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. 2017 Apr:52:81-89.
doi: 10.1016/j.neurobiolaging.2016.12.022. Epub 2017 Jan 3.

Executive function performance and change in aging is predicted by apolipoprotein E, intensified by catechol-O-methyltransferase and brain-derived neurotrophic factor, and moderated by age and lifestyle

Shraddha Sapkota  1 , Lars Bäckman  2 , Roger A Dixon  3
Affiliations

Executive function performance and change in aging is predicted by apolipoprotein E, intensified by catechol-O-methyltransferase and brain-derived neurotrophic factor, and moderated by age and lifestyle

Shraddha Sapkota et al. Neurobiol Aging. 2017 Apr.

Abstract

Recent studies have reported several genetic, health, and aging interaction effects in predicting cognitive performance and change. We used an accelerated longitudinal design to examine interactions among genetic, lifestyle, and aging for executive function (EF) in non-demented older adults (n = 634; age range = 53-95 years). The polymorphisms were apolipoprotein E (APOE), catechol-O-methyltransferase (COMT), and brain-derived neurotrophic factor (BDNF). We tested (1) independent and additive effects of APOE, COMT, and BDNF and (2) APOE effect modification for COMT + BDNF, on EF performance and 9-year change as separated by age and lifestyle activities. First, APOE ε4+ carriers had poorer EF performance and steeper 9-year decline. Second, APOE ε4+ carriers with (1) BDNF Met/Met genotype and (2) increasing allelic risk in the COMT + BDNF risk panel had poorer EF performance; these effects were moderated by lifestyle activities (composite of everyday social, physical, and cognitive activities). Examining APOE effect modification for COMT + BDNF risk panel effects with other moderating factors may help identify complex neurobiological and genetic underpinnings of polygenic phenotypes such as EF in aging.

Keywords: Aging; Apolipoprotein E; Brain-derived neurotrophic factor; Catechol-O-methyltransferase; Executive function; Victoria Longitudinal Study.

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Conflict of interest statement

Disclosure Statement

All authors confirm that there is no actual or potential conflict of interest. All research has been approved continuously by relevant institutional review boards. Certificates are available and on file in the University of Alberta Research Services Office and the US National Institutes of Health. All participants have completed and signed informed consent forms.

Figures

Figure 1
Figure 1
In the young-old (YO) group, APOE ε4+ carriers performed worse at age 63 and had steeper 9-year decline in EF than their non-risk (ε4-) counterparts. In the old-old (OO) group APOE ε4+ carriers showed steeper 9-year decline on EF than their non-risk counterparts.
Figure 2
Figure 2
In the APOE ε4+ group, BDNF Met/Met homozygotes had the worst EF performance compared to their non-risk counterparts (Val homozygotes) at 75 years. In contrast, in the APOE ε4- group, BDNF genotype did not affect EF performance.
Figure 3
Figure 3
APOE effect modification was observed for COMT + BDNF additive effect on EF performance. APOE ε4+ carriers had poorer EF performance with increasing allelic risk in the COMT + BDNF risk panel at age 75 years and borderline 9-year decline. In contrast, the APOE ε4- group was protected from the deleterious effect on EF performance and decline with increasing allelic risk in the COMT + BDNF risk panel.
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