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dc.contributor.authorGeifman, Nophar
dc.contributor.authorBrinton, Roberta Diaz
dc.contributor.authorKennedy, Richard E.
dc.contributor.authorSchneider, Lon S.
dc.contributor.authorButte, Atul J.
dc.date.accessioned2017-04-24T20:39:31Z
dc.date.available2017-04-24T20:39:31Z
dc.date.issued2017-02-17
dc.identifier.citationEvidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease 2017, 9 (1) Alzheimer's Research & Therapyen
dc.identifier.issn1758-9193
dc.identifier.pmid28212683
dc.identifier.doi10.1186/s13195-017-0237-y
dc.identifier.urihttp://hdl.handle.net/10150/623238
dc.description.abstractBackground: Despite substantial research and development investment in Alzheimer's disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, beta-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.
dc.description.sponsorshipNational Institute on Aging "Systems Pharmacology for Predictive Alzheimer's Therapeutics: SysPharmRx-AD" [R34 AG049652]; University of Southern California; James H. Zumberge Faculty Research and Innovation Fund at the University of Southern California; NIA [P30AG10161, R01AG15819I9, R01AG17917]en
dc.language.isoenen
dc.publisherBIOMED CENTRAL LTDen
dc.relation.urlhttp://alzres.biomedcentral.com/articles/10.1186/s13195-017-0237-yen
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License.en
dc.subjectStatinsen
dc.subjectAlzheimer's diseaseen
dc.subjectApolipoprotein Een
dc.subjectCognitive functionen
dc.subjectMeta-analysisen
dc.subjectClinical trialsen
dc.titleEvidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s diseaseen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Sch Med, Ctr Innovat Brain Sci, Dept Pharmacol & Neurolen
dc.identifier.journalAlzheimer's Research & Therapyen
dc.description.noteOpen Access Journal.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2018-09-11T18:53:23Z
html.description.abstractBackground: Despite substantial research and development investment in Alzheimer's disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, beta-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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