APOE and BDNF Val66Met polymorphisms combine to influence episodic memory function in older adults

Ward, David; Summers, Mathew J.; Saunders, Nichole L.; Janssen, Pierce; Stuart, Kimberley E.; Vickers, James C.

doi:10.1016/j.bbr.2014.06.022

Cited by 54 publications

(47 citation statements)

References 45 publications

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“…The brain-derived neurotrophic factor (BDNF) is a protein implicated in neurogenesis and synaptic plasticity. The Val66Met polymorphism of BDNF gene is associated with decreased secretion of BDNF and has been implicated as a possible risk allele for anxiety [41] and worse cognitive functioning [42]. The Apolipoprotein E ε4 variant is the largest known genetic risk for Alzheimer’s disease and also has been implicated with anxiety [43] and stress [44].…”

Section: Discussionmentioning

confidence: 99%

Anxiety is associated with increased risk of dementia in older Swedish twins

Petkus

Reynolds

Wetherell

et al. 2015

Alzheimer's & Dementia

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INTRODUCTION We asked whether anxiety is associated with prospective risk of dementia, and the extent to which genetic influences mediate this association. METHODS Non-demented twins (n=1,082) from the Swedish Adoption Twin Study of Aging (SATSA) completed an assessment of anxiety symptoms in 1984 and were followed for 28 years. RESULTS Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up (HR = 1.04; 95% CI = 1.01–1.06). There was 48% increased risk of becoming demented for those who had experienced high anxiety at any time compared to those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic (HR = 1.11; 95% CI= 1.02–1.20) compared to monozygotic twins (HR = 1.06; 95% CI= 0.95–1.20), indicating genetic mediation. DISCUSSION Anxiety symptoms were associated with increased risk of dementia. Genetic factors common to dementia and anxiety partially mediated this association.

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Section: Discussionmentioning

confidence: 99%

Anxiety is associated with increased risk of dementia in older Swedish twins

Petkus

Reynolds

Wetherell

et al. 2015

Alzheimer's & Dementia

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“…In aging, the latter may increase BDNF expression in the brain resulting in greater synaptic plasticity (Cotman & Berchtold, 2002) and reduced cognitive impairment (Erickson et al, 2012). This augmented effect in younger and higher lifestyle activities older adult groups may then lead to large detectable differences in cognitive performance and change, particularly for those with higher genetic risk combinations (Ward et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Executive function performance and change in aging is predicted by apolipoprotein E, intensified by catechol-O-methyltransferase and brain-derived neurotrophic factor, and moderated by age and lifestyle

Sapkota

Bäckman

Dixon

2017

Neurobiology of Aging

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Recent studies have reported several genetic, health, and aging interaction effects in predicting cognitive performance and change. We used an accelerated longitudinal design to examine interactions among genetic, lifestyle, and aging for executive function (EF) in non-demented older adults (n=634; age range=53–95 years). The polymorphisms were Apolipoprotein E (APOE), Catechol-O-methyl transferase (COMT), and Brain-derived neurotrophic factor (BDNF). We tested (a) independent and additive effects of APOE, COMT, and BDNF and (b) APOE effect modification for COMT+ BDNF, on EF performance and 9-year change as separated by age and lifestyle activities. First, APOE ε4+ carriers had poorer EF performance and steeper 9-year decline. Second, APOE ε4+ carriers with (a) BDNF Met/Met genotype and (b) increasing allelic risk in the COMT+ BDNF risk panel had poorer EF performance; these effects were moderated by lifestyle activities (composite of everyday social, physical, cognitive activities). Examining APOE effect modification for COMT+ BDNF risk panel effects with other moderating factors may help identify complex neurobiological and genetic underpinnings of polygenic phenotypes such as EF in aging.

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“…As significant apolipoprotein E and BDNF interactions have been reported in normal elderly and AD patients to predict episodic memory performance [45–48], our study design may ignore the epistatic effect of the apolipoprotein E gene. However, linkage disequilibrium either from other functional polymorphisms in the BDNF gene or from another nearby gene was still possible.…”

Section: Discussionmentioning

confidence: 99%

Dose-dependent genotype effects of BDNF Val66Met polymorphism on default mode network in early stage Alzheimer's disease

et al. 2016

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In humans, brain-derived neurotrophic factor (BDNF) has been shown to play a pivotal role in neurocognition, and its gene contains a functional polymorphism (Val66Met) that may explain individual differences in brain volume and memory-related activity.In this study, we enrolled 186 Alzheimer's disease (AD) patients who underwent 3D T1 magnetic resonance imaging, and explored the gray matter (GM) structural covariance networks (SCN). The patients were divided into three groups according to their genotype: Met/Met (n = 45), Val/Met (n = 86) and Val/Val (n = 55). Seed-based analysis was performed focusing on four SCN networks. Neurobehavioral scores served as the major outcome factor.Only peak cluster volumes of default mode medial temporal lobe network showed significant genotype interactions, of which the interconnected peak clusters showed dose-dependent genotype effects. There were also significant correlations between the cognitive test scores and interconnected-cluster volumes, especially in the orbitofrontal cortex.These findings support the hypothesis that BDNF rs6265 polymorphisms modulate entorhinal cortex-interconnected clusters and the valine allele was associated with stronger structural covariance patterns that determined the cognitive outcomes.

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APOE and BDNF Val66Met polymorphisms combine to influence episodic memory function in older adults

Cited by 54 publications

References 45 publications

Anxiety is associated with increased risk of dementia in older Swedish twins

Anxiety is associated with increased risk of dementia in older Swedish twins

Executive function performance and change in aging is predicted by apolipoprotein E, intensified by catechol-O-methyltransferase and brain-derived neurotrophic factor, and moderated by age and lifestyle

Dose-dependent genotype effects of BDNF Val66Met polymorphism on default mode network in early stage Alzheimer's disease

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