INTERACTION BETWEEN AGE AND APOE GENOTYPE ON THE COGNITIVE PERFORMANCE OF HEALTHY INDIVIDUALS AT RISK FOR ALZHEIMER’S DISEASE

Abstract

The ε4 allele of APOE gene is a strong genetic risk factor for sporadic Alzheimer disease (AD). Cognitive performance in healthy adults is influenced by age and other sociodemographic factors. To identify asymptomatic individuals at higher risk of memory impairment is critical for prevention and intervention studies. The aim of our study is to assess the relationship between cognitive performance, APOE genotype and age in healthy individuals at risk for AD. The ALFA (for Alzheimer and Families) study is a prospective cohort of 2,743 cognitively healthy subjects, aged 45 to 74, many of them AD patients’ descendants. Anthropometric, sociodemographic and epidemiological characteristics are available for participants. Episodic memory measured by means of the Memory Binding Test, as well as executive and reasoning functions assessed by WAIS-IV subtests, were administered to evaluate participants’ cognitive performance. General lineal models were conducted to assess the association between cognitive performance and age in a cross-sectional analysis. Stratified analyses by APOE genotypes were performed. Gender and cognitive reserve were included in the models as potential confounders. Amongst the 2,642 participants with complete information, our population includes 915 APOE-ε4 allele carriers (86 of those are APOE-ε4/ε4 homozygotes). As expected, we observed a negative association between cognitive performance and age: the older the participants, the lower their performance in all tests. This association was stronger in APOE-ε4 allele carriers than non-carriers (p-interaction<0.05). Surprisingly, the association between episodic memory and age was weaker for APOE-ε4/ε4 compared to non-carriers. This interaction was not seen when executive and reasoning functions were assessed: there were no differences in the association between performance and participant's age among genotype groups. To rule out a potential selection bias due to strict inclusion criteria in relation to participant's cognition status, findings will be replicated in independent cohorts. In a population-based cohort of cognitively healthy individuals at risk for AD, age and APOE-ε4 allele influence episodic memory performance. The paradoxical performance observed in APOE-ε4/ε4 may be in favor of the early neurotropic role of APOE, which is followed by a detrimental effect related with AD risk.