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Cited by 191Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchLipoproteins and Cardiovascular Health

The DOI matches its Crossref record; 76 of the 77 references it cites were found in a registry or an index.

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

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Geifman, Nophar, Brinton, Roberta Diaz, Kennedy, Richard E., Schneider, Lon S., Butte, Atul J.·2017·Alzheimer's Research & Therapy
DOI 10.1186/s13195-017-0237-yPMC PMC5316146
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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.

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Crossref · 10.1186/s13195-017-0237-y

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Fig. 1 Analyses workflows. a Re-analysis of simvastatin trial. b Analysis of continual use of statins from multiple AD trials and studies. c Analysis of statin use from the ROS/MAP studies. AD Alzheimer’s disease, MAP Memory Aging Project, ROS Religious Order Study
Fig. 1 Analyses workflows. a Re-analysis of simvastatin trial. b Analysis of continual use of statins from multiple AD trials and studies. c Analysis of statin use from the ROS/MAP studies. AD Alzheimer’s disease, MAP Memory Aging Project, ROS Religious Order StudyCC BY · PubMed Central
Fig. 2 ADAS-cog scores in subjects treated with simvastatin or placebo. a ADAS-cog scores over time in different genotype subgroups. b Change in ADAS-cog scores from baseline in different genotype subgroups. ADAS-cog Alzheimer’s Disease Assessment Scale—cognitive subscale, ApoE apolipoprotein E
Fig. 2 ADAS-cog scores in subjects treated with simvastatin or placebo. a ADAS-cog scores over time in different genotype subgroups. b Change in ADAS-cog scores from baseline in different genotype subgroups. ADAS-cog Alzheimer’s Disease Assessment Scale—cognitive subscale, ApoE apolipoprotein ECC BY · PubMed Central
Fig. 3 Continual use of statins vs placebo. a ADAS-cog scores at baseline. b Continual use of different statins vs no statin use. *Significant differences between statin users and nonusers (p < 0.05). ADAS-cog Alzheimer’s Disease Assessment Scale—cognitive subscale
Fig. 3 Continual use of statins vs placebo. a ADAS-cog scores at baseline. b Continual use of different statins vs no statin use. *Significant differences between statin users and nonusers (p < 0.05). ADAS-cog Alzheimer’s Disease Assessment Scale—cognitive subscaleCC BY · PubMed Central
Fig. 4 Effect of continual use of statins on global cognitive scores and MMSE scores. Top panels: illustration of differences in the change in scores (from baseline) in statin users and nonusers. Bottom panels: illustration of differences in scores between statin users and nonusers. Left-hand panels: global cognitive score. Right-hand panels: MMSE score. Plot lines were smoothed using the locally weighted scatterplot smoothing (LOESS) method; shaded areas represent the 0.95 confidence interval (blue line, statin users; red line, statin nonusers). MMSE Mini-Mental State Examination
Fig. 4 Effect of continual use of statins on global cognitive scores and MMSE scores. Top panels: illustration of differences in the change in scores (from baseline) in statin users and nonusers. Bottom panels: illustration of differences in scores between statin users and nonusers. Left-hand panels: global cognitive score. Right-hand panels: MMSE score. Plot lines were smoothed using the locally weighted scatterplot smoothing (LOESS) method; shaded areas represent the 0.95 confidence interval (blue line, statin users; red line, statin nonusers). MMSE Mini-Mental State ExaminationCC BY · PubMed Central

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Research works printed but not linked: 1

  1. National Institute on Aging. Alzheimer's Disease Progress Report 2014–2015: Advancing Research Toward a Cure. Bethesda: National Institute on Aging; 2015.

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Metadata

Authors
Geifman, N., Brinton, R. D., Kennedy, R. E., Schneider, L. S., & Butte, A. J.
Affiliations
  • University of Manchester (GB)
  • University of Alabama at Birmingham (US)
  • University of Southern California (US)
  • University of California, San Francisco (US)
Corresponding author
Geifman, Nophar
ORCID
Venue
Alzheimer's Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2017-02-17
Volume
9
Issue
1
Pages
10-10
ISSN
1758-9193 (ISSN-L)
DOI
10.1186/s13195-017-0237-y
PMC
PMC5316146
OpenAlex
W2588146368
Cited by
191
References
77
Citations by year
2026: 9 · 2025: 13 · 2024: 20 · 2023: 19 · 2022: 30 · 2021: 22 · 2020: 24 · 2019: 18 · 2018: 28 · 2017: 8
FWCI
2.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s Research & Therapy (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UA Campus Repository (The University of Arizona) (acceptedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Research Explorer (The University of Manchester) (submittedVersion, other-oa)
Funders
  • National Institute on Aging (R34 AG049652)
  • James H. Zumberge Faculty Research and Innovation Fund at the University of Southern California (NA)
  • National Institutes of Health (R01 AG037561)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Keywords
statins, Alzheimer's disease, cognitive decline, simvastatin, APOE ε4, cholesterol, amyloid-beta, dementia risk, endotypes, statin therapy response, long-term statin use
MeSH terms
Alzheimer Disease, Humans, Nootropic Agents, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cognitive Dysfunction

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