Atorvastatin for the treatment of mild to moderate Alzheimer disease: Preliminary results

D. Larry Sparks, Marwan N. Sabbagh, Donald J. Connor, Jean Lopez, Lenore J. Launer, Patrick Browne, Dawn Wasser, Sherry Johnson-Traver, Jeff Lochhead, Chuck Ziolwolski

Research output: Contribution to journalArticlepeer-review

396 Scopus citations


Background: Laboratory evidence of cholesterol-induced production of amyloid β as a putative neurotoxin precipitating Alzheimer disease, along with epidemiological evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder. Objective: To determine if treatment with atorvastatin calcium affects the cognitive and/or behavioral decline in patients with mild to moderate Alzheimer disease. Design: Pilot intention-to-treat, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40-mg tablets) or placebo using last observation carried forward analysis of covariance as the primary method of statistical assessment. Participants: Individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination score of 12-28) were recruited. Of the 98 participants providing informed consent, 71 were eligible for randomization, 67 were randomized, and 63 subjects completed the 3-month visit and were considered evaluable. Main Outcome Measures: The primary outcome measures were change in Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Global Impression of Change Scale scores. The secondary outcome measures included scores on the Mini-Mental State Examination, Geriatric Depression Scale, the Neuropsychiatric Inventory Scale, and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. The tertiary outcome measures included total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels. Results: Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This beneficial effect reached significance for the Geriatric Depression Scale and the Alzheimer's Disease Assessment Scale-cognitive subscale at 6 months and was significant at the level of a trend for the Alzheimer's Disease Assessment Scale-cognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward. Conclusion: Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial.

Original languageEnglish (US)
Pages (from-to)753-757
Number of pages5
JournalArchives of Neurology
Issue number5
StatePublished - May 2005
Externally publishedYes

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology


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