The Combined Effects of Apolipoprotein E Polymorphism and Low-Density Lipoprotein Cholesterol on Cognitive Performance in Young Adults

Puttonen, Sampsa; Elovainio, Marko; Kivimäki, Mika; Lehtimäki, Terho; Keltikangas‐Järvinen, Liisa

doi:10.1159/000071827

Cited by 34 publications

(24 citation statements)

References 37 publications

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“…One reason for this may be variation in the statistical power for individual studies. Whereas some studies with large sample sizes, and therefore high statistical power, found no differences (e.g., Deary et al, 2003;Jorm et al, 2007;Taylor et al, in press), other studies with small sample sizes, and therefore lower statistical power, did find APOE ɛ4-related benefits (e.g., Acevedo et al, 2010;Marchant et al, 2010;Puttonen et al, 2003;Yu et al, 2000). Type I or II errors may explain some of the variation in findings, but generally studies with small Ns tend to either over-or underestimate effect sizes, whereas investigations with large Ns estimate effect sizes more accurately.…”

Section: It Is Clear That There Are Inconsistencies In Research Findimentioning

confidence: 99%

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: It Is Clear That There Are Inconsistencies In Research Findimentioning

confidence: 99%

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

Ihle¹,

Bunce²,

Kliegel³

2012

Neuropsychology

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“…APOE-ε4 has been associated with higher rates of cognitive decline during normal aging [1,2] and with aggravating incidence in the context of several neurological disorders, including Alzheimer's disease. Intriguingly, several studies reported higher performances on global cognition, attention and episodic memory in young adult APOE-ε4 carriers compared to non-APOE-ε4 carriers [3][4][5][6]. Better cognitive functions with APOE-ε4 during the first decades of life followed by a negative influence after the fifth decade was interpreted as an antagonistic pleiotropic effect [6].…”

Section: Introductionmentioning

confidence: 99%

ApoE4 confers better spatial memory than apoE3 in young adult hAPP-Yac/apoE-TR mice

Moreau

Bott

Zerbinatti

et al. 2013

Behavioural Brain Research

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“…hypertension, high cholesterol and diabetes (Atzmon et al, 2002;Köhler et al, 2014;van Exel et al, 2002;Whitmer, Sidney, Selby, Johnston, & Yaffe, 2005), and interactions between vascular health, APOE and cognition are reported (de Frias, Schaie, & Willis, 2014;Peila et al, 2001;Puttonen, Elovainio, Kivimäki, Lehtimäki, & Keltikangas-Järvinen, 2003;Zade et al, 2010). Current behavioural research is neither considering the potential modifying effects of wider risk factors nor adequately controlling for them, though they undoubtedly contribute to the cognitive ageing trajectory (Herrup, 2010).…”

Section: Discussionmentioning

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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The Combined Effects of Apolipoprotein E Polymorphism and Low-Density Lipoprotein Cholesterol on Cognitive Performance in Young Adults

Cited by 34 publications

References 37 publications

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

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

ApoE4 confers better spatial memory than apoE3 in young adult hAPP-Yac/apoE-TR mice

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

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