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


Feldman, H. H., Doody, R. S., Kivipelto, M., Sparks, D. L., Waters, D. D., Jones, R. W., Schwam, E., Schindler, R., Hey-Hadavi, J., DeMicco, D. A., Breazna, A.


Neurology, Volume: 74, No.: 12, Pages.: 956-964

Year of Publication



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.;

Bibtex Citation

@article{Feldman_2010, doi = {10.1212/wnl.0b013e3181d6476a}, url = {}, year = 2010, month = {mar}, publisher = {Ovid Technologies (Wolters Kluwer Health)}, volume = {74}, number = {12}, pages = {956--964}, author = {H. H. Feldman and R. S. Doody and M. Kivipelto and D. L. Sparks and D. D. Waters and R. W. Jones and E. Schwam and R. Schindler and J. Hey-Hadavi and D. A. DeMicco and A. Breazna}, title = {Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: {LEADe}}, journal = {Neurology} }


aged, aged, 80 and over, alzheimer disease, atorvastatin, cholesterol ldl, cholinergic antagonists, double-blind method, drug effects, drug therapy, female, heptanoic acids, hippocampus, humans, magnetic resonance imaging, male, metabolism, middle aged, organ size, pathology, pyrroles, therapeutic use

Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes

Cognition, Physical Health

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions