Dissecting the clinical and pathological prognosis of MCI patients who reverted to normal cognition: a longitudinal study

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...

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Main Authors: Hai-Hong Yu, Lan Tan, Meng-Jiao Jiao, Yi-Ju Lv, Xin-Hao Zhang, Chen-Chen Tan, Wei Xu, for the Alzheimer’s Disease Neuroimaging Initiative
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Medicine
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Online Access:https://doi.org/10.1186/s12916-025-04092-0
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author Hai-Hong Yu
Lan Tan
Meng-Jiao Jiao
Yi-Ju Lv
Xin-Hao Zhang
Chen-Chen Tan
Wei Xu
for the Alzheimer’s Disease Neuroimaging Initiative
author_facet Hai-Hong Yu
Lan Tan
Meng-Jiao Jiao
Yi-Ju Lv
Xin-Hao Zhang
Chen-Chen Tan
Wei Xu
for the Alzheimer’s Disease Neuroimaging Initiative
author_sort Hai-Hong Yu
collection DOAJ
description 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-amyloid1–42 (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.
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spelling doaj-art-bac342e71c7f46ad87eff58bcf653aca2025-08-20T02:15:07ZengBMCBMC Medicine1741-70152025-05-0123111310.1186/s12916-025-04092-0Dissecting the clinical and pathological prognosis of MCI patients who reverted to normal cognition: a longitudinal studyHai-Hong Yu0Lan Tan1Meng-Jiao Jiao2Yi-Ju Lv3Xin-Hao Zhang4Chen-Chen Tan5Wei Xu6for the Alzheimer’s Disease Neuroimaging InitiativeDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityMedical College, Qingdao UniversityMedical College, Qingdao UniversityMedical College, Qingdao UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityAbstract 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-amyloid1–42 (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.https://doi.org/10.1186/s12916-025-04092-0Mild cognitive impairment; Reversion; Dementia; Prognosis; Biomarker
spellingShingle Hai-Hong Yu
Lan Tan
Meng-Jiao Jiao
Yi-Ju Lv
Xin-Hao Zhang
Chen-Chen Tan
Wei Xu
for the Alzheimer’s Disease Neuroimaging Initiative
Dissecting the clinical and pathological prognosis of MCI patients who reverted to normal cognition: a longitudinal study
BMC Medicine
Mild cognitive impairment; Reversion; Dementia; Prognosis; Biomarker
title Dissecting the clinical and pathological prognosis of MCI patients who reverted to normal cognition: a longitudinal study
title_full Dissecting the clinical and pathological prognosis of MCI patients who reverted to normal cognition: a longitudinal study
title_fullStr Dissecting the clinical and pathological prognosis of MCI patients who reverted to normal cognition: a longitudinal study
title_full_unstemmed Dissecting the clinical and pathological prognosis of MCI patients who reverted to normal cognition: a longitudinal study
title_short Dissecting the clinical and pathological prognosis of MCI patients who reverted to normal cognition: a longitudinal study
title_sort dissecting the clinical and pathological prognosis of mci patients who reverted to normal cognition a longitudinal study
topic Mild cognitive impairment; Reversion; Dementia; Prognosis; Biomarker
url https://doi.org/10.1186/s12916-025-04092-0
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