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Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial
Sparks DL, Connor DJ, Sabbagh MN, Petersen RB, Lopez J, Browne P.. Acta neurologica Scandinavica. Supplementum, 2006-01-01
Topic: Amyloid, tau and blood-test diagnosis
Context Recent evidence suggests that treatment of mild-to-moderate Alzheimer's disease (AD) with atorvastatin provides significant benefit on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) after 6 months. Objective To determine if benefit on ADAS-cog performance produced by atorvastatin is influenced by severity of cognitive impairment, circulating cholesterol levels, or apolipoprotein E genotype. Design A double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to atorvastatin calcium or placebo. Setting A single-site study at the clinical research center of the Sun Health Research Institute. Participants Ninety-eight individuals with mild-to-moderate AD (MMSE score of 12-28) provided informed consent, and 67 were randomized. Stable dose use of cholinesterase inhibitors, estrogen and vitamin E was allowed, as was the use of many other medications in the treatment of co-morbidities. Participants using cholesterol-lowering medications or being treated for major depression or a psychiatric condition were excluded. Intervention Once daily atorvastatin calcium (80 mg; two 40 mg tablets) or placebo. Main outcome measures A primary outcome measure was change ADAS-cog sub-scale score. Secondary outcome measures included scores on the MMSE, and circulating cholesterol levels. The Apolipoprotein E genotype was established for each participant. Results A significant positive effect on ADAS-cog performance occurred after 6 months of atorvastatin therapy compared with placebo. This positive effect was more prominent among individuals entering the trial with, (i) higher MMSE scores, (ii) cholesterol levels above 200 mg/dl or (iii) if they harbored an apolipoprotein-E-4 allele compared with participants not responding to atorvastatin treatment. Individuals in the placebo group tended to experience more pronounced deterioration if their cholesterol levels exceeded 200 mg/dl or they harbored an apolipoprotein-E-4 allele. Conclusion Atorvastatin therapy may be of benefit in the treatment of mild-to-moderately affected AD patients, but the level of benefit produced may be predicated on earlier treatment, an individual's apolipoprotein E genotype or whether the patient exhibits elevated cholesterol levels.
Key findings
- Context Recent evidence suggests that treatment of mild-to-moderate Alzheimer's disease (AD) with atorvastatin provides significant benefit on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) after 6 months.
- Results A significant positive effect on ADAS-cog performance occurred after 6 months of atorvastatin therapy compared with placebo.
- This positive effect was more prominent among individuals entering the trial with, (i) higher MMSE scores, (ii) cholesterol levels above 200 mg/dl or (iii) if they harbored an apolipoprotein-E-4 allele compared with participants not responding to atorvastatin treatment.
Why it matters
In this 1-year trial of 67 randomized participants with mild-to-moderate Alzheimer disease, atorvastatin showed a significant positive effect on ADAS-cog performance after 6 months compared with placebo. This effect was more prominent among those entering the trial with higher MMSE scores and cholesterol levels above 200 mg/dl.
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Study details
- Evidence strengthHigh
How this study scored 60/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neurologica Scandinavica. Supplementum) |
| Journal's citation record | 2 / 4 | Acta Neurologica Scandinavica: journal h-index 160 (OpenAlex, 2026-10-29) |
| 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 | 2006 — 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 | 5 / 7 | Cited 131 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.0 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 3 / 6 | Cited 6.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Patrick J Browne: h-index 30 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Case Western Reserve University: institution h-index 1,159 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16866904) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 60 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Sparks, D. L., Connor, D. J., Sabbagh, M. N., Petersen, R. B., Lopez, J., & Browne, P. (2006). Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial. Acta neurologica Scandinavica. Supplementum. https://doi.org/10.1111/j.1600-0404.2006.00690.x
Vancouver
Sparks DL, Connor DJ, Sabbagh MN, Petersen RB, Lopez J, Browne P. Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial. Acta neurologica Scandinavica. Supplementum. 2006. doi:10.1111/j.1600-0404.2006.00690.x. PMID: 16866904.
BibTeX
@article{sparks2006-16866904,
author = {Sparks, D. L. and Connor, D. J. and Sabbagh, M. N. and Petersen, R. B. and Lopez, J. and Browne, P.},
title = {{Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial}},
journal = {Acta neurologica Scandinavica. Supplementum},
year = {2006},
doi = {10.1111/j.1600-0404.2006.00690.x},
pmid = {16866904},
url = {https://doi.org/10.1111/j.1600-0404.2006.00690.x}
}
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