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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An individual's genetics affects the impact of many of these risk factors on AD; for example, APOEε4 carriers with low self-reported exercise levels exhibited an increased risk for disease beyond those with either APOEε4 or low exercise alone.
“It has been shown that an individual’s genetics affects the impact of many of these risk factors on AD; for example, APOEε4 carriers with low self-reported exercise levels exhibited an increased risk for disease beyond those with either APOEε4 or low exercise alone [271]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [271]
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“It has been shown that an individual's genetics affects the impact of many of these risk factors on AD; for example, APOE ε4 carriers with low self-reported exercise levels exhibited an increased risk for disease beyond those with either APOE ε4 or low exercise alone (Luck et al., 2014).”
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- Authors
- Luck, T., Riedel-Heller, S. G., Luppa, M., Wiese, B., Köhler, M., Jessen, F., Bickel, H., Weyerer, S., Pentzek, M., König, H.-H., Prokein, J., Ernst, A., Wagner, M., Mösch, E., Werle, J., Fuchs, A., Brettschneider, C., Scherer, M., & Maier, W.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Leipzig University (DE)
- Medizinische Hochschule Hannover (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- University of Bonn (DE)
- TUM Klinikum (DE)
- Heidelberg University (DE)
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Luck, T.
- ORCID
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2013-07-24
- Volume
- 44
- Issue
- 6
- Pages
- 1319-1329
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W1997127462
- Cited by
- 93
- References
- 41
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 4 · 2020: 17 · 2019: 7 · 2018: 6 · 2017: 9 · 2016: 6 · 2015: 1 · 2014: 8 · 2013: 1
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Keywords
- APOE ε4, APOE ε4 genotype, physical activity, gene-environment interaction, dementia risk, Alzheimer's disease, old age, older adults, additive interaction
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Female, Follow-Up Studies, Genotype, Germany, Humans, Life Style, Male, Motor Activity, Apolipoprotein E4, Gene-Environment Interaction
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