Home › Research › Treatments
HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer's disease and why it would be ill-advise to use one that crosses the blood-brain barrier
Sparks DL, Connor DJ, Browne PJ, Lopez JE, Sabbagh MN.. The journal of nutrition, health & aging, 2002-01-01
Topic: Amyloid, tau and blood-test diagnosis
Increased circulating cholesterol has been long linked to an increased risk of coronary artery disease (CAD), and is now linked to an increased risk of developing Alzheimer s disease (AD). We first showed the neuropathologic link between CAD and AD as increased incidence of cerebral senile plaques in both disorders. We then showed that AD-like neuropathology occurred in the brains of cholesterol-fed rabbits; including increased -amyloid (Ab). Currently there are a number of transgenic mouse models of AD that exhibit enhanced Ab pathology if cholesterol diet is administered. Culture studies clearly show that excess cholesterol enhances beta-metabolism of amyloid precursor protein (APP) and production of -amyloidogenic peptides, and that sufficiently reducing cholesterol levels by inhibition of synthesis completely inhibits all beta-metabolism of APP. Our finding that the elevated levels of Ab in rabbits fed cholesterol diet could be cleared from the brain by resuming a control diet prompted the hypothesis that lowering cholesterol levels in the blood of AD patients may be of some clinical benefit. Pilot data suggests that therapeutically lowering circulating cholesterol may attenuate Ab production in the cholesterol-fed rabbit brain, may stabilize cognitive performance in mildly impaired AD patients, and may reduce the risk of developing AD. Accordingly, we have initiated a double-blind treatment trial evaluating Atorvastatin Na+ among 120 mild-to-moderately impaired AD subjects randomized to one of two groups receiving placebo or active drug once a day. Atorvastatin is one of a general class of HMG-CoA reductase inhibitor drugs called statins that lower cholesterol by inhibition of synthesis. We chose to use Atorvastatin in this AD Treatment Trial because it does not cross the blood-brain-barrier, and believe it would be ill-advised to use a statin that does. This position stems from the observations that excess cholesterol inhibits cholesterol synthesis and increases Ab production, that Ab kills cells in part by inhibiting cholesterol synthesis, and that statins acting at the neuronal level could further exacerbate degeneration in AD by further inhibition of necessary cholesterol synthesis.
Key findings
- Increased circulating cholesterol has been long linked to an increased risk of coronary artery disease (CAD), and is now linked to an increased risk of developing Alzheimer s disease (AD).
- We then showed that AD-like neuropathology occurred in the brains of cholesterol-fed rabbits; including increased -amyloid (Ab).
- Pilot data suggests that therapeutically lowering circulating cholesterol may attenuate Ab production in the cholesterol-fed rabbit brain, may stabilize cognitive performance in mildly impaired AD patients, and may reduce the risk of developing AD.
Why it matters
This paper describes animal and culture findings linking cholesterol to amyloid pathology and pilot data suggesting that lowering circulating cholesterol may stabilize cognitive performance in mildly impaired Alzheimer's patients and may reduce risk. It is largely early and preliminary evidence, and it does not establish that statins treat, cure, or prevent Alzheimer's disease.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Evidence strengthHigh
How this study scored 55/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it. We have no data on journal's citation record, so that was left out: it earned 53 of the 96 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of nutrition, health & aging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2002 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 4 / 7 | Cited 82 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.2 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 3 / 6 | Cited 3.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Marwan Noel Sabbagh: h-index 65 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Banner Sun Health Research Institute: institution h-index 285 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12474023) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 53 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 53 of the 96 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. This record has no DOI, so the citation leaves it out. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Sparks, D. L., Connor, D. J., Browne, P. J., Lopez, J. E., & Sabbagh, M. N. (2002). HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer's disease and why it would be ill-advise to use one that crosses the blood-brain barrier. The journal of nutrition, health & aging.
Vancouver
Sparks DL, Connor DJ, Browne PJ, Lopez JE, Sabbagh MN. HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer's disease and why it would be ill-advise to use one that crosses the blood-brain barrier. The journal of nutrition, health & aging. 2002. PMID: 12474023.
BibTeX
@article{sparks2002-12474023,
author = {Sparks, D. L. and Connor, D. J. and Browne, P. J. and Lopez, J. E. and Sabbagh, M. N.},
title = {{HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer's disease and why it would be ill-advise to use one that crosses the blood-brain barrier}},
journal = {The journal of nutrition, health \& aging},
year = {2002},
pmid = {12474023}
}
Related studies in Treatments
Also tagged “double-blind”
783 studies in the library carry the topic tag “double-blind”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 783 tagged studies.