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Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms.

Erickson KI, Kim JS, Suever BL, Voss MW, Francis BM, Kramer AF - Front Hum Neurosci (2008)

Bottom Line: We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism.However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span.Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age.

View Article: PubMed Central - PubMed

Affiliation: Psychology Department, University of Illinois at Urbana-Champaign Champaign, IL 61801, USA. kiericks@uiuc.edu

ABSTRACT
Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.

No MeSH data available.


Related in: MedlinePlus

Results from the task-switching paradigm as a function of the BDNF polymorphism and Time for each condition. Only the Val/Val homozygotes experienced a decline in performance for both the repeat and switch conditions, whereas the Val/Met carriers showed no decline over the 10-year span.
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Figure 2: Results from the task-switching paradigm as a function of the BDNF polymorphism and Time for each condition. Only the Val/Val homozygotes experienced a decline in performance for both the repeat and switch conditions, whereas the Val/Met carriers showed no decline over the 10-year span.

Mentions: For BDNF, we found that main effects of Time [F(1,44) = 2.13; n.s.] and Genotype [F(1,44) = 0.09; n.s.] were not significant (Table 2). However, consistent with the view that the Met allele might provide some protection in old age or that the Val homozygotes might experience greater decline with advancing age, we found a significant Time × Genotype interaction [F(1,44) = 7.54; p < 0.009; η2p = 0.15] on RTs in the task-switching paradigm such that the Val homozygotes experienced a significantly greater decline in performance over the 10-year period compared to the Met carriers (see Figure 2). There was also a trend for a Time × Genotype × Condition interaction [F(1,44) = 3.15; p < 0.08; η2p = 0.07] such that Val carriers experienced a greater decline in performance for the switch condition compared with the repeat condition over the 10-year span compared to the Met carriers. This trend was confirmed by examining switch cost (switch RT – repeat RT). For the accuracy measures, neither the Time × Genotype interaction or the Time × Genotype × Condition interaction reached significance indicating that unlike the RTs, the accuracy rates were not influenced by the BDNF polymorphism. However, we found a significant Genotype × Condition interaction on the accuracy rates [F(1,44) = 4.94; p < 0.03; η2p = 0.10] with the Val homozygotes performing better than the heterozygotes on the repeat condition compared to the switch condition.


Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms.

Erickson KI, Kim JS, Suever BL, Voss MW, Francis BM, Kramer AF - Front Hum Neurosci (2008)

Results from the task-switching paradigm as a function of the BDNF polymorphism and Time for each condition. Only the Val/Val homozygotes experienced a decline in performance for both the repeat and switch conditions, whereas the Val/Met carriers showed no decline over the 10-year span.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2572207&req=5

Figure 2: Results from the task-switching paradigm as a function of the BDNF polymorphism and Time for each condition. Only the Val/Val homozygotes experienced a decline in performance for both the repeat and switch conditions, whereas the Val/Met carriers showed no decline over the 10-year span.
Mentions: For BDNF, we found that main effects of Time [F(1,44) = 2.13; n.s.] and Genotype [F(1,44) = 0.09; n.s.] were not significant (Table 2). However, consistent with the view that the Met allele might provide some protection in old age or that the Val homozygotes might experience greater decline with advancing age, we found a significant Time × Genotype interaction [F(1,44) = 7.54; p < 0.009; η2p = 0.15] on RTs in the task-switching paradigm such that the Val homozygotes experienced a significantly greater decline in performance over the 10-year period compared to the Met carriers (see Figure 2). There was also a trend for a Time × Genotype × Condition interaction [F(1,44) = 3.15; p < 0.08; η2p = 0.07] such that Val carriers experienced a greater decline in performance for the switch condition compared with the repeat condition over the 10-year span compared to the Met carriers. This trend was confirmed by examining switch cost (switch RT – repeat RT). For the accuracy measures, neither the Time × Genotype interaction or the Time × Genotype × Condition interaction reached significance indicating that unlike the RTs, the accuracy rates were not influenced by the BDNF polymorphism. However, we found a significant Genotype × Condition interaction on the accuracy rates [F(1,44) = 4.94; p < 0.03; η2p = 0.10] with the Val homozygotes performing better than the heterozygotes on the repeat condition compared to the switch condition.

Bottom Line: We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism.However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span.Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age.

View Article: PubMed Central - PubMed

Affiliation: Psychology Department, University of Illinois at Urbana-Champaign Champaign, IL 61801, USA. kiericks@uiuc.edu

ABSTRACT
Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.

No MeSH data available.


Related in: MedlinePlus