Ebbinghaus Revisited: Influences of the BDNF Val<i>66</i>Met Polymorphism on Backward Serial Recall Are Modulated by Human Aging

Li, Shu-Chen; Chicherio, Christian; Nyberg, Lars; Oertzen, Timo von; Nagel, Irene E.; Papenberg, Göran; Sander, Thomas; Heekeren, Hauke R.; Lindenberger, Ulman; Bäckman, Lars

doi:10.1162/jocn.2009.21374

Cited by 60 publications

(62 citation statements)

References 67 publications

(106 reference statements)

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“…To our knowledge, this is the first evidence of interactive effects between genes related to the DA and glutamate systems on human episodic memory. Our results are in line with recent studies showing magnification of genetic effects on cognition in old age (Colzato et al, 2013;Li et al, 2010aLi et al, , 2010bLi et al, , 2013Papenberg et al, 2013). The current findings underscore the need to investigate interactive effects of multiple genes to understand interindividual differences in episodic memory in adulthood and aging.…”

Section: Discussionsupporting

confidence: 92%

Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Papenberg¹,

Li²,

Nagel³

et al. 2014

Neurobiology of Aging

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a b s t r a c tBoth the dopaminergic and glutamatergic systems modulate episodic memory consolidation. Evidence from animal studies suggests that these two neurotransmitters may interact in influencing memory performance. Given that individual differences in episodic memory are heritable, we investigated whether variations of the dopamine D2 receptor gene (rs6277, C957T) and the N-methyl-D-aspartate 3A (NR3A) gene, coding for the N-methyl-D-aspartate 3A subunit of the glutamate N-methyl-D-aspartate receptor (rs10989591, Val362Met), interactively modulate episodic memory in large samples of younger (20e31 years; n ¼ 670) and older (59e71 years; n ¼ 832) adults. We found a reliable gene-gene interaction, which was observed in older adults only: older individuals carrying genotypes associated with greater D2 and N-methyl-D-aspartate receptor efficacy showed better episodic performance. These results are in line with findings showing magnification of genetic effects on memory in old age, presumably as a consequence of reduced brain resources. Our findings underscore the need for investigating interactive effects of multiple genes to understand individual difference in episodic memory.

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Section: Discussionsupporting

confidence: 92%

Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Papenberg¹,

Li²,

Nagel³

et al. 2014

Neurobiology of Aging

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“…This study extends and investigates this phenomenon in a within-person, longitudinal framework. Our main result replicates and extends results from a number of between-person cross-sectional studies showing that Met allele carriers have lower episodic memory performance (Dempster et al, 2005;Echeverria et al, 2005;Egan et al, 2003;Hariri et al, 2003;Li et al, 2010;Miyajima et al, 2008;Tan et al, 2005), delayed recall (Miyajima et al, 2008), working memory (Echeverria et al, 2005;Rybakowski et al, 2003;Rybakowski et al, 2006), general intelligence (Tsai et al, 2004), and perceptual speed (Miyajima et al, 2008;Raz et al, 2009) compared with Val/Val homozygotes. In contrast to this earlier work, the present study examined genetic effects on individual differences in withinperson cognitive decline (by analyzing how individuals change across time as they age, rather than analyzing how individuals of different ages are different at a given time point).…”

Section: Discussionsupporting

confidence: 88%

The Val/Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene predicts decline in perceptual speed in older adults.

Ghisletta¹,

Bäckman²,

Bertram³

et al. 2014

Psychology and Aging

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The brain-derived neurotrophic factor (BDNF) promotes activity-dependent synaptic plasticity, and contributes to learning and memory. We investigated whether a common Val66Met missense polymorphism (rs6265) of the BDNF gene is associated with individual differences in cognitive decline (marked by perceptual speed) in old age. A total of 376 participants of the Berlin Aging Study, with a mean age of 83.9 years at first occasion, were assessed longitudinally up to 11 times across more than 13 years on the Digit-Letter task. Met carriers (n ϭ 123, 34%) showed steeper linear decline than Val homozygotes (n ϭ 239, 66%); the corresponding contrast explained 2.20% of the variance in change in the entire sample, and 3.41% after excluding individuals at risk for dementia. These effects were not moderated by sex or socioeconomic status. Results are consistent with the hypothesis that normal aging magnifies the effects of common genetic variation on cognitive functioning. Keywords: cognitive decline, BDNF Val/Met polymorphism, Berlin Aging StudyIn recent years, the field of cognitive aging has enriched its explanatory scope by paying increasing attention to the effects of genetic and epigenetic variation on individual differences in cognitive performance. Two broad approaches can be distinguished

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“…Using tasks assessing spatial working memory and executive functioning, Nagel et al (2008) found that the effects of variation in the catechol-O-methyltransferase and brain-derived neurotrophic factor (BDNF) genes among older adults are magnified relative to younger adults: Carrying disadvantageous alleles of both genes resulted in poorer cognitive performance for older adults but not for the younger adults. Li, Chicherio, et al (2010) investigated the effects of the BDNF gene and obtained an identical pattern of data in backward serial recall. Relatedly, an interactive effect of DAT (DAT1) and D2 receptor (DRD2) genotypes on backward serial recall was found to be larger in older than in younger adults (Li et al, 2013).…”

Section: Magnification Of Genetic Effects In Old Agementioning

confidence: 99%

Dopaminergic Gene Polymorphisms Affect Long-term Forgetting in Old Age: Further Support for the Magnification Hypothesis

Papenberg

Bäckman

Nagel

et al. 2013

Journal of Cognitive Neuroscience

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Abstract■ Emerging evidence from animal studies suggests that suboptimal dopamine (DA) modulation may be associated with increased forgetting of episodic information. Extending these observations, we investigated the influence of DA-relevant genes on forgetting in samples of younger (n = 433, 20-31 years) and older (n = 690, 59-71 years) adults. The effects of single nucleotide polymorphisms of the DA D2 (DRD2) and D3 (DRD3) receptor genes as well as the DA transporter gene (DAT1; SLC6A3) were examined. Over the course of one week, older adults carrying two or three genotypes associated with higher DA signaling (i.e., higher availability of DA and DA receptors) forgot less pictorial information than older individuals carrying only one or no beneficial genotype. No such genetic effects were found in younger adults. The results are consistent with the view that genetic effects on cognition are magnified in old age. To the best of our knowledge, this is the first report to relate genotypes associated with suboptimal DA modulation to more long-term forgetting in humans. Independent replication studies in other populations are needed to confirm the observed association. ■

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Ebbinghaus Revisited: Influences of the BDNF Val66Met Polymorphism on Backward Serial Recall Are Modulated by Human Aging

Cited by 60 publications

References 67 publications

Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Dopamine and glutamate receptor genes interactively influence episodic memory in old age

The Val/Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene predicts decline in perceptual speed in older adults.

Dopaminergic Gene Polymorphisms Affect Long-term Forgetting in Old Age: Further Support for the Magnification Hypothesis

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