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Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe.
Neurology 2010; 74(12):956-64Neur

Abstract

BACKGROUND

There is some evidence that statins may have a protective and symptomatic benefit in Alzheimer disease (AD). The LEADe study is a randomized controlled trial (RCT) evaluating the efficacy and safety of atorvastatin in patients with mild to moderate AD.

METHODS

This was an international, multicenter, double-blind, randomized, parallel-group study. Subjects had mild to moderate probable AD (Mini-Mental State Examination score 13-25), were aged 50-90 years, and were taking donepezil 10 mg daily for > or 3 months prior to screening. Entry low-density lipoprotein cholesterol levels (LDL-C) were > 95 and < 195 mg/dL. Patients were randomized to atorvastatin 80 mg/day or placebo for 72 weeks followed by a double-blind, 8-week atorvastatin withdrawal phase. Coprimary endpoints were changes in cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog]) and global function (Alzheimer's Disease Cooperative Study Clinical Global Impression of Change [ADCS-CGIC]) at 72 weeks.

RESULTS

A total of 640 patients were randomized in the study. There were no significant differences in the coprimary endpoints of ADAS-cog or ADCS-CGIC or the secondary endpoints. Atorvastatin was generally well-tolerated.

CONCLUSIONS

In this large-scale randomized controlled trial evaluating statin therapy as a treatment for mild to moderate Alzheimer disease, atorvastatin was not associated with significant clinical benefit over 72 weeks. This treatment was generally well-tolerated without unexpected adverse events.

CLASSIFICATION OF EVIDENCE

This study provides Class II evidence that intensive lipid lowering with atorvastatin 80 mg/day in patients with mild to moderate probable Alzheimer disease (aged 50-90), taking donepezil, with low-density lipoprotein cholesterol levels between 95 and 195 mg/dL over 72 weeks does not benefit cognition (as measured by Alzheimer's Disease Assessment Scale-Cognitive Subscale) (p = 0.26) or global function (as measured by Alzheimer's Disease Cooperative Study Clinical Global Impression of Change) (p = 0.73) compared with placebo.

Authors+Show Affiliations

Division of Neurology, University of British Columbia, UBCH Clinic for Alzheimer's Disease and Related Disorders, Vancouver, Canada. hfeldman@interchange.ubc.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20200346

Citation

Feldman, H H., et al. "Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease: LEADe." Neurology, vol. 74, no. 12, 2010, pp. 956-64.
Feldman HH, Doody RS, Kivipelto M, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010;74(12):956-64.
Feldman, H. H., Doody, R. S., Kivipelto, M., Sparks, D. L., Waters, D. D., Jones, R. W., ... Breazna, A. (2010). Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology, 74(12), pp. 956-64. doi:10.1212/WNL.0b013e3181d6476a.
Feldman HH, et al. Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease: LEADe. Neurology. 2010 Mar 23;74(12):956-64. PubMed PMID: 20200346.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. AU - Feldman,H H, AU - Doody,R S, AU - Kivipelto,M, AU - Sparks,D L, AU - Waters,D D, AU - Jones,R W, AU - Schwam,E, AU - Schindler,R, AU - Hey-Hadavi,J, AU - DeMicco,D A, AU - Breazna,A, AU - ,, Y1 - 2010/03/03/ PY - 2010/3/5/entrez PY - 2010/3/5/pubmed PY - 2010/4/7/medline SP - 956 EP - 64 JF - Neurology JO - Neurology VL - 74 IS - 12 N2 - BACKGROUND: There is some evidence that statins may have a protective and symptomatic benefit in Alzheimer disease (AD). The LEADe study is a randomized controlled trial (RCT) evaluating the efficacy and safety of atorvastatin in patients with mild to moderate AD. METHODS: This was an international, multicenter, double-blind, randomized, parallel-group study. Subjects had mild to moderate probable AD (Mini-Mental State Examination score 13-25), were aged 50-90 years, and were taking donepezil 10 mg daily for > or 3 months prior to screening. Entry low-density lipoprotein cholesterol levels (LDL-C) were > 95 and < 195 mg/dL. Patients were randomized to atorvastatin 80 mg/day or placebo for 72 weeks followed by a double-blind, 8-week atorvastatin withdrawal phase. Coprimary endpoints were changes in cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog]) and global function (Alzheimer's Disease Cooperative Study Clinical Global Impression of Change [ADCS-CGIC]) at 72 weeks. RESULTS: A total of 640 patients were randomized in the study. There were no significant differences in the coprimary endpoints of ADAS-cog or ADCS-CGIC or the secondary endpoints. Atorvastatin was generally well-tolerated. CONCLUSIONS: In this large-scale randomized controlled trial evaluating statin therapy as a treatment for mild to moderate Alzheimer disease, atorvastatin was not associated with significant clinical benefit over 72 weeks. This treatment was generally well-tolerated without unexpected adverse events. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that intensive lipid lowering with atorvastatin 80 mg/day in patients with mild to moderate probable Alzheimer disease (aged 50-90), taking donepezil, with low-density lipoprotein cholesterol levels between 95 and 195 mg/dL over 72 weeks does not benefit cognition (as measured by Alzheimer's Disease Assessment Scale-Cognitive Subscale) (p = 0.26) or global function (as measured by Alzheimer's Disease Cooperative Study Clinical Global Impression of Change) (p = 0.73) compared with placebo. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/20200346/full_citation L2 - http://www.neurology.org/cgi/pmidlookup?view=long&amp;pmid=20200346 DB - PRIME DP - Unbound Medicine ER -