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Assessing Statins for Alzheimer Disease: Conflicting Evidence

(PSYCHIATRIC TIMES) - he second report from the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial was recently published, along with several reviews of clinical and laboratory investigations of the statins, in a theme issue of Acta Neurologica Scandinavica. The accumulated data reflect the potential of the agents to affect the onset or course of Alzheimer disease (AD), with contradictory or insufficient evidence of treatment effect.

The first ADCLT report suggested that lowering cholesterol levels with atorvastatin (Lipitor) could reduce cognitive and behavioral deterioration in persons with mild to moderate AD.1 This second report examined whether the apparent benefit is influenced by severity of cognitive impairment, circulating cholesterol levels, or apolipoprotein E genotype.2

The ADCLT trial is a double-blind controlled study involving 67 patients with mild to moderate AD, randomized to receive 1 year of treatment with atorvastatin (80 mg/d) or placebo. The primary measure is scoring on the Alzheimer's Disease Assessment Scale–Cognitive (ADAS-cog) subscale, with secondary measurement on the Mini-Mental State Examination (MMSE). Prestudy medications for both AD and comorbidities continued throughout the study period.

Both the statin treatment and placebo groups showed deterioration on the ADAS-cog at 3 months, and the placebo group continued to deteriorate by about 1 point per quarter throughout the study period. The ADAS-cog mean score in the statin treatment group was about 3.5 points higher than the mean score of the placebo group at 6 months. The ADCLT investigators reported that the benefit of the statins appeared to be more prominent in those with cholesterol levels above 200 mg/dL, those with the apoE4 allele, and those with higher baseline MMSE scores.

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