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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 ≥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.
Glossary
- AchEI=
- acetylcholinesterase inhibitor;
- AD=
- Alzheimer disease;
- ADAS-Cog=
- Alzheimer's Disease Assessment Scale-Cognitive Subscale;
- ADCS-CGIC=
- Alzheimer's Disease Cooperative Study Clinical Global Impression of Change;
- ADFACS=
- Alzheimer's Disease Functional Assessment and Change Scale;
- ANCOVA=
- analysis of covariance;
- APP=
- amyloid precursor protein;
- BSI=
- boundary shift integral;
- CDR-SB=
- Clinical Dementia Rating-Sum of Boxes;
- LDL-C=
- low-density lipoprotein cholesterol;
- LOCF=
- last observation carried forward;
- LS=
- least-squares;
- MITT=
- modified intent-to-treat population;
- MMSE=
- Mini-Mental State Examination;
- NPI=
- Neuropsychiatric Inventory;
- RCT=
- randomized controlled trial;
- SAE=
- serious adverse event.
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