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Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe.

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.

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  • Authors+Show Affiliations

    ,

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

    , , , , , , , , , ,

    Source

    Neurology 74:12 2010 Mar 23 pg 956-64

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Atorvastatin Calcium
    Cholesterol, LDL
    Cholinergic Antagonists
    Double-Blind Method
    Female
    Heptanoic Acids
    Hippocampus
    Humans
    Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Magnetic Resonance Imaging
    Male
    Middle Aged
    Organ Size
    Pyrroles

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    20200346

    Citation

    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 ER -