Abstract

AbstractBackgroundThe natural trajectory of reversion from MCI to normal cognition (NC) and the cognitive pattern post‐reversion have been poorly explored in the existing literature. The main goals of this study were as follows: (1) to quantitatively predict bidirectional transitions of MCI (reversion to NC and progression to dementia); (2) to explore patterns of future cognitive changes post‐reversion; and (3) to estimate the effects of selected covariates on transition probabilities in the course of cognitive loss.MethodThe National Alzheimer’s Coordinating Center database was funded by a National Institute on Aging/National Institutes of Health grant (U24 AG072122). Data for this study comprised 24,220 observations from 6,651 participants with an MCI diagnosis at study entry during at least two visits between June 2005 and February 2021. Defining NC and MCI as transient states and dementia as an absorbing state, we explored the fate of MCI and future cognitive changes post‐reversion using the continuous‐time, multi‐state Markov model, which provides information on the transition probability between multiple states, hazard ratio, mean sojourn time, and total length of stay over 15 years.ResultTransition intensity of re‐progression to MCI for post‐reversion was 0.3168, 2.48 times greater than the progression from MCI to dementia or reversion from MCI to NC. For the post‐reversion participants, the chance of progressing to dementia increased by 2% per year. participants who re‐progressed to MCI had an approximately 40% probability of reversing to NC again over the 15‐year period. participants stayed in the post‐reversion NC state for 3.2667 years (range 2.9349–3.6360) and in the MCI state for 1.7605 years (range 1.5134–2.0480) before progressing to dementia. Age, cognitive function, daily activity ability, and depressive symptoms were significant predictors of progression to dementia.ConclusionThere were distinct transition dynamics between amnesic MCI (aMCI) and nonamnesic (naMCI). The post‐reversion participants remained at increased risk of re‐progression to MCI or progression to dementia in the long term. Findings in this study can serve as valuable references for relevant research and healthcare professionals to help understand the natural history of cognitive loss and create proactive plans and targeted interventions.

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