Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease

Abstract

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.

Interpretation of the evidence for the efficacy and safety of statin therapy

“…In addition, an individual trial that has been specifically designed to assess the effects of a treatment on some particular outcome especially carefully (for example, serial assessments of cognitive function [53][54][55] and of lens opacities [56][57][58] in statin trials) may be more sensitive to any real effects of treatment than would be a meta-analysis based on the less specific assessment of the outcome in all of the other randomized trials -or, to an even greater extent, on non-randomized comparisons involving data recorded for entirely different purposes in observational studies (see below).…”

“…255,259 In a particularly rigorous assessment of effects on cognitive function, 640 patients aged 50-90 with mild-to-moderate Alzheimer's disease were randomized to receive atorvastatin 80 mg daily or placebo for 72 weeks. 55 The co-primary outcomes were Alzheimer's Disease Assessment Scale-cognitive subscale and Alzheimer's Disease Cooperative Study Clinical Global Impression of Change, which were assessed at 3 monthly intervals for 18 months, along with several other measures of cognition at 6 monthly intervals. The results for both of these scores were slightly in favour of statin therapy, with no apparent differences between the treatment groups in any of the other cognitive outcomes assessed, which provides further reassurance.…”

Do Statins Impair Cognition? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…We screened 5,823 citations and evaluated the full text of 1,827 articles, and included 25 RCTs (Table 2) reported in 33 publications. [12][13][14][15] All had placebo rather than standard care comparators. RCTs (reported in 23 publications [13][14][15][36][37][38][39][40][41][42][43][44][45][46][47][48][50][51][52]55,56,62,64 ) enrolled subjects with normal cognition at baseline, four RCTs (reported in seven publications 12,54,[57][58][59][60][61] ) enrolled patients with AD, and three RCTs enrolled other cognitively impaired subjects (traumatic brain injury, 53,63 and neurofibromatosis type 1 49 ).…”

“…The two largest RCTs that contributed the majority of patients (1,046/1,153 or 91 %) were deemed to have low risk of bias. 12,54 Table 3 summarizes study-level assessments for risk of bias. In a random effects meta-analysis, the weighted mean differences for the ADAS-cog and MMSE instruments were higher in the statin compared to no statin arms, suggesting a trend toward benefit, but the 95 % confidence intervals were broad (see Table 4).…”

“…[12][13][14][15] Post-marketing reports (case series of 60 to 171 individuals) have described ill-defined memory impairment, reversible upon statin discontinuation, 1 and some observational studies have described adverse cognitive effects that recurred with re-challenge. 5,8,16 Other reviewers examining RCT and observational study data reported that there is no conclusive evidence that statins cause or contribute to clinically meaningful cognitive impairment, [17][18][19] and may actually provide a slight benefit in dementia prevention.…”