Abstract
BACKGROUND: Controversy existed in the prognosis of reversion from mild cognitive impairment (MCI) to normal cognition (NC). We aim to depict the prognostic characteristics of cognition, neuroimaging, and pathology biomarkers, as well as the risk of Alzheimer's disease (AD) dementia for MCI reverters. METHODS: A total of 796 non-demented participants (mean age = 73.3 years, female = 54.4%, MCI = 55.7%), who were divided into MCI reverters (n = 109), stable MCI (n = 334), and stable NC (n = 353) based on 2-year diagnosis changes, were subsequently followed up for 6 years. Cox proportional hazard regression models were applied to assess the AD dementia hazard. Linear mixed-effect models were used to evaluate the differences in changing rates of cognitive scores, brain volumes, brain metabolism, and AD biomarkers among three groups. RESULTS: The 2-year MCI reversion rate was 18.17%. MCI reversion was associated with an 89.6% lower risk of AD dementia (HR = 0.104, 95% confidence interval = [0.033, 0.335], p < 0.001) than stable MCI. No significant difference in incident AD risk was found between MCI reverters and stable NC (p = 0.533). Compared to stable MCI, reverters exhibited slower decreases in cognitive performance (false discovery rate corrected p value [FDR-Q] < 0.050), brain volumes (FDR-Q < 0.050), brain metabolism (FDR-Q < 0.001), and levels of cerebrospinal fluid β-amyloid(1-42) (FDR-Q = 0.008). The above-mentioned differences were not found between MCI reverters and stable NC (FDR-Q > 0.050). CONCLUSIONS: Reversion from MCI to NC predicts a favorable prognosis of pathological, neurodegenerative, and cognitive trajectory.