Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: Results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial

D. L. Sparks, D. J. Connor, M. N. Sabbagh, R. B. Petersen, J. Lopez, P. Browne

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Context - Recent evidence suggests that treatment of mild-to-moderate Alzheimer's disease (AD) with atorvastatin provides significant benefit on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) after 6 months. Objective - To determine if benefit on ADAS-cog performance produced by atorvastatin is influenced by severity of cognitive impairment, circulating cholesterol levels, or apolipoprotein E genotype. Design - A double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to atorvastatin calcium or placebo. Setting - A single-site study at the clinical research center of the Sun Health Research Institute. Participants - Ninety-eight individuals with mild-to-moderate AD (MMSE score of 12-28) provided informed consent, and 67 were randomized. Stable dose use of cholinesterase inhibitors, estrogen and vitamin E was allowed, as was the use of many other medications in the treatment of co-morbidities. Participants using cholesterol-lowering medications or being treated for major depression or a psychiatric condition were excluded. Intervention - Once daily atorvastatin calcium (80 mg; two 40 mg tablets) or placebo. Main outcome measures - A primary outcome measure was change ADAS-cog sub-scale score. Secondary outcome measures included scores on the MMSE, and circulating cholesterol levels. The Apolipoprotein E genotype was established for each participant. Results - A significant positive effect on ADAS-cog performance occurred after 6 months of atorvastatin therapy compared with placebo. This positive effect was more prominent among individuals entering the trial with, (i) higher MMSE scores, (ii) cholesterol levels above 200 mg/dl or (iii) if they harbored an apolipoprotein-E-4 allele compared with participants not responding to atorvastatin treatment. Individuals in the placebo group tended to experience more pronounced deterioration if their cholesterol levels exceeded 200 mg/dl or they harbored an apolipoprotein-E-4 allele. Conclusion - Atorvastatin therapy may be of benefit in the treatment of mild-to-moderately affected AD patients, but the level of benefit produced may be predicated on earlier treatment, an individual's apolipoprotein E genotype or whether the patient exhibits elevated cholesterol levels.

Original languageEnglish
Pages (from-to)3-7
Number of pages5
JournalActa Neurologica Scandinavica
Volume114
Issue numberSUPPL. 185
DOIs
StatePublished - Aug 2006

Keywords

  • Alzheimer's disease
  • Atorvastatin calcium
  • Clinical benefit
  • Pharmaco-genetics
  • Treatment trial

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