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The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function.

Ward DD, Summers MJ, Saunders NL, Ritchie K, Summers JJ, Vickers JC - Transl Psychiatry (2015)

Bottom Line: CR accounted for 8.5% of the variance in executive function in BDNF Val homozygotes, but CR was a nonsignificant predictor in BDNF Met carriers.APOE polymorphisms were not linked to the influence of CR on cognitive function.This result implicates BDNF in having an important role in capacity for building or accessing CR.

View Article: PubMed Central - PubMed

Affiliation: 1] School of Medicine, University of Tasmania, Hobart, TAS, Australia [2] Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, TAS, Australia.

ABSTRACT
The concept of cognitive reserve (CR) has been proposed to account for observed discrepancies between pathology and its clinical manifestation due to underlying differences in brain structure and function. In 433 healthy older adults participating in the Tasmanian Healthy Brain Project, we investigated whether common polymorphic variations in apolipoprotein E (APOE) or brain-derived neurotrophic factor (BDNF) influenced the association between CR contributors and cognitive function in older adults. We show that BDNF Val66Met moderates the association between CR and executive function. CR accounted for 8.5% of the variance in executive function in BDNF Val homozygotes, but CR was a nonsignificant predictor in BDNF Met carriers. APOE polymorphisms were not linked to the influence of CR on cognitive function. This result implicates BDNF in having an important role in capacity for building or accessing CR.

No MeSH data available.


BDNF Val66Met moderates the relationship between CR and executive function scores. The plot represents age- and gender-adjusted executive function performance as predicted by the composite CR proxy variable for those with low CR (CR scores less than the mean–1s.d.) and high CR (CR scores greater than the mean+1s.d.) for BDNF Met carriers and Val homozygotes, separately. BDNF, brain-derived neurotrophic factor; CR, cognitive reserve.
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fig1: BDNF Val66Met moderates the relationship between CR and executive function scores. The plot represents age- and gender-adjusted executive function performance as predicted by the composite CR proxy variable for those with low CR (CR scores less than the mean–1s.d.) and high CR (CR scores greater than the mean+1s.d.) for BDNF Met carriers and Val homozygotes, separately. BDNF, brain-derived neurotrophic factor; CR, cognitive reserve.

Mentions: We then assessed whether the inclusion of APOE/BDNF Val66Met allelic carrier data significantly improved the fit of the models. Notably, no significant main effects of genetic predictors, APOE or BDNF Val66Met, were identified for any cognitive domain. A moderation analysis (PROCESS) was then conducted examining whether the inclusion of CR × APOE or CR × BDNF interaction terms significantly improved the fit of regression models. Results indicated that a single genetically based moderation effect on CR was present (Table 3). Specifically, inclusion of the CR × BDNF Val66Met interaction term led to a significant increase in the amount of variance in executive function explained by the model (ΔR2=0.01, P=0.05). Simple slopes analysis was conducted in order to determine the basis of the moderation effect of BDNF polymorphism on the conditional effect between CR and executive function, and to determine whether the slopes statistically differed from zero for BDNF Met carriers and noncarriers, separately. These analyses indicate that a significant positive relationship between CR and executive function was identified in BDNF Val homozygotes (β=0.13, t=5.56, s.e.=0.02, P<0.01), but was not evident in BDNF Met carriers (β=0.05, t=1.52, s.e.=0.03, P=0.13). In BDNF Val homozygotes, CR accounted for a significant 8.6% of variance in executive function performance. In BDNF Met carriers, CR accounted for a nonsignificant 1.5% of variance in executive function performance. Simple slopes are presented in Figure 1.


The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function.

Ward DD, Summers MJ, Saunders NL, Ritchie K, Summers JJ, Vickers JC - Transl Psychiatry (2015)

BDNF Val66Met moderates the relationship between CR and executive function scores. The plot represents age- and gender-adjusted executive function performance as predicted by the composite CR proxy variable for those with low CR (CR scores less than the mean–1s.d.) and high CR (CR scores greater than the mean+1s.d.) for BDNF Met carriers and Val homozygotes, separately. BDNF, brain-derived neurotrophic factor; CR, cognitive reserve.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490292&req=5

fig1: BDNF Val66Met moderates the relationship between CR and executive function scores. The plot represents age- and gender-adjusted executive function performance as predicted by the composite CR proxy variable for those with low CR (CR scores less than the mean–1s.d.) and high CR (CR scores greater than the mean+1s.d.) for BDNF Met carriers and Val homozygotes, separately. BDNF, brain-derived neurotrophic factor; CR, cognitive reserve.
Mentions: We then assessed whether the inclusion of APOE/BDNF Val66Met allelic carrier data significantly improved the fit of the models. Notably, no significant main effects of genetic predictors, APOE or BDNF Val66Met, were identified for any cognitive domain. A moderation analysis (PROCESS) was then conducted examining whether the inclusion of CR × APOE or CR × BDNF interaction terms significantly improved the fit of regression models. Results indicated that a single genetically based moderation effect on CR was present (Table 3). Specifically, inclusion of the CR × BDNF Val66Met interaction term led to a significant increase in the amount of variance in executive function explained by the model (ΔR2=0.01, P=0.05). Simple slopes analysis was conducted in order to determine the basis of the moderation effect of BDNF polymorphism on the conditional effect between CR and executive function, and to determine whether the slopes statistically differed from zero for BDNF Met carriers and noncarriers, separately. These analyses indicate that a significant positive relationship between CR and executive function was identified in BDNF Val homozygotes (β=0.13, t=5.56, s.e.=0.02, P<0.01), but was not evident in BDNF Met carriers (β=0.05, t=1.52, s.e.=0.03, P=0.13). In BDNF Val homozygotes, CR accounted for a significant 8.6% of variance in executive function performance. In BDNF Met carriers, CR accounted for a nonsignificant 1.5% of variance in executive function performance. Simple slopes are presented in Figure 1.

Bottom Line: CR accounted for 8.5% of the variance in executive function in BDNF Val homozygotes, but CR was a nonsignificant predictor in BDNF Met carriers.APOE polymorphisms were not linked to the influence of CR on cognitive function.This result implicates BDNF in having an important role in capacity for building or accessing CR.

View Article: PubMed Central - PubMed

Affiliation: 1] School of Medicine, University of Tasmania, Hobart, TAS, Australia [2] Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, TAS, Australia.

ABSTRACT
The concept of cognitive reserve (CR) has been proposed to account for observed discrepancies between pathology and its clinical manifestation due to underlying differences in brain structure and function. In 433 healthy older adults participating in the Tasmanian Healthy Brain Project, we investigated whether common polymorphic variations in apolipoprotein E (APOE) or brain-derived neurotrophic factor (BDNF) influenced the association between CR contributors and cognitive function in older adults. We show that BDNF Val66Met moderates the association between CR and executive function. CR accounted for 8.5% of the variance in executive function in BDNF Val homozygotes, but CR was a nonsignificant predictor in BDNF Met carriers. APOE polymorphisms were not linked to the influence of CR on cognitive function. This result implicates BDNF in having an important role in capacity for building or accessing CR.

No MeSH data available.