APOE epsilon 4 differentially influences change in memory performance depending on age. The SMART-MR study

作者：Jochemsen Hadassa M; Muller Majon; van der Graaf Yolanda; Geerlings Mirjam I^*

来源：Neurobiology of Aging, 2012, 33(4): 832.e15.

DOI：10.1016/j.neurobiolaging.2011.07.016

• Antagonistic pleiotropy
• Cognition
• Memory performance
• APOE epsilon 4 allele
• Age
• Cohort

The apolipoprotein E (APOE) gene may act differently in young and old persons, known as antagonistic pleiotropy. We therefore examined the prospective associations between the APOE epsilon 4 allele and cognitive functioning, and the modifying effect of age, in 375 nondemented adults (mean age 57 +/- 10 years; follow-up period 3.8 +/- 0.2 years) with available data on APOE genotype and cognitive functioning, within the SMART-MR (Second Manifestations of ARTerial disease-Magnetic Resonance) cohort study. Neuropsychological tests assessing memory performance and executive functioning were performed at baseline and follow-up, and composite z-scores were calculated. Age significantly modified the association of APOE epsilon 4 with change in memory performance (p interaction = 0.02). In persons %26lt;= 57 years (median split), an APOE epsilon 4 allele was associated with an increase in immediate recall (B = 0.42; 95% confidence interval [CI], 0.17 to 0.66) and delayed recall (B = 0.37; 95% CI, 0.09 to 0.64), while in persons %26gt; 57 years, an APOE epsilon 4 allele was associated with decline in immediate recall (B = -0.25; 95% CI, -0.52 to 0.01). Our findings suggest that the APOE epsilon 4 allele has a differential effect on change in verbal memory performance depending on age, consistent with the hypothesis of antagonistic pleiotropy.

• 出版日期2012-4