Comparison of ERlangen Score with pTau/Aβ1-42 Ratio for Predicting Cognitive Decline and Conversion to Alzheimer's...

Background/Objectives: The ERlangen Score (ERS) and the pTau/Aβ1-42 ratio are dementia risk scores that use only surrogate markers of amyloid and tau pathology, whose performance has taken on added importance with the advent of anti-amyloid antibody therapies. Direct comparisons between the scores are limited, which is why the performance of the ERlangen Score (ERS) and the pTau/Aβ1-42 ratio in predicting cognitive decline and dementia risk were compared. Methods: Measurements of Aβ1-42, Aβ1-40, and pTau181 were conducted in cerebrospinal fluid samples using immunoassays. Linear mixed models and the area under the receiver operating characteristic curve (AUC, receiver operating characteristic = ROC) of 259 non-demented subjects were calculated. Results: The pTau/Aβ1-42 ratio correctly identified 55 out of 60 individuals with a positive Aβ1-42/Aβ1-40 ratio and pTau181 as having Alzheimer's disease (AD), while the ERS correctly identified all of these individuals. The model using the ERS to predict cognitive trajectories (Akaike Information Criterion AIC = 2365) exhibited a marginally superior fit than the model using the pTau/Aβ1-42 ratio (AIC = 2371). There was no statistically significant difference in the AUC of the ERS (0.717) for dementia risk compared to the pTau/Aβ1-42 ratio (0.739), p = 0.179. However, when the Aβ1-42/Aβ1-40 ratio was not included in the ERS (AUC = 0.685), the pTau/Aβ1-42 score was found to be statistically significantly better, p = 0.007. Conclusions: The ERS showed an advantage in grouping, identifying all patients with a positive Aβ1-42/Aβ1-40 ratio and elevated pTau181 as having AD. The ERS and pTau/Aβ1-42 ratio were comparable in predicting dementia or cognitive decline. However, when the Aβ1-42/Aβ1-40 ratio is not available, the pTau/Aβ1-42 ratio should be preferred.