The Impact of Genetic Research on our Understanding of Normal Cognitive Ageing: 1995 to 2009

Payton, Antony

doi:10.1007/s11065-009-9116-z

Cited by 87 publications

(82 citation statements)

References 231 publications

(192 reference statements)

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“…In summary, considering previous observations, together with those of the present study, the influence of KIBRA or CLSTN2 SNPs on age-related memory performance is still questionable (Payton, 2009) and difficult to interpret (Milnik et al, 2012;Schneider et al, 2010). As the first longitudinal study to investigate the effects of these SNPs on memory and hippocampal volume we did not find support that these polymorphisms influence agerelated memory decline or hippocampal atrophy over two years in our cohorts of older adults.…”

Section: Discussioncontrasting

confidence: 85%

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

et al. 2015

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure.However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145, rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65-90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippocampal volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing occasions). Overall we did not find support for an association of KIBRA either alone or in combination with CLSTN2 with memory performance or hippocampal volume, nor did variation in these genes influence longitudinal memory decline or hippocampal atrophy in two cohorts of older adults.

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Section: Discussioncontrasting

confidence: 85%

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

et al. 2015

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“…As is common in behavioral genetic studies, the effect size observed in this study was relatively small (Payton, 2009;Barnett, Jones, Robbins, & Müller, 2007). Future studies are needed to replicate these findings in independent data sets to substantiate the association between suboptimal DA modulation and forgetting.…”

Section: Discussionsupporting

confidence: 53%

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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“…Indeed, rarely do such associations account for more than 2% or 3% of the variance in the trait (Plomin, DeFries, et al, 2013). As pointed out by several authors, these low effect sizes stand in clear contrast to those of heritability estimates from twin and adoption studies, which, for general cognitive abilities, are around 50% (e.g., Harris & Deary, 2011;Hunt, 2011;Payton, 2009;Plomin, DeFries, et al, 2013;Turkheimer, 2011;Turkheimer et al, 2003). The two sets of contrasting effect sizes are at the heart of the missing-heritability problem (Maher, 2008;Turkheimer, 2011).…”

Section: Discussionmentioning

confidence: 87%

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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The Impact of Genetic Research on our Understanding of Normal Cognitive Ageing: 1995 to 2009

Cited by 87 publications

References 231 publications

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

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

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

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