Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms.
Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms.
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DOI：
10.3389/neuro.09.011.2008
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发表时间：
2008
影响因子：
2.9
通讯作者：
Kramer AF
中科院分区：
文献类型：
--
作者：
Erickson KI;Kim JS;Suever BL;Voss MW;Francis BM;Kramer AF
多巴胺能和神经营养系统的遗传变异可能导致与年龄相关的执行控制和记忆功能障碍。在这项研究中，我们研究了儿茶酚- o -甲基转移酶（COMT）和脑源性神经营养因子（BDNF）的遗传多态性是否与老年人在10年期间发生的认知能力下降的轨迹有关。COMT （Val158/108Met）基因的单核苷酸多态性影响前额皮质多巴胺的浓度。此外，BDNF亲结构域Val/Met的替换（Val66Met）会影响BDNF分泌和运输的调节，Met携带者表现出分泌减少和认知功能下降。我们发现，在任务转换范式的10年跨度中，损伤并没有作为COMT多态性的函数而变化。然而，对于BDNF多态性，Met携带者在第一次测试中表现不如Val纯合子，但在10年的时间里，只有Val纯合子表现出显著的性能下降。我们的研究结果表明，COMT多态性不影响与年龄相关的执行控制能力下降的轨迹，而BDNF的Val/Val多态性可能会促进老年认知衰退的更快速度。这些结果讨论了BDNF在衰老中的作用以及Met等位基因对老年认知功能的转化影响。
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.
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DOI：
10.1073/pnas.111134598
发表时间：
2001-06-05
影响因子：
11.1
作者：
Egan, MF;Goldberg, TE;Weinberger, DR
通讯作者：
Weinberger, DR
影响因子：
10.6
作者：
Bruder, GE;Keilp, JG;Gilliam, TC
通讯作者：
Gilliam, TC
影响因子：
10.6
作者：
Barnett, Jennifer H.;Scoriels, Linda;Munafo, Marcus R.
通讯作者：
Munafo, Marcus R.
影响因子：
2.6
作者：
de Frias, CM;Annerbrink, K;Nilsson, LG
通讯作者：
Nilsson, LG
影响因子：
5.3
作者：
Hariri, AR;Goldberg, TE;Weinberger, DR
通讯作者：
Weinberger, DR