The effects of apolipoprotein E on non-impaired cognitive functioning: A meta-analysis

Wisdom, Nick M.; Callahan, Jennifer L.; Hawkins, Keith

doi:10.1016/j.neurobiolaging.2009.02.003

Cited by 382 publications

(451 citation statements)

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“…APOE genotype was defined and coded as E4 þ or E4À, depending on the presence of at least one E4 allele, which is consistent with many other studies investigating the effect of APOE E4 status on cognitive functioning. 20,21 The TOMM40 allelic variants were classified into three categories, according to the length of the poly-T repeat, that is, 'short' ( < 20T residues), 'long' (X20T residues) or 'very long' (X30T residues).…”

Section: Discussionmentioning

confidence: 99%

“…Failing to exclude cases of incipient dementia, particularly at follow-up, was an important limitation of some of the above-mentioned longitudinal studies. 8,12 Third, although APOE E4 status might differentially affect various cognitive functions, such as episodic memory and executive functioning, 20,21 some studies only focused on general cognitive ability rather than assessing a range of specific cognitive domains. 12,18 Furthermore, few of the earlier studies have controlled for previous cognitive ability, which may confound the relationship between APOE E4 allele status and age-related cognitive decline, as childhood mental ability accounts for about 50% of the variance associated with cognitive ability in adulthood.…”

Section: Introductionmentioning

confidence: 99%

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APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921

et al. 2011

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Carriers of the APOE E4 allele have an increased risk of developing Alzheimer's disease. However, it is less clear whether APOE E4 status may also be involved in non-pathological cognitive ageing. The present study investigated the associations between APOE genotypes and cognitive change over 8 years in older community-dwelling individuals. APOE genotype was determined in 501 participants of the Lothian Birth Cohort 1921, whose intelligence had been measured in childhood in the Scottish Mental Survey 1932. A polymorphic variant of TOMM40 (rs10524523) was included to differentiate between the effects of the APOE E3 and E4 allelic variants. Cognitive performance on the domains of verbal memory, abstract reasoning and verbal fluency was assessed at mean age 79 years (n = 501), and again at mean ages of 83 (n = 284) and 87 (n = 187). Using linear mixed models adjusted for demographic variables, vascular risk factors and IQ at age 11 years, possession of the APOE E4 allele was associated with a higher relative rate of cognitive decline over the subsequent 8 years for verbal memory and abstract reasoning. Individuals with the long allelic variant of TOMM40, which is linked to APOE E4, showed similar results. Verbal fluency was not affected by APOE E4 status. APOE E2 status was not associated with change in cognitive performance over 8 years. In nondemented older individuals, possession of the APOE E4 allele predicted a higher rate of cognitive decline on tests of verbal memory and abstract reasoning between 79 and 87 years. Thus, possession of the APOE E4 allele may not only predispose to Alzheimer's disease, but also appears to be a risk factor for non-pathological decline in verbal memory and abstract reasoning in the ninth decade of life.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921

et al. 2011

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“…Although we still retained a reasonable sample size compared to other late-life cohort studies, our findings accordingly should be treated with appropriate caution. Third, although our neuropsychological battery assessed a comprehensive range of cognitive domains including executive function and episodic memory, both shown to be sensitive to 4-related effects (3,4), it remains possible that our battery was insufficiently broad to capture the effects of interest. Future work from our laboratories will address this issue using other datasets.…”

Section: Discussionmentioning

confidence: 99%

“…Metaanalyses also suggest both 4-related cognitive deficits, and 2-related cognitive benefits, in later life (3,4). However, there is accumulating evidence that the subclinical phase of dementia precedes eventual diagnosis by several years, even decades.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E ε4 and Later-Life Decline in Cognitive Function and Grip Strength

Batterham¹,

Bunce²,

Christensen³

2013

The American Journal of Geriatric Psychiatry

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Objectives: Presence of the apolipoprotein E (APOE) 4 allele is a risk factor for dementia, while the 2 allele offers protection against dementia. There is also evidence for a relationship between APOE genotype and changes in cognitive function. It is not clear however, whether this relationship stems from undetected disease in persons genetically more vulnerable to dementia. This study examined whether APOE genotype was associated with either initial performance or change in performance on a range of cognitive and noncognitive tasks, after accounting for possible preclinical dementia.Design: A population-based cohort was assessed up to four times over 12 years. Participants:The sample was an Australian cohort of 590 participants aged 70 and over who were genotyped for APOE.Measurements: The outcomes were processing speed, verbal fluency, episodic memory, word recognition, face recognition, grip strength and reaction time.Results: Adjusted latent growth models indicated that 4 carriers had significantly poorer initial memory performance and greater declines in processing speed and word recognition, compared to 2 and 3 carriers. In addition, 2 carriers exhibited significantly less decline in right grip strength than 3 carriers. However, after excluding 125 participants with low global cognition scores, all genotype effects became non-significant.Conclusions: Over a 12 year period, findings indicate that APOE 4-related cognitive decline in older community-dwelling populations is due to a higher likelihood of preclinical dementia among 4 carriers. When possible dementia cases are removed from the analyses, 4 associations with cognitive decline become statistically unreliable. APOE and cognitive decline in late life 3

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“…Berteau-Pavy et al, 2007;Reinvang et al, 2010;Small et al, 2004;Wisdom et al, 2011). Not all studies have been consistent in reporting an effect of APOE e4 in older adulthood, however (e.g.…”

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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The effects of apolipoprotein E on non-impaired cognitive functioning: A meta-analysis

Cited by 382 publications

References 108 publications

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921

Apolipoprotein E ε4 and Later-Life Decline in Cognitive Function and Grip Strength

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

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