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Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene-environment interaction for the risk of dementia and Alzheimer's disease dementia.

Abstract

BACKGROUND

As physical activity may modify the effect of the apolipoprotein E (APOE) ε4 allele on the risk of dementia and Alzheimer's disease (AD) dementia, we tested for such a gene-environment interaction in a sample of general practice patients aged ⩾75 years.

METHOD

Data were derived from follow-up waves I-IV of the longitudinal German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). The Kaplan-Meier survival method was used to estimate dementia- and AD-free survival times. Multivariable Cox regression was used to assess individual associations of APOE ε4 and physical activity with risk for dementia and AD, controlling for covariates. We tested for gene-environment interaction by calculating three indices of additive interaction.

RESULTS

Among the randomly selected sample of 6619 patients, 3327 (50.3%) individuals participated in the study at baseline and 2810 (42.5%) at follow-up I. Of the 2492 patients without dementia included at follow-up I, 278 developed dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The presence of the APOE ε4 allele significantly increased and higher physical activity significantly decreased risk for dementia and AD. The co-presence of APOE ε4 with low physical activity was associated with higher risk for dementia and AD and shorter dementia- and AD-free survival time than the presence of APOE ε4 or low physical activity alone. Indices of interaction indicated no significant interaction between low physical activity and the APOE ε4 allele for general dementia risk, but a possible additive interaction for AD risk.

CONCLUSIONS

Physical activity even in late life may be effective in reducing conversion to dementia and AD or in delaying the onset of clinical manifestations. APOE ε4 carriers may particularly benefit from increasing physical activity with regard to their risk for AD.

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  • Authors+Show Affiliations

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    Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Germany.

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    Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Germany.

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    Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Germany.

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    Institute for Biometrics, Hannover Medical School, Germany.

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    Centre for Psychosocial Medicine, Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Germany.

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    Department of Psychiatry, University of Bonn, Germany.

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    Department of Psychiatry, Klinikum rechts der Isar, Technical University of Munich, Germany.

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    Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.

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    Medical Faculty, Institute of General Practice, Heinrich-Heine-University Düsseldorf, Germany.

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    Department of Medical Sociology and Health Economics, University Medical Centre Hamburg-Eppendorf, Germany.

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    Institute for Biometrics, Hannover Medical School, Germany.

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    Centre for Psychosocial Medicine, Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Germany.

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    Department of Psychiatry, University of Bonn, Germany.

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    Department of Psychiatry, Klinikum rechts der Isar, Technical University of Munich, Germany.

    ,

    Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.

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    Medical Faculty, Institute of General Practice, Heinrich-Heine-University Düsseldorf, Germany.

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    Department of Medical Sociology and Health Economics, University Medical Centre Hamburg-Eppendorf, Germany.

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    Centre for Psychosocial Medicine, Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Germany.

    Department of Psychiatry, University of Bonn, Germany.

    Source

    Psychological medicine 44:6 2014 Apr pg 1319-29

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Apolipoprotein E4
    Dementia
    Female
    Follow-Up Studies
    Gene-Environment Interaction
    Genotype
    Germany
    Humans
    Life Style
    Male
    Motor Activity

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    23883793

    Citation

    Luck, T, et al. "Apolipoprotein E Epsilon 4 Genotype and a Physically Active Lifestyle in Late Life: Analysis of Gene-environment Interaction for the Risk of Dementia and Alzheimer's Disease Dementia." Psychological Medicine, vol. 44, no. 6, 2014, pp. 1319-29.
    Luck T, Riedel-Heller SG, Luppa M, et al. Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene-environment interaction for the risk of dementia and Alzheimer's disease dementia. Psychol Med. 2014;44(6):1319-29.
    Luck, T., Riedel-Heller, S. G., Luppa, M., Wiese, B., Köhler, M., Jessen, F., ... Maier, W. (2014). Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene-environment interaction for the risk of dementia and Alzheimer's disease dementia. Psychological Medicine, 44(6), pp. 1319-29. doi:10.1017/S0033291713001918.
    Luck T, et al. Apolipoprotein E Epsilon 4 Genotype and a Physically Active Lifestyle in Late Life: Analysis of Gene-environment Interaction for the Risk of Dementia and Alzheimer's Disease Dementia. Psychol Med. 2014;44(6):1319-29. PubMed PMID: 23883793.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene-environment interaction for the risk of dementia and Alzheimer's disease dementia. AU - Luck,T, AU - Riedel-Heller,S G, AU - Luppa,M, AU - Wiese,B, AU - Köhler,M, AU - Jessen,F, AU - Bickel,H, AU - Weyerer,S, AU - Pentzek,M, AU - König,H-H, AU - Prokein,J, AU - Ernst,A, AU - Wagner,M, AU - Mösch,E, AU - Werle,J, AU - Fuchs,A, AU - Brettschneider,C, AU - Scherer,M, AU - Maier,W, Y1 - 2013/07/24/ PY - 2013/7/26/entrez PY - 2013/7/26/pubmed PY - 2015/4/1/medline SP - 1319 EP - 29 JF - Psychological medicine JO - Psychol Med VL - 44 IS - 6 N2 - BACKGROUND: As physical activity may modify the effect of the apolipoprotein E (APOE) ε4 allele on the risk of dementia and Alzheimer's disease (AD) dementia, we tested for such a gene-environment interaction in a sample of general practice patients aged ⩾75 years. METHOD: Data were derived from follow-up waves I-IV of the longitudinal German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). The Kaplan-Meier survival method was used to estimate dementia- and AD-free survival times. Multivariable Cox regression was used to assess individual associations of APOE ε4 and physical activity with risk for dementia and AD, controlling for covariates. We tested for gene-environment interaction by calculating three indices of additive interaction. RESULTS: Among the randomly selected sample of 6619 patients, 3327 (50.3%) individuals participated in the study at baseline and 2810 (42.5%) at follow-up I. Of the 2492 patients without dementia included at follow-up I, 278 developed dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The presence of the APOE ε4 allele significantly increased and higher physical activity significantly decreased risk for dementia and AD. The co-presence of APOE ε4 with low physical activity was associated with higher risk for dementia and AD and shorter dementia- and AD-free survival time than the presence of APOE ε4 or low physical activity alone. Indices of interaction indicated no significant interaction between low physical activity and the APOE ε4 allele for general dementia risk, but a possible additive interaction for AD risk. CONCLUSIONS: Physical activity even in late life may be effective in reducing conversion to dementia and AD or in delaying the onset of clinical manifestations. APOE ε4 carriers may particularly benefit from increasing physical activity with regard to their risk for AD. SN - 1469-8978 UR - https://www.unboundmedicine.com/medline/citation/23883793/Apolipoprotein_E_epsilon_4_genotype_and_a_physically_active_lifestyle_in_late_life:_analysis_of_gene_environment_interaction_for_the_risk_of_dementia_and_Alzheimer's_disease_dementia_ L2 - https://www.cambridge.org/core/product/identifier/S0033291713001918/type/journal_article DB - PRIME DP - Unbound Medicine ER -