Estimating Bidirectional Transitions and Identifying Predictors of Mild Cognitive Impairment

Background and Objectives Various resources exist for treating mild cognitive impairment (MCI) or dementia separately as terminal events or for focusing solely on a 1-way path from MCI to dementia without taking into account heterogeneous transitions. Little is known about the trajectory of reversion from MCI to normal cognition (NC) or near-NC and patterns of postreversion, which refers to cognitive trajectories of patients who have reversed from MCI to NC. Our objectives were to (1) quantitatively predict bidirectional transitions of MCI (reversion and progression), (2) explore patterns of future cognitive trajectories for postreversion, and (3) estimate the effects of demographic characteristics, APOE, cognition, daily activity ability, depression, and neuropsychiatric symptoms on transition probabilities.

Methods We constructed a retrospective cohort by reviewing patients with an MCI diagnosis at study entry and at least 2 follow-up visits between June 2005 and February 2021. Defining NC or near-NC and MCI as transient states and dementia as an absorbing state, we used continuous-time multistate Markov models to estimate instantaneous transition intensity between states, transition probabilities from one state to another at any given time during follow-up, and hazard ratios of reversion-related variables.

Results Among 24,220 observations from 6,651 participants, there were 2,729 transitions to dementia and 1,785 reversions. As for postreversion, there were 630 and 73 transitions of progression to MCI and dementia, respectively. The transition intensity of progression to MCI for postreversion was 0.317 (2.48-fold greater than that for MCI progression or reversion). For postreversion participants, the probability of progressing to dementia increased by 2% yearly. Participants who progressed to MCI were likely to reverse again (probability of 40% over 15 years). Age, independence level, APOE, cognition, daily activity ability, depression, and neuropsychiatric symptoms were significant predictors of bidirectional transitions.

Discussion The nature of bidirectional transitions cannot be ignored in multidimensional MCI research. We found that postreversion participants remained at an increased risk of progression to MCI or dementia over the longer term and experienced recurrent reversions. Our findings may serve as a valuable reference for future research and enable health care professionals to better develop proactive management plans and targeted interventions.