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. 2023;96(1):265-275.
doi: 10.3233/JAD-230524.

Reconceptualization of the Erlangen Score for the Assessment of Dementia Risk: The ERlangen Score

Janine Utz  1 , Pauline Olm  1 , Johannes Jablonowski  1 , Eva-Maria Siegmann  1 , Philipp Spitzer  1 , Piotr Lewczuk  1   2 , Johannes Kornhuber  1 , Juan Manuel Maler  1 , Timo Jan Oberstein  1
Affiliations

Reconceptualization of the Erlangen Score for the Assessment of Dementia Risk: The ERlangen Score

Janine Utz et al. J Alzheimers Dis. 2023.

Abstract

Background: The established Erlangen Score (ES) for the interpretation of cerebrospinal fluid (CSF) biomarkers in the diagnostics of Alzheimer's disease (AD) uses markers of amyloidopathy and tauopathy, equally weighted to form an easy-interpretable ordinal scale. However, these biomarkers are not equally predictive for AD.

Objective: The higher weighting of the Aβ42/Aβ40 ratio, as a reconceptualized ERlangen Score (ERS), was tested for advantages in diagnostic performance.

Methods: Non-demented subjects (N = 154) with a mean follow up of 5 years were assigned to a group ranging from 0 to 4 in ES or ERS. Psychometric trajectories and dementia risk were assessed.

Results: The distribution of subjects between ES and ERS among the groups differed considerably, as grouping allocated 32 subjects to ES group 2, but only 2 to ERS group 2. The discriminative accuracy between the ES (AUC 73.2%, 95% CI [64.2, 82.2]) and ERS (AUC 72.0%, 95% CI [63.1, 81.0]) for dementia risk showed no significant difference. Without consideration of the Aβ42/Aβ40 ratio in ES grouping, the optimal cut-off of the ES shifted to ≥2.

Conclusions: The ERS showed advantages over the ES in test interpretation with comparable overall test performance, as fewer cases were allocated to the intermediate risk group. The established cut-off of ≥2 can be maintained for the ERS, whereas it must be adjusted for the ES when determining the Aβ42/Aβ40 ratio.

Keywords: Alzheimer’s disease; Erlangen Score; dementia risk; longitudinal study; neuropsychological trajectories.

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Conflict of interest statement

PL received consultation and/or lecture honoraria from IBL International, Fujirebio Europe, AJ Roboscreen, Biogen, and Roche. PL is an Editorial Board Member of this journal but was not involved in the peer-review process nor had access to any information regarding its peer-review. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Comparison of the grouping of the study population using the established Erlangen Score (ES) and the reconceptualized ERlangen Score (ERS). The ES was calculated with (A) and without (B) consideration of the Aβ42/Aβ40 ratio. The ERS was calculated in two steps. In step 1, the score is calculated as in the ES, but without considering the Aβ42/Aβ40 ratio, i.e., as in Fig. 1B. In the second step, in case of a pathological or normal Aβ42/Aβ40 ratio, +1 or –1 is added, provided the value is not below 0 or exceeds 4. By changing the weighting of the Aβ42/Aβ40 ratio in the ERS, substantially fewer participants were assigned to the intermediary risk group (yellow group) compared to the ES. The score of the ES can be derived by summing values for amyloidopathy and tauopathy (0 = normal, 1 = borderline pathological, 2 = definitive pathological). Colors indicate assumed dementia risk: low (green), mild (light green), intermediate (yellow), increased (orange) or probable (red).
Fig. 2
Fig. 2
Cognitive trajectories by Erlangen Score (ES) and ERlangen Score (ERS). For all CERAD-NB+subtests shown, the z-score was used for the linear mixed-effects model analyses of the ES (left) and the ERS (right). The cognitive trajectories are not shown for ERS group 2 because it included only two individuals. Exact p-values and 95% confidence interval are given in Supplementary Table 1. MMSE, z-score of the Mini-Mental State Examination; σ, standard deviation.
Fig. 3
Fig. 3
Comparison of dementia risk between the Erlangen Score (ES) and the reconceptualized ERlangen Score (ERS). Kaplan-Meier curves show the risk of dementia onset in nondemented individuals by ES (A) and ERS groups (B). Nondemented individuals with an ES of 1 or 2 showed no increased risk of dementia onset compared with controls. For both ES and ERS, dementia risk was increased in groups 3 and 4. This was confirmed when comparing hazard ratios for the occurrence of dementia between groups 1 to 4 versus the control group in a univariate and a multivariate Cox regression model with age, education and MMSE at baseline as covariates for the ES (C) and the ERS (D).
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