The Atorvastatin/Donepezil in Alzheimer's Disease Study (LEADe): Design and baseline characteristics^**Roy W. Jones and Miia Kivipelto contributed equally to the content of the manuscript.

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.