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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

Molecular Psychiatry volume 17, pages 315–324 (2012)Cite this article

Abstract

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 non-demented 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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Acknowledgements

We thank the LBC1921 participants. We thank Beverly Roberts and Martha Whiteman for data collection. We thank the Scottish Council for Research in Education for allowing access to the Scottish Mental Survey 1932. The Biotechnology and Biological Sciences Research Council funded data collection for Wave 1; a Royal Society-Wolfson Research Merit Award to IJD funded data collection for Wave 2; a grant from the Scottish Government's Health Directorates Chief Scientist Office supported data collection in Wave 3. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC), Engineering and Physical Sciences Research Council (EPSRC), Economic and Social Research Council (ESRC) and Medical Research Council (MRC) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS)/European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands

    O J G Schiepers

  2. Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK

    O J G Schiepers, S E Harris, A J Gow, J M Starr & I J Deary

  3. Centre for Cognitive Ageing and Cognitive Epidemiology, Medical Genetics Section, University of Edinburgh, Edinburgh, UK

    S E Harris

  4. Department of Psychology, University of Edinburgh, Edinburgh, UK

    A Pattie & C E Brett

  5. Geriatric Medicine unit, University of Edinburgh, Royal Victoria Hospital, Edinburgh, UK

    J M Starr

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Correspondence to I J Deary.

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Schiepers, O., Harris, S., Gow, A. et al. APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921. Mol Psychiatry 17, 315–324 (2012). https://doi.org/10.1038/mp.2010.137

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