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Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies

BACKGROUND: Numerous risk factors for dementia are well established, though the causal nature of these associations remains unclear. OBJECTIVE: To systematically review Mendelian randomization (MR) studies investigating causal relationships between risk factors and global cognitive function or demen...

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Autores principales: Kuźma, Elżbieta, Hannon, Eilis, Zhou, Ang, Lourida, Ilianna, Bethel, Alison, Levine, Deborah A., Lunnon, Katie, Thompson-Coon, Jo, Hyppönen, Elina, Llewellyn, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004893/
https://www.ncbi.nlm.nih.gov/pubmed/29865062
http://dx.doi.org/10.3233/JAD-180013
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author Kuźma, Elżbieta
Hannon, Eilis
Zhou, Ang
Lourida, Ilianna
Bethel, Alison
Levine, Deborah A.
Lunnon, Katie
Thompson-Coon, Jo
Hyppönen, Elina
Llewellyn, David J.
author_facet Kuźma, Elżbieta
Hannon, Eilis
Zhou, Ang
Lourida, Ilianna
Bethel, Alison
Levine, Deborah A.
Lunnon, Katie
Thompson-Coon, Jo
Hyppönen, Elina
Llewellyn, David J.
author_sort Kuźma, Elżbieta
collection PubMed
description BACKGROUND: Numerous risk factors for dementia are well established, though the causal nature of these associations remains unclear. OBJECTIVE: To systematically review Mendelian randomization (MR) studies investigating causal relationships between risk factors and global cognitive function or dementia. METHODS: We searched five databases from inception to February 2017 and conducted citation searches including MR studies investigating the association between any risk factor and global cognitive function, all-cause dementia or dementia subtypes. Two reviewers independently assessed titles and abstracts, full-texts, and study quality. RESULTS: We included 18 MR studies investigating education, lifestyle factors, cardiovascular factors and related biomarkers, diabetes related and other endocrine factors, and telomere length. Studies were of predominantly good quality, however eight received low ratings for sample size and statistical power. The most convincing causal evidence was found for an association of shorter telomeres with increased risk of Alzheimer’s disease (AD). Causal evidence was weaker for smoking quantity, vitamin D, homocysteine, systolic blood pressure, fasting glucose, insulin sensitivity, and high-density lipoprotein cholesterol. Well-replicated associations were not present for most exposures and we cannot fully discount survival and diagnostic bias, or the potential for pleiotropic effects. CONCLUSIONS: Genetic evidence supported a causal association between telomere length and AD, whereas limited evidence for other risk factors was largely inconclusive with tentative evidence for smoking quantity, vitamin D, homocysteine, and selected metabolic markers. The lack of stronger evidence for other risk factors may reflect insufficient statistical power. Larger well-designed MR studies would therefore help establish the causal status of these dementia risk factors.
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spelling pubmed-60048932018-06-25 Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies Kuźma, Elżbieta Hannon, Eilis Zhou, Ang Lourida, Ilianna Bethel, Alison Levine, Deborah A. Lunnon, Katie Thompson-Coon, Jo Hyppönen, Elina Llewellyn, David J. J Alzheimers Dis Research Article BACKGROUND: Numerous risk factors for dementia are well established, though the causal nature of these associations remains unclear. OBJECTIVE: To systematically review Mendelian randomization (MR) studies investigating causal relationships between risk factors and global cognitive function or dementia. METHODS: We searched five databases from inception to February 2017 and conducted citation searches including MR studies investigating the association between any risk factor and global cognitive function, all-cause dementia or dementia subtypes. Two reviewers independently assessed titles and abstracts, full-texts, and study quality. RESULTS: We included 18 MR studies investigating education, lifestyle factors, cardiovascular factors and related biomarkers, diabetes related and other endocrine factors, and telomere length. Studies were of predominantly good quality, however eight received low ratings for sample size and statistical power. The most convincing causal evidence was found for an association of shorter telomeres with increased risk of Alzheimer’s disease (AD). Causal evidence was weaker for smoking quantity, vitamin D, homocysteine, systolic blood pressure, fasting glucose, insulin sensitivity, and high-density lipoprotein cholesterol. Well-replicated associations were not present for most exposures and we cannot fully discount survival and diagnostic bias, or the potential for pleiotropic effects. CONCLUSIONS: Genetic evidence supported a causal association between telomere length and AD, whereas limited evidence for other risk factors was largely inconclusive with tentative evidence for smoking quantity, vitamin D, homocysteine, and selected metabolic markers. The lack of stronger evidence for other risk factors may reflect insufficient statistical power. Larger well-designed MR studies would therefore help establish the causal status of these dementia risk factors. IOS Press 2018-06-08 /pmc/articles/PMC6004893/ /pubmed/29865062 http://dx.doi.org/10.3233/JAD-180013 Text en © 2018 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kuźma, Elżbieta
Hannon, Eilis
Zhou, Ang
Lourida, Ilianna
Bethel, Alison
Levine, Deborah A.
Lunnon, Katie
Thompson-Coon, Jo
Hyppönen, Elina
Llewellyn, David J.
Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies
title Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies
title_full Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies
title_fullStr Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies
title_full_unstemmed Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies
title_short Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies
title_sort which risk factors causally influence dementia? a systematic review of mendelian randomization studies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004893/
https://www.ncbi.nlm.nih.gov/pubmed/29865062
http://dx.doi.org/10.3233/JAD-180013
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