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Review: statins do not protect against development of dementia
Evidence-Based Mental Health, 10/28/09

Haan MN – There is good evidence from two large randomised controlled trials that statins given in late life to individuals at risk of vascular disease are not effective in the prevention of Alzheimer’s disease or dementia.

• Systematic review. Data sources: MEDLINE, EMBASE, The Specialised Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, PsycINFO, CINAHL and LILACS (searched from inception to October 2007), in addition to conference proceedings, theses and ongoing trials.
• Two reviewers independently selected and appraised double blind, randomised, placebo controlled trials comparing any statin with placebo (administered for a minimum of 12 months) in people with normal cognitive function but of sufficient age to be at risk of Alzheimer’s disease (including those at risk of cerebrovascular disease).

• 2 randomised placebo controlled trials were eligible for inclusion: The Medical Research Council/British Heart Foundation funded Heart Protection Study (HPS) 2002 (n = 20 536; age range 40–80 years; 5806 aged >=70 years; 1820 with existing cerebrovascular disease; exclusions: patients with conditions limiting long term compliance; patients with dementia) and PROSPER 2002 (n = 5804; age range 70–82 years; 649 with existing cerebrovascular disease; exclusion: patients with baseline MMSE <24).
• HPS 2002 compared 40 mg simvastatin with matching placebo over a mean of 5 years; PROSPER 2002 compared 40 mg pravastatin with matching placebo over a mean of 3.2 years.
• In HPS 2002, the incidence of dementia did not differ between treatment and placebo groups (both 0.3%) and there was no significant difference between groups in percentage classified as cognitively impaired according to the modified Telephone Interview for Cognitive Status (23.7% simvastatin vs 24.2% placebo).
• Differences remained not significant in subgroup analyses of age and prior history of cerebrovascular accident.
• In PROSPER 2002, there was no difference between groups in change in MMSE score from baseline to study end (difference 0.06, 95% confidence interval –0.04 to 0.16; p = 0.26) or in other cognitive measures (performance on number of correct letter digit codes, words remembered in picture word learning test or time needed to complete the Stroop test).
• At study entry, mean total cholesterol was 5.9 mmol/l and low density lipoprotein (LDL) cholesterol 3.4 mmol/l in HPS 2002 with a mean reduction in LDL cholesterol of 1.0 mmol/l in those treated with simvastatin compared with placebo.
• In PROSPER 2002, mean total cholesterol was 5.7 mmol/l and LDL cholesterol 3.8 mmol/l with mean reduction in LDL cholesterol of 1.03 mmol/l in those treated with pravastatin compared with placebo.

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