Prediction of future Alzheimer’s disease dementia using plasma phospho‐tau combined with other accessible measures

Abstract

AbstractBackgroundPlasma phospho‐tau (P‐tau) has shown a high diagnostic accuracy for Alzheimer’s disease (AD), but its performance in predicting development of AD dementia and what other measures to combine it with for an optimal predictive accuracy is less known. We examined this using plasma P‐tau combined with other easily accessible measures and compared the results to the clinical diagnostic prediction and to results obtained using cerebrospinal fluid (CSF) biomarkers.MethodWe included patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) who were consecutively recruited in the BioFINDER study (n=340). The results were validated in SCD and MCI participants in the ADNI study (n=543). Plasma P‐tau, plasma Aβ42/Aβ40, plasma neurofilament light, APOE genotype, brief cognitive tests and MRI (cortical thickness in AD‐specific regions) were examined as predictors of progression to AD dementia within 4 years (2 and 6 years were secondary outcomes). The accuracy was determined using the area under the ROC curve (AUC) from logistic regression models.ResultWithin 4 years, plasma P‐tau217 predicted AD dementia accurately (AUC 0.83) in BioFINDER. A model consisting of plasma P‐tau217, memory, executive function, and APOE had higher accuracy (AUC 0.91, p<0.001). In ADNI, this model produced a similar AUC (0.90) using plasma P‐tau181 instead of P‐tau217. A cross‐validated version of this model using binary plasma P‐tau data (normal/abnormal) was implemented online for the prediction of the individual probability of progressing to AD dementia. Parsimonious models had similar accuracies for predicting AD dementia within 2 and 6 years (AUCs 0.90‐0.91 in both cohorts). Using CSF P‐tau, Aβ42/Aβ40 and neurofilament light instead of plasma biomarkers did not improve the accuracy. In BioFINDER, the clinical diagnostic prediction by memory clinic physicians blinded to fluid biomarker data had significantly lower accuracy than all models (4‐year AUC 0.71).ConclusionPlasma P‐tau in combination with brief cognitive tests and APOE genotyping improves the predictive accuracy of whether a patient will progress to AD dementia or remain stable/progress to other dementias, compared to using just plasma P‐tau or to the clinical prediction. Plasma P‐tau combined with these measures may also facilitate recruitment for AD trials.