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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

Published online by Cambridge University Press:  24 July 2013

T. Luck ,
S. G. Riedel-Heller ,
M. Luppa ,
B. Wiese ,
M. Köhler ,
F. Jessen ,
H. Bickel ,
S. Weyerer ,
M. Pentzek  and
H.-H. König
...Show all authors
T. Luck*
Affiliation:
Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Germany Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada
S. G. Riedel-Heller
Affiliation:
Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Germany
M. Luppa
Affiliation:
Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Germany
B. Wiese
Affiliation:
Institute for Biometrics, Hannover Medical School, Germany
M. Köhler
Affiliation:
Centre for Psychosocial Medicine, Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Germany
F. Jessen
Affiliation:
Department of Psychiatry, University of Bonn, Germany DZNE, German Centre for Neurodegenerative Diseases, Bonn, Germany
H. Bickel
Affiliation:
Department of Psychiatry, Klinikum rechts der Isar, Technical University of Munich, Germany
S. Weyerer
Affiliation:
Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
M. Pentzek
Affiliation:
Medical Faculty, Institute of General Practice, Heinrich-Heine-University Düsseldorf, Germany
H.-H. König
Affiliation:
Department of Medical Sociology and Health Economics, University Medical Centre Hamburg-Eppendorf, Germany
J. Prokein
Affiliation:
Institute for Biometrics, Hannover Medical School, Germany
A. Ernst
Affiliation:
Centre for Psychosocial Medicine, Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Germany
M. Wagner
Affiliation:
Department of Psychiatry, University of Bonn, Germany DZNE, German Centre for Neurodegenerative Diseases, Bonn, Germany
E. Mösch
Affiliation:
Department of Psychiatry, Klinikum rechts der Isar, Technical University of Munich, Germany
J. Werle
Affiliation:
Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
A. Fuchs
Affiliation:
Medical Faculty, Institute of General Practice, Heinrich-Heine-University Düsseldorf, Germany
C. Brettschneider
Affiliation:
Department of Medical Sociology and Health Economics, University Medical Centre Hamburg-Eppendorf, Germany
M. Scherer
Affiliation:
Centre for Psychosocial Medicine, Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Germany
W. Maier
Affiliation:
Department of Psychiatry, University of Bonn, Germany DZNE, German Centre for Neurodegenerative Diseases, Bonn, Germany
*
*Address for correspondence: Dr T. Luck, University of Leipzig, Institute of Social Medicine, Occupational Health and Public Health, Philipp-Rosenthal-Str. 55, 04103 Leipzig, Germany. (Email: tobias.luck@medizin.uni-leipzig.de)
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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.

Keywords

Additive interactionapolipoprotein E epsilon 4dementiagene–environment interactionlifestylephysical activity
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 6 , April 2014 , pp. 1319 - 1329
Copyright
Copyright © Cambridge University Press 2013 

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