Sex and APOE genotype differences related to statin use in the aging population
Abstract Background Significant evidence suggests that the cholesterol‐lowering statins can affect cognitive function and reduce the risk for Alzheimer's disease (AD) and dementia. These potential effects may be constrained by specific combinations of an individual's sex and apolipoprotein...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/trc2.12156 |
| _version_ | 1797984920502534144 |
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| author | Arianna Dagliati Niels Peek Roberta Diaz Brinton Nophar Geifman |
| author_facet | Arianna Dagliati Niels Peek Roberta Diaz Brinton Nophar Geifman |
| author_sort | Arianna Dagliati |
| collection | DOAJ |
| description | Abstract Background Significant evidence suggests that the cholesterol‐lowering statins can affect cognitive function and reduce the risk for Alzheimer's disease (AD) and dementia. These potential effects may be constrained by specific combinations of an individual's sex and apolipoprotein E (APOE) genotype. Methods Here we examine data from 252,327 UK Biobank participants, aged 55 or over, and compare the effects of statin use in males and females. We assessed difference in statin treatments taking a matched cohort approach, and identified key stratifiers using regression models and conditional inference trees. Using statistical modeling, we further evaluated the effect of statins on survival, cognitive decline over time, and on AD prevalence. Results We identified that in the selected population, males were older, had a higher level of education, better cognitive scores, higher incidence of cardiovascular and metabolic diseases, and a higher rate of statin use. We observed that males and those participants with an APOE ε4–positive genotype had higher probabilities of being treated with statins; while participants with an AD diagnosis had slightly lower probabilities. We found that use of statins was not significantly associated with overall higher rates of survival. However, when considering the interaction of statin use with sex, the results suggest higher survival rates in males treated with statins. Finally, examination of cognitive function indicates a potential beneficial effect of statins that is selective for APOE ε4–positive genotypes. Discussion Our evaluation of the aging population in a large cohort from the UK Biobank confirms sex and APOE genotype as fundamental risk stratifiers for AD and cognitive function, furthermore it extends them to the specific area of statin use, clarifying their specific interactions with treatments. |
| first_indexed | 2024-04-11T07:10:32Z |
| format | Article |
| id | doaj.art-cde170fea57345df93008f6c3be75afe |
| institution | Directory Open Access Journal |
| issn | 2352-8737 |
| language | English |
| last_indexed | 2024-04-11T07:10:32Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj.art-cde170fea57345df93008f6c3be75afe2022-12-22T04:38:14ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372021-01-0171n/an/a10.1002/trc2.12156Sex and APOE genotype differences related to statin use in the aging populationArianna Dagliati0Niels Peek1Roberta Diaz Brinton2Nophar Geifman3Centre for Health Informatics University of Manchester Manchester UKCentre for Health Informatics University of Manchester Manchester UKDepartment of Pharmacology College of Medicine University of Arizona Tucson Arizona USACentre for Health Informatics University of Manchester Manchester UKAbstract Background Significant evidence suggests that the cholesterol‐lowering statins can affect cognitive function and reduce the risk for Alzheimer's disease (AD) and dementia. These potential effects may be constrained by specific combinations of an individual's sex and apolipoprotein E (APOE) genotype. Methods Here we examine data from 252,327 UK Biobank participants, aged 55 or over, and compare the effects of statin use in males and females. We assessed difference in statin treatments taking a matched cohort approach, and identified key stratifiers using regression models and conditional inference trees. Using statistical modeling, we further evaluated the effect of statins on survival, cognitive decline over time, and on AD prevalence. Results We identified that in the selected population, males were older, had a higher level of education, better cognitive scores, higher incidence of cardiovascular and metabolic diseases, and a higher rate of statin use. We observed that males and those participants with an APOE ε4–positive genotype had higher probabilities of being treated with statins; while participants with an AD diagnosis had slightly lower probabilities. We found that use of statins was not significantly associated with overall higher rates of survival. However, when considering the interaction of statin use with sex, the results suggest higher survival rates in males treated with statins. Finally, examination of cognitive function indicates a potential beneficial effect of statins that is selective for APOE ε4–positive genotypes. Discussion Our evaluation of the aging population in a large cohort from the UK Biobank confirms sex and APOE genotype as fundamental risk stratifiers for AD and cognitive function, furthermore it extends them to the specific area of statin use, clarifying their specific interactions with treatments.https://doi.org/10.1002/trc2.12156aging populationAlzheimer's diseaseAPOE genotypestatinsUK Biobank |
| spellingShingle | Arianna Dagliati Niels Peek Roberta Diaz Brinton Nophar Geifman Sex and APOE genotype differences related to statin use in the aging population Alzheimer’s & Dementia: Translational Research & Clinical Interventions aging population Alzheimer's disease APOE genotype statins UK Biobank |
| title | Sex and APOE genotype differences related to statin use in the aging population |
| title_full | Sex and APOE genotype differences related to statin use in the aging population |
| title_fullStr | Sex and APOE genotype differences related to statin use in the aging population |
| title_full_unstemmed | Sex and APOE genotype differences related to statin use in the aging population |
| title_short | Sex and APOE genotype differences related to statin use in the aging population |
| title_sort | sex and apoe genotype differences related to statin use in the aging population |
| topic | aging population Alzheimer's disease APOE genotype statins UK Biobank |
| url | https://doi.org/10.1002/trc2.12156 |
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