BackgroundThe role of amyloid-β (Aβ) and tau in reversion and conversion in patients with mild cognitive impairment (MCI) remains unclear. This study aimed to investigate the influence of cerebrospinal fluid (CSF) Aβ and tau on reversion and conversion and the temporal sequence of their pathogenicity in MCI patients. Methods179 MCI patients were recruited from the Alzheimer's Disease Neuroimaging Initiative database and classified into two groups based on cognitive changes after follow-up: reversal group (MCI to cognitively normal) and conversion group (MCI to Alzheimer's disease). CSF biomarkers and cognitive function were measured at baseline and 2-year follow-up. Partial correlation was used to analyze the association between CSF biomarkers and cognitive function, and multivariable logistic regression to identify independent risk factors for cognitive changes at baseline and 2-year follow-up. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive ability of these risk factors for cognitive changes. ResultsThe differences in cognitive function and CSF biomarkers between the two groups remained consistent with baseline after 2-year follow-up. After controlling for confounding variables, there was still a correlation between CSF biomarkers and cognitive function at baseline and 2-year follow-up. Multivariable regression analysis found that at baseline, only Aβ level was independently associated with cognitive changes, while Aβ and tau were both predictive factors after 2-year follow-up. ROC curve analysis revealed that the combination of Aβ and tau [area under the curve (AUC) 0.91, sensitivity 84%, specificity 86%] in predicting cognitive changes after 2-year follow-up had better efficacy than baseline Aβ alone (AUC 0.81). ConclusionAβ may precede Tau in causing cognitive changes, and the interaction between the two mediates cognitive changes in patients. This study provides new clinical evidence to support the view that Aβ pathology precedes tau pathology, which together contribute to the changes in cognitive function.