title: Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer's disease.
abstract: 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.
authors.affiliation: The Manchester Molecular Pathology Innovation Centre, University of Manchester, 3rd Floor Citylabs, Nelson St, Manchester, M13 9NQ, UK. nophar.geifman@manchester.ac.uk.|Health eResearch Centre, Division of Informatics, Imaging & Data Sciences, University of Manchester, Manchester, UK. nophar.geifman@manchester.ac.uk.
authors.forename: Nophar
authors.identifier: http://orcid.org/0000-0003-2956-6676
authors.initials: N
authors.lastname: Geifman
authors.affiliation: Center for Innovation in Brain Science, School of Medicine, Departments of Pharmacology and Neurology, University of Arizona, Tucson, AZ, USA.
authors.forename: Roberta Diaz
authors.initials: RD
authors.lastname: Brinton
authors.affiliation: School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Kennedy
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Lon S
authors.initials: LS
authors.lastname: Schneider
authors.affiliation: Institute for Computational Health Sciences, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000453:epidemiology; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000627:therapeutic use*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018697:Nootropic Agents
keywords: Alzheimer’s disease; Apolipoprotein E; Clinical trials; Cognitive function; Meta-analysis; Statins