Impact of APOE status on cognitive maintenance in healthy elderly persons

OBJECTIVE: The epsilon4 allele, a variant of the apolipoprotein E (ApoE) gene, is the most prominent genetic risk factor for sporadic, non-familial Alzheimer's disease (AD) currently known. We investigated the impact of the ApoE-epsilon4 status on cognitive performance at repeated test administration in elderly non-symptomatic persons, with a specific focus on practice effects. METHODS: Three hundred and fifty-five physically and mentally healthy participants of the Basel Study on the Elderly (119 F, 236 M; age 68.3 +/- 7.6; years of education 12.7 +/- 3.1; Mini-Mental State scores 29.0 +/- 1.0) were grouped into ApoE epsilon4 carriers and ApoE epsilon4 non-carriers (36.9% and 63.1% of the sample, respectively). Participants were assessed at the beginning of the longitudinal study and on average two years later by means of the California Verbal Learning Test (CVLT) and the Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB), a multidimensional cognitive test battery. Baseline and change scores were analyzed with multiple regression procedures and adjusted for age, education and gender; change scores were also adjusted for baseline performance. RESULTS: The ApoE epsilon4 non-carriers showed slightly better performance with regard to most cognitive parameters at baseline. Mean practice effects of the ApoE epsilon4 non-carriers in 12 out of 13 CVLT variables and in five out of the nine main CERAD-NAB variables were above the 50th percentile, while those of the ApoE epsilon4 carriers were below the 50th percentile in the respective distributions of test-retest change scores. CONCLUSIONS: The epsilon4 allele of the ApoE gene has a negative impact on cognitive performance, notably on episodic memory functions, in physically and mentally healthy aged persons. Practice effects seen in carriers of the ApoE epsilon4 were inferior in most areas tested to the effects seen in ApoE epsilon4 non-carriers. Further follow-up of these subjects will help to determine the clinical significance of these findings.