There good evidence that statins given in late life to individuals at risk of vascular disease have no effect in preventing dementia

McGuinness B, Craig D, Bullock R, Passmore P

Published Online:

April 15, 2009

Evidence accumulating from biological and epidemiological studies suggest that high levels of serum cholesterol may promote the pathological processes that lead to Alzheimer's disease. Lowering cholesterol in experimental animal models slows the expression of Alzheimer's pathology. These findings raise the possibility that treating humans with cholesterol lowering medications might reduce the risk of developing Alzheimer's disease. The statin family of medications (lovastatin, pravastatin,simvastatin, and others) are powerful cholesterol lowering agents of proven benefit in vascular disease. Several clinical studies comparing the occurrence of Alzheimer's disease between users of statins and non-users of statins suggest that risk of Alzheimer's disease is substantially reduced among the users. However, because these studies are not randomized trials, they provide insufficient evidence to recommend statin therapy. Two randomized trials have since been carried out and neither showed any reduction in occurrence of AD or dementia in patients treated with statins compared to those given placebo. Statins cannot therefore be recommended for the prevention of AD or dementia.

Abstract (click to read)

Background:

This is an update of a Cochrane review first published in 2001. At that stage there was insufficient evidence to recommend statins for the prevention of Alzheimer's disease (AD). The scope of this review has been expanded to include all forms of dementia.

Objectives:

To assess the effects of statins in the prevention of dementia.

Search strategy:

The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 10 October 2007 using the terms statin*, lovastatin*, pravastatin*, simvastatin*, fluvastatin*, atorvastatin* and rosuvastatin*. The CDCIG Register contains records from many healthcare databases, SIGLE, LILACS as well as many trials databases and is updated regularly.

Selection criteria:

Double-blind randomized placebo-controlled trials of statins in people at risk of AD and dementia.

Data collection and analysis:

Two independent reviewers extracted and assessed data independently and agreement was reached after discussion. Adverse effects were noted.

Main results:

Two trials were identified with 26,340 participants; HPS 2002 and PROSPER 2002. Age range was 40-82 years across the two studies, PROSPER 2002 included 5804 patients aged 70-82 years and HPS included 20,536 patients with 5806 at least 70 years old at study entry. Mean total cholesterol 5.9 mmol/l, LDL cholesterol 3.4mmol/l at study entry with mean reduction in LDL cholesterol of 1.0mmol/l in simvastatin treated patients compared to placebo in HPS 2002. Mean total cholesterol 5.7mmol/l, LDL cholesterol 3.8 mmol/l at study entry with mean reduction in LDL cholesterol of 1.02 mmol/l in pravastatin treated patients compared to placebo in PROSPER 2002. Mean follow-up 3.2 years in PROSPER, 5 years in HPS 2002. Cognition was measured at different times and with different scales so could not be combined in a meta-analysis. There was no difference in incidence of dementia in HPS 2002 (31 cases in simvastatin group, 31 cases in placebo group) nor in performance on the modified Telephone Interview for Cognitive Status at final follow-up (23.7% simvastatin group cognitively impaired vs 24.2% in placebo group). There was no difference in cognition between groups either in relation to age at study entry or previous history of cerebrovascular disease. Cognitive function declined at the same rate in both treatment groups in PROSPER 2002, there was no significant difference between pravastatin treated and placebo groups in performance on letter digit codes, picture word learning test, Stroop and Mini Mental State Examination. There was no evidence that statins were detrimental to cognition.

Authors' conclusions:

There is good evidence from RCTs that statins given in late life to individuals at risk of vascular disease have no effect in preventing AD or dementia. Biologically it seems feasible that statins could prevent dementia due to their role in cholesterol reduction and initial evidence from observational studies was very promising. Indication bias may have been a factor in these studies however and the evidence from subsequent RCTs has been negative.

This record should be cited as:

McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD003160. DOI: 10.1002/14651858.CD003160.pub2

Assessed as up to date:

November 7, 2008

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Primary Review Group:

Dementia and Cognitive Improvement Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

Do statins prevent dementia?

Bottom line:

There is good evidence statins given in late life to individuals at risk of vascular disease have no effect in preventing Alzheimer's disease (AD) and dementia. The age range of participants was 40-82 years across the 2 studies.

Caveat:

Cognition was measured at different times and with different scales in the 2 studies so could not be combined in a metaanalysis. The mean follow-up period was 3.2 years in 1 study and 5 years in the other.

Context:

PAD is the most common form of dementia affecting up to 15 million individuals worldwide. AD has a prevalence of approximately 1% among 60 to 64-year-olds, rising to 40% in those age 85 years and older. Biologically it seems feasible statins could prevent dementia due to their role in cholesterol reduction and initial evidence from observational studies was very promising.

Cochrane Systematic Review:

McGuinness B et al. Statins for the prevention of dementia. Cochrane Reviews 2009, Issue 2. Article No. CD003160. DOI: 10.1002/14651858.CD003160.pub2. This review contains 2 studies involving 26,340 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Mental health > Dementia & cognition > Interventions aimed at interrupting disease processes

Mental health > Dementia & cognition > Prevention: non-cognitively impaired

Neurology > Dementia & cognition > Interventions aimed at interrupting disease processes

Neurology > Dementia & cognition > Prevention: non-cognitively impaired

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

There good evidence that statins given in late life to individuals at risk of vascular disease have no effect in preventing dementia

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