Statins for the treatment of Alzheimer's disease

Background

High levels of cholesterol (a fatty substance known as a lipid) in the blood are thought to contribute to the cause of Alzheimer's disease and vascular dementia. The statin family of medications (lovastatin, pravastatin, simvastatin and others) are powerful cholesterol-lowering medications and are first-line treatments for reducing cholesterol in people with, or at risk of, cardiovascular disease. There has been much interest in the possible role of statins in the treatment of dementia.

Study characteristics

Two independent authors searched scientific databases for studies in which a statin or a placebo (a pretend treatment) was given for at least six months. We included people with a probable or possible diagnosis of Alzheimer's disease according to standard clinical criteria. The findings were current to January 2014.

Key results

We identified four studies involving 1154 participants (age range 50 to 90 years). The studies used standard tests to assess the severity of Alzheimer's disease. From these trials, including two large trials, we found no evidence that statins help in the treatment of cognitive decline in dementia.

Quality of the evidence

The quality of evidence is felt to be high as two large randomised controlled trials have been included along with two smaller ones.

Authors' conclusions: 

Analyses from the studies available, including two large randomised controlled trials, indicate that statins have no benefit on the primary outcome measures of ADAS-Cog or MMSE.

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Background: 

The use of statin therapy in established Alzheimer's disease (AD) or vascular dementia (VaD) is a relatively unexplored area. In AD, β-amyloid protein (Aβ) is deposited in the form of extracellular plaques and previous studies have determined Aβ generation is cholesterol dependent. Hypercholesterolaemia has also been implicated in the pathogenesis of VaD. Due to the role of statins in cholesterol reduction, it is biologically plausible they may be efficacious in the treatment of AD and VaD.

Objectives: 

To assess the clinical efficacy and safety of statins in the treatment of AD and VaD. To evaluate if the efficacy of statins in the treatment of AD and VaD depends on cholesterol level, ApoE genotype or cognitive level.

Search strategy: 

We searched ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (20 January 2014).

Selection criteria: 

Double-blind, randomised controlled trials of statins given for at least six months in people with a diagnosis of dementia.

Data collection and analysis: 

Two independent authors extracted and assessed data against the inclusion criteria. We pooled data where appropriate and entered them into a meta-analysis. We used standard methodological procedures expected by The Cochrane Collaboration.

Main results: 

We identified four studies (1154 participants, age range 50 to 90 years). All participants had a diagnosis of probable or possible AD according to standard criteria and most participants were established on a cholinesterase inhibitor. The primary outcome in all studies was change in Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) from baseline. When we pooled data, there was no significant benefit from statin (mean difference -0.26, 95% confidence interval (CI) -1.05 to 0.52, P value = 0.51). All studies provided change in Mini Mental State Examination (MMSE) from baseline. There was no significant benefit from statins in MMSE when we pooled the data (mean difference -0.32, 95% CI -0.71 to 0.06, P value = 0.10). Three studies reported treatment-related adverse effects. When we pooled data, there was no significant difference between statins and placebo (odds ratio 1.09, 95% CI 0.58 to 2.06, P value = 0.78). There was no significant difference in behaviour, global function or activities of daily living in the statin and placebo groups. We assessed risk of bias as low for all studies. We found no studies assessing role of statins in treatment of VaD.

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