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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.
Acta Neurol Scand Suppl 2006; 185:3-7AN

Abstract

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.

Authors+Show Affiliations

Sun Health Research Institute, Sun City, AZ 85351, USA. larry.sparks@sunhealth.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16866904

Citation

Sparks, D L., et al. "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, vol. 185, 2006, pp. 3-7.
Sparks DL, Connor DJ, Sabbagh MN, et al. 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 Neurol Scand, Suppl. 2006;185:3-7.
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, 185, pp. 3-7.
Sparks DL, et al. 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 Neurol Scand, Suppl. 2006;185:3-7. PubMed PMID: 16866904.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Sparks,D L, AU - Connor,D J, AU - Sabbagh,M N, AU - Petersen,R B, AU - Lopez,J, AU - Browne,P, PY - 2006/7/27/pubmed PY - 2006/10/3/medline PY - 2006/7/27/entrez SP - 3 EP - 7 JF - Acta neurologica Scandinavica. Supplementum JO - Acta Neurol. Scand., Suppl. VL - 185 N2 - 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. SN - 0065-1427 UR - https://www.unboundmedicine.com/medline/citation/16866904/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_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0065-1427&date=2006&volume=185&issue=&spage=3 DB - PRIME DP - Unbound Medicine ER -