Predictors of transitions between normal cognition, cognitive impairment, and dementia in a longitudinal cohort

BackgroundUnderstanding how sociodemographic characteristics and medical history are associated with progression (or regression) of Alzheimer's disease and related dementias could inform intervention strategies, personalized prognoses, and projections of population-level burden.ObjectiveWe estimated transition rates for progression and reversion between normal cognition, cognitive impairment, dementia, and death in a longitudinal cohort, as well as associations with sociodemographic characteristics and medical history.MethodsWe applied a multistate transition model to a cohort of 960 participants (with 2-16 (median 3) annual visits; 2006-24). Covariate hazard ratios (HRs) were estimated in models adjusted for age group.ResultsSeveral covariates were associated with faster progression from normal cognition to cognitive impairment but slower progression from cognitive impairment to dementia. For example, non-Hispanic Black participants transitioned from normal to cognitive impairment at higher rates (HR: 2.29, 95% CI: 1.63, 3.21) and to dementia at lower rates (HR: 0.12, 95% CI: 0.06, 0.23) than non-Hispanic White participants. Additionally, amnestic versus non-amnestic impairment emerged as a strong predictor of transitions from cognitive impairment by reducing reversion to normal cognition (HR: 0.51, 95% CI: 0.35, 0.74) and accelerating progression to dementia (HR: 2.51, 95% CI: 1.49, 4.22). History of traumatic brain injury was associated with reversion from cognitive impairment to normal cognition (HR: 2.43, 95% CI: 1.13, 5.23).ConclusionsA better understanding and measurement of cognitive impairment is needed to explain and predict both reversion to normal cognition and why factors associated with faster onset of impairment may be associated with delayed onset of dementia.