The genetic risk variant APOE ε4 predicts cognitive aging and dementia risk yet its role in early life cognitive growth and functioning is not understood. We assessed the possible association of APOE genotypes and cognitive performance from mid-childhood to mid-adulthood in the ongoing Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife) study, with three to four decades of participant data available from two foundational studies, the Colorado Adoption Project (CAP) and Longitudinal Twin Study (LTS). APOE ε4 was a significant predictor of lower Full-Scale, Performance, and Verbal IQ scores, compared to ε33 individuals, in longitudinal analyses from the year 7-, 12- and 16-year assessments (7 to 18 years; N=1321). Results suggested Full scale IQ scores were lower for each ε4 allele, compared to APOE ε33 (adjusted p < 0.01). Moreover, the ε4 effects for Full-scale IQ were more evident in females (adjusted p < 0.02) compared to males. Consistent effects were observed for Verbal and Performance IQ.
Up to eight assessments between 9 and 46 years (N= 1380) were available for two episodic memory tasks (Names and Faces, Picture Memory), and a general cognitive ability (GCA) factor formed from the Colorado Perceptual Speed (CPS), ETS Card Rotations, the Wechsler Similarities subtest, and the paired-associates Names and Faces measures. Nonlinear logistic growth models were fitted to explore individual differences in the amount of gain to the upper performance asymptote, age at maximum acceleration at inflection point, and rate of change. Initial results did not suggest differential growth by APOE for memory or a general cognitive ability (GCA) factor that was dominated by processing speed. Although results of these initial analyses suggest that APOE ε4 genotypes may not influence growth patterns, they may be associated with lower cognitive ability as early as middle childhood, particularly for Performance and Full-scale IQ and to a lesser extent for Verbal IQ. APOE may show stronger effects on performance and full-scale IQ in women than men, consistent with emerging evidence of a differential risk of Mild Cognitive Impairment and Alzheimer’s disease.
Supported by NIH Grant No. R01AG046938
Aging , Cognition: Education, Intelligence, Memory, Attention , Development
