The role of statins in delaying Alzheimer’s disease. Circulating cholesterol levels, ApoE genotype and initial dementia severity influence the level of benefit produced by atorvastatin in mild-to-moderate AD: Results of the ADCLT

Previous epidemiological studies have suggested that prior statin use may reduce the risk of developing AD later in life. More recent incidence studies question the link between statin use and reduced risk of AD. We have shown that atorvastatin treatment produced significantly (p< 0.004) improved performance on cognition and memory after 6 months of treatment (ADAS-cog) among patients with mild-to-moderate AD. This superior effect persisted at one-year (p= 0.055). Evidence also suggests that atorvastatin may slow the progression of mild-to-moderate AD, thereby prolonging the quality of an afflicted individual's life. To determine if the clinical benefit of atorvastatin treatment on ADAS-cog performance compared to placebo in mild-to-moderate AD is influenced by severity of cognitive impairment, circulating cholesterol levels, or Apolipoprotein E genotype. This was a double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to once daily atorvastatin calcium (80 mg; two 40mg tablets) or placebo among individuals with mild-to-moderate AD (MMSE score of 12-28). Stable dose use of cholinesterase inhibitors, estrogen and vitamin E was allowed, as was the use of most 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. Of the 98 participants providing Informed Consent, 67 were randomized and 63 were evaluable. A primary outcome measure was change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) sub-scale score. Secondary outcome measures included scores on the MMSE, circulating cholesterol levels and Apolipoprotein E genotype. Atorvastatin produced a significant positive effect on the ADAS-cog performance after 6-months of treatment. This positive effect was more prominent among individuals entering the trial with, 1) higher MMSE scores, 2) cholesterol levels above 200 mg/dL or 3) if they harbored an ApoE-4 allele. Individuals in the placebo group tended to perform worse if their cholesterol levels were above 200 mg/dL or they harbored an ApoE-4 allele. Accordingly, 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, ApoE genotype or whether the patient exhibits elevated cholesterol levels.