Apolipoprotein E genotype and memory in the sixth decade of life

Schultz, Mark; Lyons, Michael J.; Franz, Carol E.; Grant, Michael D.; Boake, Corwin; Jacobson, Kristen C.; Xian, Hong; Schellenberg, Gerard D.; Eisen, Seth A.; Kremen, William S.

doi:10.1212/01.wnl.0000286941.74372.cc

Cited by 52 publications

(63 citation statements)

References 42 publications

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“…Overall, individual effect sizes ranged from -.25 to .64. Only one of the 26 studylevel effect sizes was reliably greater than zero (i.e., Schultz et al, 2008 Figure 2. Again, it can be seen that with increasing sample size, respective…”

Section: High and Low Executive Tasksmentioning

confidence: 99%

“…None of the study-level effect sizes for the high executive subgroup was reliably greater than zero. However, one of the effect sizes for the low executive tasks (i.e., Schultz et al, 2008) All of the foregoing analyses were rerun having excluded the fMRI studies as in such studies experimental groups usually are matched on several variables (e.g., cognitive performance) to disentangle neuronal differences (i.e. this is a less conservative approach of the present meta-analysis).…”

Section: High and Low Executive Tasksmentioning

confidence: 99%

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APOE ε4 and cognitive function in early life: A meta-analysis.

Ihle¹,

Bunce²,

Kliegel³

2012

Neuropsychology

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Introduction. It is well established that the Apolipoprotein E (APOE) ε4 allele is associated with cognitive impairment and Alzheimer's disease in old age. By contrast, several studies have demonstrated cognitive benefits in young ε4 carriers. It is therefore possible that the ε4 allele exhibits a pleiotropic association with cognition across the lifespan where ε4-related benefits in youth reverse in later life to become risk factors for cognitive impairment and dementia in later life. To date though, there has been no broad quantitative review of work assessing APOE-cognition associations in children, adolescents and young adults.Methods. Based on 20 studies investigating cognitive performance in ε4 carrying young persons and their non-ε4 counterparts, a meta-analytic study was conducted to examine APOE ε 4-related differences in cognitive performance. Additionally, we assessed whether the level of executive demands affected the strength of association between the ε4 allele and cognitive measure.Results. In all analyses, estimated APOE ε4 related population effect sizes did not reliably differ from zero. Furthermore, the level of executive demands of the task did not affect this finding. Conclusion.We found no APOE ε4-related cognitive benefits in young adults, adolescents, and children and findings were not moderated by the level of executive demands in a cognitive task. Given the current empirical evidence therefore, suggestions that APOE ε4 exhibits a pleiotropic association with cognition across the lifespan should be treated with caution.Key words: Apolipoprotein E; APOE; cognition; cognitive performance; executive processes; young adults; adolescence; childhood; meta-analysis 3 Apolipoprotein E (APOE) is a protein that plays an important role in cholesterol transportation (for reviews of the mechanisms and functions of APOE in the nervous system, see Czyzewski, Pfeffer, & Barcikowska, 1998; Harris et al., 2003;Lahiri, Sambamurti, & Bennett, 2004;Mahley, 1988;Menzel, Kladetzky, & Assmann, 1983;Rocchi, Pellegrini, Siciliano, & Murri, 2003;Rubinsztein, 1995). The gene coding for APOE is located on chromosome 19 and has three alleles, ɛ2, ɛ3, and ɛ4.APOE ɛ4 is well established as a risk factor for Alzheimer's disease (AD: Corder et al., 1993; Saunders et al, 1993), where persons possessing the ɛ4 allele have a three to four times higher risk for developing AD (see also Farrer et al., 1997, for a meta-analysis on effects of age, sex, and ethnicity on the association between APOE genotype and AD).Moreover, various studies have found that APOE ɛ4 is strongly associated with cognitive decline among persons who have been diagnosed with AD (e.g., Hirono, Hashimoto, Yasuda, Kazui, & Mori, 2003;Marra et al., 2004;Martins, Oulhaj, De Jager, & Williams, 2005;Plassman & Breitner, 1996). In addition, more than a decade of research has also demonstrated deficits in various cognitive domains in non-demented ɛ4 carriers in comparison with non-ɛ4 carriers in middle and old adulthood (e.g., Berr et al., 1996;Cantu, ...

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Section: High and Low Executive Tasksmentioning

confidence: 99%

Section: High and Low Executive Tasksmentioning

confidence: 99%

APOE ε4 and cognitive function in early life: A meta-analysis.

Ihle¹,

Bunce²,

Kliegel³

2012

Neuropsychology

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“…Schultz et al (2008) compared the cognitive test performance of army cadets in the 6 th decade of life, to their scores on the same measure at age 20, and found ε4+…”

Section: Longitudinal Assessmentsmentioning

confidence: 99%

“…This led to the hypothesis that ε4+ may show cognitive advantages earlier in life, with performance advantages similarly being demonstrated in some (Alexander et al, 2007;Han et al, 2007;Schultz et al, 2008), although not all (Bunce et al, 2014;Bunce, Anstey, Burns, Christensen, & Easteal, 2011;Jorm et al, 2007) studies assessing genotype differences with neuropsychological batteries. Importantly, no steps have been taken to explore the potential moderating effects of early-life IQ and education on the trajectory of cognitive ageing in ε4+ through longitudinal research.…”

Section: Introductionmentioning

confidence: 99%

The Elusive Nature of APOE ε4 in Mid-adulthood: Understanding the Cognitive Profile

Lancaster

Tabet

Rusted

2017

J Int Neuropsychol Soc

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Objective: The APOE ε4 allele is an established risk factor for dementia, yet this genetic variant is associated with a mixed cognitive profile across the lifespan. This paper undertakes both a systematic and meta-analytic review of research investigating APOE-related differences in cognition in mid-adulthood, when detrimental effects of the allele may first be detectable.Method: 36 papers investigating the behavioural effects of APOE ε4 in mid-adulthood (defined as a mean sample age between 35-60 years) were reviewed. In addition, the effect of carrying an ε4 allele on individual cognitive domains was assessed in separate meta-analyses. Results:The average effect size of APOE ε4 status was non-significant across cognitive domains. Further consideration of genotype effects indicates preclinical effects of APOE ε4 may be observable in memory and executive functioning. Conclusions:The cognitive profile of APOE ε4 carriers at mid-age remains elusive. Whilst there is support for comparable performance by ε4 and non-e4 carriers in the 5 th decade, studies administering sensitive cognitive paradigms indicate a more nuanced profile of cognitive differences. Methodological issues in this field preclude strong conclusions, which future research must address, as well as considering the influence of further vulnerability factors on genotype effects.

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“…To date, reported effects of APOE e4 in mid-adulthood are inconsistent (for review; Lancaster et al, under review;Rusted & Carare, 2015;Salvato, 2015), with many studies reporting null effects. The exceptions are studies within the domain of memory, where detrimental effects are reported from the end of the fifth decade (Caselli et al, 2004;Jochemsen et al, 2012;Schultz et al, 2008). The inconsistency of reported findings is likely to stem from several methodological issues, including variation in age group included, control of potential moderators and sensitivity of cognitive tasks used.…”

Section: Introductionmentioning

confidence: 99%

The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Lancaster

Tabet

Rusted

2016

Neurobiology of Aging

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Article (Accepted Version) http://sro.sussex.ac.uk Lancaster, Claire, Tabet, Naji and Rusted, Jennifer (2016) The APOE paradox: how do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline. Neurobiology of Aging, This version is available from Sussex Research Online: http://sro.sussex.ac.uk/62415/ This document is made available in accordance with publisher policies and may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the URL above for details on accessing the published version. Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. AbstractPossession of an APOE e4 allele is an established risk factor for Alzheimer's disease, while the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. 66 volunteers, aged 45-55 years, completed three tasks that provided complementary measures of attentional control: prospective memory, sustained attention and inhibition. Performance was compared between e2 carriers, e4 carriers and e3 homozygotes (the population norm). Carriers of the e4 allele showed subtle disadvantages, compared to the e3 group, in accuracy of Stroop task and prospective memory performance. Contrary to expectations, e2 carriers showed performance disadvantages in sustained attention. The finding of detrimental effects in attentional control for both e4 and e2 complicates the current model that proposes opposing effects of these variants on later-life cognition. Future research is needed to understand how cognitive differences develop with increasing age, and the physiological mechanisms that underpin these changes.

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Apolipoprotein E genotype and memory in the sixth decade of life

Cited by 52 publications

References 42 publications

APOE ε4 and cognitive function in early life: A meta-analysis.

APOE ε4 and cognitive function in early life: A meta-analysis.

The Elusive Nature of APOE ε4 in Mid-adulthood: Understanding the Cognitive Profile

The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

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