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


METHODS
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.
Feldman
H H
HH
Division of Neurology, University of British Columbia, UBCH Clinic for Alzheimer's Disease and Related Disorders, Vancouver, Canada. hfeldman@interchange.ubc.ca
Doody
R S
RS
Kivipelto
M
M
Sparks
D L
DL
Waters
D D
DD
Jones
R W
RW
Schwam
E
E
Schindler
R
R
Hey-Hadavi
J
J
DeMicco
D A
DA
Breazna
A
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D011758:Pyrroles / Q000627:therapeutic use*
D008078:Cholesterol, LDL; D018680:Cholinergic Antagonists; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin