Neuropsychological measures in normal individuals that predict subsequent cognitive decline

Objective: To examine neuropsychological measures among normal individuals that predict time to subsequent cognitive decline. Design: Cognitive performance, as measured by 6 neuropsychological tests, was examined at baseline. Participants were followed up for approximately 5 years. Cox proportional hazards models were used to evaluate the neuropsychological measures at baseline that predicted time to progression from normal cognition to mild impairment. Comparable data also examined time to progression from mild impairment to a diagnosis of Alzheimer disease. Setting: Community volunteer-based sample examined at a medical institution. Participants: One hundred and seven individuals who were cognitively normal and 235 individuals with mild cognitive impairment at baseline. Main Outcome Measures: Time to progression from normal cognition to mild impairment and time to progression from mild impairment to a diagnosis of Alzheimer disease. Results: The risk of progressing from normal to mild impairment was considerably greater among those with lower scores on tests of episodic memory (eg, hazard ratio for a 1-SD decrease in the California Verbal Learning Test, 0.55; P<.001). Normal individuals who carried at least 1 copy of the apolipoprotein E ε2 allele were less likely to develop cognitive impairments over time than individuals with no ε2 allele (hazard ratio for presence of allele, 0.13; P = .006). Measures of both episodic memory and executive function were significant predictors of time to progression from mild impairment to a clinical diagnosis of Alzheimer disease (eg, hazard ratio for a 1-SD decrease in California Verbal Learning Test score, 0.67; P =. 005; hazard ratio for a 1-SD increase in the time to complete part B of the Trail Making test, 1.40; P = .007). Among individuals with mild impairments, the apolipoprotein E ε4 allele increased risk for Alzheimer disease in a dose-dependent manner; however, this effect was not significant within the context of multivariable models. Conclusions: Episodic memory performance among normal individuals predicts time to progression to mild impairment while apolipoprotein E ε2 status is associated with lower risk of cognitive decline among normal individuals. Tests of both episodic memory and executive function are predictors of time to progression from mild impairment to a clinical diagnosis of Alzheimer disease.