pTau181 concentrations in cerebrospinal fluid (CSF) form the biomarker profile in Alzheimer’s disease (AD) . This pattern reflects the two pathophysiologic processes of the disease: amyloidosis and neurodegeneration. Although the CSF biomarkers demonstrate very high diagnostic accuracy, and are routinely used as an AD diagnostics tool in some countries, their further acceptance is hampered by problems with comparability of the results obtained in different centers or even in one center but with different analytical platforms. This issue has already been addressed, to some extent, by efforts to standardize procedures for sample collection, measurements protocols and assay calibrators, but global acceptance of these novel approaches will certainly take time [2–5]. Moreover, as the AD CSF biomarkers are progressively used in daily clinical practice, interpretation of the results needs expertise and caution and the question remains how to interpret the information given by the biomarkers, that is often heterogeneous, with not all biomarkers falling into clear-cut normal/abnormal categories.
In this study, we confirmed our working hypothesis that the hazard of progression from the MCI stage to the dementia stage in AD strongly depends on the CSF biomarker pattern interpreted according to the Erlangen Score, and hence that the ES is a helpful tool as a predictor of dementia development in MCI subjects.
Our results reconfirm and extend the conclusions of the previously published report that the Erlangen Score is a useful tool facilitating interpretation of a complex pattern of the CSF AD biomarkers; particularly, the Erlangen Score helps to understand CSF patterns in MCI patients progressing to AD dementia.