Estimating Bidirectional Transitions and Identifying Predictors of Mild Cognitive Impairment

Abstract

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.

Figure 1. Possible Transition Paths for the Selected Participants (A) and Transitions Numbers Between Transient States (

(A) Possible transition paths for 3 selected participants. We truncated observations after the diagnosis of dementia. The filled circles indicate actual observations. The solid line is a possible transition path during the follow-up period. The possible transition paths were randomly selected on the basis of the observed states. (B) Schema of the Markov model specified in this study. The arrows in the figure specify possible transitions between these states. Each transition parameter q indicates the transition intensity; that is, q_ij is interpreted as an instantaneous risk of transition from state i to j. MCI = mild cognitive impairment; <MCI = no impairment or any impairment falling below the MCI criteria threshold; MMSE = Mini-Mental State Examination.

Figure 2. Transition Probability Curves and Estimated Percentage of Total Length of Stay for 3 States Over 15 years in 3 Different Scenarios

(A) Corresponds to the scenario in which NC and impaired but not MCI are merged, (B) corresponds to the scenario in which impaired but not MCI is excluded, and (C) corresponds to the scenario in which impaired but not MCI is treated as an independent transient state. MCI = mild cognitive impairment; NC = normal cognition.

Figure 3. Transition Probability Curves for Participants With aMCI and naMCI Over 15 Years

(A-C) Diagrams in the first row present the bidirectional transitions of MCI with associated probabilities. (D-F) Diagrams in the second row describe the transition patterns of postreversion. aMCI = amnestic MCI; MCI = mild cognitive impairment;

Figure 4. Transition Probability Curves (A) and Estimated Percentage of Total Length of Stay (B) for Postreversion Over 15 Years

Abbreviations: MCI = mild cognitive impairment;