The Effect of HMG-CoA Reductase Inhibitors on Cognition in Patients With Alzheimer's Dementia: A Prospective Withdrawal and Rechallenge Pilot Study

Abstract

BackgroundStatins are well-known for their cardiovascular benefits. However, the cognitive effects of statins are not well understood. We hypothesized that individuals with preexisting dementia would be more vulnerable to statin-related cognitive effects. ObjectiveThe aim of this study was to evaluate the impact on cognition of 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitor (statin) discontinuation and rechallenge in individuals with Alzheimer's dementia (AD) on statins at baseline. MethodsA 12-week prospective, open-label study was conducted in a geriatric clinic setting. Eighteen older subjects underwent a 6-week withdrawal phase of statins followed by a 6-week rechallenge. The primary outcome measure was cognition, measured by the Mini-Mental State Examination (MMSE); secondary outcome measures were the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and fasting cholesterol. The change in outcome measures was assessed using repeated-measures ANOVA and paired t tests. ResultsAt the end of the intervention, there was a significant difference across time for MMSE score (P = 0.018), and total cholesterol (P = 0.0002) and a trend toward change across time for ADL (P = 0.07) and IADL (P = 0.06) scale scores. Further analyses using paired t tests indicated improvement in MMSE scores (Δ1.9 [3.0], P = 0.014) with discontinuation of statins and a decrease in MMSE scores (Δ1.9 [2.7], P = 0.007) after rechallenge. Total cholesterol increased with statin discontinuation (P = 0.0003) and decreased with rechallenge (P = 0.0007). The CERAD score did not show a change across time (P = 0.31). There was a trend toward improvement in ADL (P = 0.07) and IADL (P = 0.06) scale scores with discontinuation of statins, but no change with rechallenge. ConclusionsThis pilot study found an improvement in cognition with discontinuation of statins and worsening with rechallenge. Statins may adversely affect cognition in patients with dementia.