Cognitive Trajectory Changes Over 20 Years Before Dementia Diagnosis: A Large Cohort Study

Background/Objectives Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to “normal” aging, in the trajectory of scores on a global cognitive function test—the Cognitive Abilities Screening Instrument ( CASI ). Design A prospective cohort study. Setting Community‐dwelling members of a U.S. health maintenance organization. Participants Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315). Measurements Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed with dementia, were estimated for CASI item response theory ( IRT ) scores. The impact of sex, education level, and APOE genotype on cognitive trajectories was assessed. Results Increased cognitive decline relative to “normal” aging was evident in CASI IRT at least 10 years before clinical diagnosis. Male gender, lower education, and presence of ≥1 APOE ε 4 alleles were associated with lower average IRT scores. In those who would be diagnosed with dementia, a trajectory change point was estimated at an average of 3.1 years (95% confidence interval 3.0‐3.2) before clinical diagnosis, after which cognitive decline appeared to accelerate. The change point did not differ by sex, education level, or APOE ε 4 genotype. There were subtle differences in trajectory slopes by sex and APOE ε 4 genotype, but not by education. Conclusion Decline in average global cognitive function was evident at least 10 years before clinical diagnosis of dementia. The decline accelerated about 3 years before clinical diagnosis.