The Atorvastatin/Donepezil in Alzheimer’s Disease Study (LEADe): Design and baseline characteristics^⁎

Abstract 

Background

Growing evidence suggests that elevated cholesterol levels in mid-life are associated with increased risk of developing Alzheimer’s disease (AD), and that statins might have a protective effect against AD and dementia. The Lipitor’s Effect in Alzheimer’s Dementia (LEADe) study tests the hypothesis that a statin (atorvastatin 80 mg daily) will provide a benefit on the course of mild to moderate AD in patients receiving background therapy of a cholinesterase inhibitor (donepezil 10 mg daily).

Methods

This is an international, multicenter, double-blind, randomized, parallel-group study with a double-blind randomized withdrawal phase of patients with mild to moderate AD (Mini-Mental State Examination [MMSE] score, 13 to 25). Inclusion criteria included age 50 to 90 years, receiving donepezil 10 mg for at least 3 months before randomization, and low-density lipoprotein cholesterol levels (LDL-C) 2.5 to 3.5 mmol/L (95 to 195 mg/dL). Co-primary end points are changes in AD Assessment Scale-cognitive subscale (ADAS-cog) and AD Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale scores. A confirmatory end point is rate of change in whole brain and hippocampal volumes in patients who enrolled in the magnetic resonance imaging substudy.

Results

Enrollment of 641 subjects is complete. The baseline mean data are age 74 ± 8 years, 53% women, MMSE 22 ± 3, ADAS-cog 23 ± 10, AD Functional Assessment and Change Scale (ADFACS) 13 ± 9, Neuropsychiatric Inventory (NPI) 10 ± 11, and Clinical Dementia Rating-Sum of Boxes (CDR-SB) 6 ± 3. Mean prior donepezil treatment was 409 ± 407 days. Mean baseline lipid levels are total cholesterol 5.8 ± 0.8 mmol/L (224 ± 33 mg/dL), LDL-C 3.7 ± 0.7 mmol/L (143 ± 26 mg/dL), triglycerides 1.5 ± 0.7 mmol/L (132 ± 64 mg/dL), and high-density lipoprotein cholesterol 1.6 ± 0.5 mmol/L (64 ± 18 mg/dL).

Conclusions

LEADe will report in 2008 and is expected to provide a more definitive evaluation of the potential for statins in the treatment of people with AD.

Keywords: Alzheimer’s disease, Randomized clinical trial, Drug treatment, Atorvastatin, Donepezil

• ⁎ Roy W. Jones and Miia Kivipelto contributed equally to the content of the manuscript.