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.
MeSH
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&pmid=20200346
DB - PRIME
DP - Unbound Medicine
ER -
