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Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease

BACKGROUND: Despite substantial research and development investment in Alzheimer’s disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated wit...

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Autores principales: Geifman, Nophar, Brinton, Roberta Diaz, Kennedy, Richard E., Schneider, Lon S., Butte, Atul J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316146/
https://www.ncbi.nlm.nih.gov/pubmed/28212683
http://dx.doi.org/10.1186/s13195-017-0237-y
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author Geifman, Nophar
Brinton, Roberta Diaz
Kennedy, Richard E.
Schneider, Lon S.
Butte, Atul J.
author_facet Geifman, Nophar
Brinton, Roberta Diaz
Kennedy, Richard E.
Schneider, Lon S.
Butte, Atul J.
author_sort Geifman, Nophar
collection PubMed
description BACKGROUND: Despite substantial research and development investment in Alzheimer’s disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy. METHODS: Here we investigate the possible protective and therapeutic effect of statins in AD through the analysis of datasets of integrated clinical trials, and prospective observational studies. RESULTS: Re-analysis of AD patient-level data from failed clinical trials suggested by trend that use of simvastatin may slow the progression of cognitive decline, and to a greater extent in ApoE4 homozygotes. Evaluation of continual long-term use of various statins, in participants from multiple studies at baseline, revealed better cognitive performance in statin users. These findings were supported in an additional, observational cohort where the incidence of AD was significantly lower in statin users, and ApoE4/ApoE4-genotyped AD patients treated with statins showed better cognitive function over the course of 10-year follow-up. CONCLUSIONS: These results indicate that the use of statins may benefit all AD patients with potentially greater therapeutic efficacy in those homozygous for ApoE4.
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spelling pubmed-53161462017-02-24 Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease Geifman, Nophar Brinton, Roberta Diaz Kennedy, Richard E. Schneider, Lon S. Butte, Atul J. Alzheimers Res Ther Research BACKGROUND: Despite substantial research and development investment in Alzheimer’s disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy. METHODS: Here we investigate the possible protective and therapeutic effect of statins in AD through the analysis of datasets of integrated clinical trials, and prospective observational studies. RESULTS: Re-analysis of AD patient-level data from failed clinical trials suggested by trend that use of simvastatin may slow the progression of cognitive decline, and to a greater extent in ApoE4 homozygotes. Evaluation of continual long-term use of various statins, in participants from multiple studies at baseline, revealed better cognitive performance in statin users. These findings were supported in an additional, observational cohort where the incidence of AD was significantly lower in statin users, and ApoE4/ApoE4-genotyped AD patients treated with statins showed better cognitive function over the course of 10-year follow-up. CONCLUSIONS: These results indicate that the use of statins may benefit all AD patients with potentially greater therapeutic efficacy in those homozygous for ApoE4. BioMed Central 2017-02-17 /pmc/articles/PMC5316146/ /pubmed/28212683 http://dx.doi.org/10.1186/s13195-017-0237-y Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Geifman, Nophar
Brinton, Roberta Diaz
Kennedy, Richard E.
Schneider, Lon S.
Butte, Atul J.
Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease
title Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease
title_full Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease
title_fullStr Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease
title_full_unstemmed Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease
title_short Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease
title_sort evidence for benefit of statins to modify cognitive decline and risk in alzheimer’s disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316146/
https://www.ncbi.nlm.nih.gov/pubmed/28212683
http://dx.doi.org/10.1186/s13195-017-0237-y
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