P1‐011: Cognitive Resilience Predicts Reverse Transitions from Mild Cognitive Impairment to Normal Cognition: Findings from the Nun Study

Mild cognitive impairment is associated with an increased risk of progressing to dementia. Although reversion to normal cognition has also been observed, it is not well characterized. Our objective was to assess the effect of age, apolipoprotein E-ε4 (APOE-ε4), and indicators of cognitive resilience (early-life intellectual factors) on the transition from mild cognitive impairment to normal cognition. Analyses were based on data from the Nun Study, a longitudinal study of aging and dementia in 678 religious sisters aged 75+ years living in the United States. Cognitive status and mortality were determined in a cohort of 613 participants with up to 12 annual cognitive assessments. A multi-state Markov model was used to study the risk of transitions among four states: normal cognition, mild cognitive impairment, dementia and death. The transition risks were allowed to depend on age (5-year age groups), APOE-ε4, and early-life intellectual factors including educational attainment, academic performance in high school (first-year English, algebra, or geometry), and written language skills (idea density, grammatical complexity). Each five-year increase in age was associated with a reduced chance of reversion to normal cognition, but this reached significance only for those 90-95 years (90-95 vs. 75-80 age groups: hazard ratio [HR]=0.37; 95% confidence interval [CI]=0.19-0.74). In transition models including age, APOE and education, APOE-ε4 carriers (1+ alleles) had a significantly lower chance of reversion than noncarriers (HR=0.37; 95% CI=0.22-0.62), whereas more highly educated participants had a significantly higher chance of reversion (Masters degree or higher vs. high school or lower: HR=2.43; 95% CI=1.13-5.20). Participants with higher academic performance in English (>=90% vs <90%: HR=1.58; 95% CI=1.09-2.30) and higher idea density (Quartile [Q] 3-4 vs Q1-2: HR=2.39; 95% CI=1.39-4.10) or grammatical complexity (Q2-4 vs Q1: HR=3.55; 95% CI=1.08-11.69) had significantly higher chances of reversion in models adjusted for age, APOE and education. Although a diagnosis of mild cognitive impairment has been associated with an increased risk of progressing to dementia, indicators of cognitive resilience may predict reversion from this state to normal cognition. Predictors of these reverse transitions could inform strategies to prevent or postpone transitions to cognitive impairment and dementia.