APOE ε4 and cognitive function in early life: A meta-analysis.

Abstract

Introduction. It is well established that the Apolipoprotein E (APOE) ε4 allele is associated with cognitive impairment and Alzheimer's disease in old age. By contrast, several studies have demonstrated cognitive benefits in young ε4 carriers. It is therefore possible that the ε4 allele exhibits a pleiotropic association with cognition across the lifespan where ε4-related benefits in youth reverse in later life to become risk factors for cognitive impairment and dementia in later life. To date though, there has been no broad quantitative review of work assessing APOE-cognition associations in children, adolescents and young adults.Methods. Based on 20 studies investigating cognitive performance in ε4 carrying young persons and their non-ε4 counterparts, a meta-analytic study was conducted to examine APOE ε 4-related differences in cognitive performance. Additionally, we assessed whether the level of executive demands affected the strength of association between the ε4 allele and cognitive measure.Results. In all analyses, estimated APOE ε4 related population effect sizes did not reliably differ from zero. Furthermore, the level of executive demands of the task did not affect this finding. Conclusion.We found no APOE ε4-related cognitive benefits in young adults, adolescents, and children and findings were not moderated by the level of executive demands in a cognitive task. Given the current empirical evidence therefore, suggestions that APOE ε4 exhibits a pleiotropic association with cognition across the lifespan should be treated with caution.Key words: Apolipoprotein E; APOE; cognition; cognitive performance; executive processes; young adults; adolescence; childhood; meta-analysis 3 Apolipoprotein E (APOE) is a protein that plays an important role in cholesterol transportation (for reviews of the mechanisms and functions of APOE in the nervous system, see Czyzewski, Pfeffer, & Barcikowska, 1998; Harris et al., 2003;Lahiri, Sambamurti, & Bennett, 2004;Mahley, 1988;Menzel, Kladetzky, & Assmann, 1983;Rocchi, Pellegrini, Siciliano, & Murri, 2003;Rubinsztein, 1995). The gene coding for APOE is located on chromosome 19 and has three alleles, ɛ2, ɛ3, and ɛ4.APOE ɛ4 is well established as a risk factor for Alzheimer's disease (AD: Corder et al., 1993; Saunders et al, 1993), where persons possessing the ɛ4 allele have a three to four times higher risk for developing AD (see also Farrer et al., 1997, for a meta-analysis on effects of age, sex, and ethnicity on the association between APOE genotype and AD).Moreover, various studies have found that APOE ɛ4 is strongly associated with cognitive decline among persons who have been diagnosed with AD (e.g., Hirono, Hashimoto, Yasuda, Kazui, & Mori, 2003;Marra et al., 2004;Martins, Oulhaj, De Jager, & Williams, 2005;Plassman & Breitner, 1996). In addition, more than a decade of research has also demonstrated deficits in various cognitive domains in non-demented ɛ4 carriers in comparison with non-ɛ4 carriers in middle and old adulthood (e.g., Berr et al., 1996;Cantu, ...

Apolipoprotein E ε4 Allele Modulates the Immediate Impact of Acute Exercise on Prefrontal Function

“…This finding supports the existence of some form of cognitive benefit for young Ɛ4 carriers. It is still undetermined whether carrying one copy of the Ɛ4 allele is beneficial or not at a young age (Han & Bondi, 2008;Ihle et al, 2012), but we propose that our findings are consistent with the idea of antagonistic pleiotropy (Han & Bondi, 2008;Tuminello & Han, 2011), as young carriers in our sample showed a computational advantage. The neural mechanisms supporting the pleiotropic effects of the Ɛ4 allele, however, are still undetermined.…”

Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging

“…Thus, this study suggests better memory and neural efficiency in young ε4 carriers. However, a recent meta-analysis did not find any support for these patterns (Ihle et al 2012). Also, two other fMRI studies reported increased BOLD responses in the MTL in ε4 carriers relative to non-carriers during scene and visual object encoding tasks, in the absence of performance differences (Dennis et al 2010;Filippini et al 2009).…”

Apolipoprotein E ( ApoE ) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

“…However, a recent meta-analysis of 20 studies shows that the ApoE4 allele is not associated with statistically significant cognitive benefits in young adults, adolescents or children. Thus, the pleiotropic effect of ApoE4 in cognitive abilities across the lifespan has not been proved [25].…”

“…It may be related to better development of the cognitive function [18,19], protection against infectious diseases [20 -23] or to reproductive advantage [24], but the results of studies conducted in all these areas have been inconclusive [9,25,26]. We suggest that the ApoE4 allele has persisted in the human population because it significantly increases reproductive potential in women.…”