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.

doi:10.1186/s13195-017-0237-y

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

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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Lowering cholesterol in APOE4 carriers may decrease the risk of dementia.
“As lowering cholesterol in APOE4 carriers may decrease the risk of dementia based on other published literature [27, 28, 29, 30, 31, 32]”
From Blood PCSK9 Impacts Alzheimer's Disease Risk in an <i>APOE</i> Genotype‐Dependent Manner: A Prospective Cohort Study (2026) · cites this paper as [30]
The Background proposes that any preventive effect of statins might be more evident in ApoE4 carriers. The Results report lower Alzheimer’s disease risk among statin users overall and slower cognitive decline among ApoE4-homozygous patients who already had Alzheimer’s disease. They do not establish that lowering cholesterol reduces dementia risk specifically in ApoE4 carriers. (LLM, conf=0.86)
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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: Geifman, Nophar
Kennedy, Richard E.
Schneider, Lon S.
Butte, Atul J.
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: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
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: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Surgery › 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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Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease

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