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Association of Alzheimer’s related genotypes with cognitive decline in multiple domains: results from the Three-City Dijon study

Molecular Psychiatry volume 20, pages 1173–1178 (2015)Cite this article

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Abstract

Several genetic polymorphisms have been associated with Late Onset Alzheimer’s Disease (LOAD), but there has been limited evidence on whether these polymorphisms predict intermediary stage outcomes such as cognitive changes in prospective community-based studies. Our aim was to evaluate whether polymorphisms previously established as predictors of LOAD also predict worse cognitive function and accelerated decline across multiple cognitive domains. We analyzed data from the 3C-Dijon study, in which 4931 respondents aged 65+ were examined up to 5 times over 10 years with a neuropsychological assessment. We evaluated the associations of polymorphisms in APOE, CR1, BIN1, CLU, PICALM, ABCA7, MS4A6A, CD33, MS4A4E and CD2AP with level and change in 5 neuropsychological tests, assuming a dominant effect model. To optimize measurement, we used a mixed regression model with a latent process for each cognitive domain: global cognition (Mini Mental State Examination); verbal fluency (Isaac’s Set Test); visual memory (Benton Visual Retention Test); information processing (Trail Making Test B) and literacy (National Adult Reading Test). APOE was associated with accelerated decline in global cognition and verbal fluency. Only two non-APOE genetic polymorphisms were associated with cognitive decline: CR1 was associated with rate of change in verbal fluency and BIN1 was associated with rate of change in global cognition. In a large prospective population-based study of dementia-free individuals, only a few cognitive domains were associated with established LOAD risk alleles. The most consistent associations were for global cognition and verbal fluency.

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Acknowledgements

Institut National de la Santé et de la Recherche Médicale (INSERM), the Victor Segalen-Bordeaux II University, Fondation Plan Alzheimer, the Sanofi-Synthélabo Company, Fondation pour la Recherche Médicale, Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Haute Autorité de la Santé, Institut National de Prévention et d'Education pour la Santé (INPES), Conseils Régionaux of Bourgogne, Fondation de France, the Ministry of Research-INSERM Program 'Cohortes et collections de données biologiques', Mutuelle Générale de l'Education Nationale, Institut de la Longévité and Conseil Général de la Côte d'or. Maria Glymour received support from the National Institute on Aging (AG034385). We thank the study participants and the 3C-Dijon team (coordinators, psychometrists, psychologists, program management team, and physicians) for their help in conducting this study.

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Authors and Affiliations

  1. Bordeaux University, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique & CIC-1401, CHU de Bordeaux, Pole de Sante Publique, Bordeaux, France

    A Vivot, C Tzourio, G Chêne & C Dufouil

  2. Department of Social and Behavorial Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    A Vivot & M M Glymour

  3. Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA, USA

    M M Glymour

  4. Lille University, INSERM U744, Institut Pasteur de Lille, Lille, France

    P Amouyel

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  1. A Vivot
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Correspondence to C Dufouil.

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The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

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Vivot, A., Glymour, M., Tzourio, C. et al. Association of Alzheimer’s related genotypes with cognitive decline in multiple domains: results from the Three-City Dijon study. Mol Psychiatry 20, 1173–1178 (2015). https://doi.org/10.1038/mp.2015.62

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