Pravastatin and cognitive function in the elderly. Results of the PROSPER study

Trompet, Stella; Vliet, Peter Van de; Craen, Anton J. M. de; Jolles, Jelle; Buckley, Brendan M.; Murphy, Michael B.; Ford, Ian; Macfarlane, Peter W.; Sattar, Naveed; Packard, Chris J.; Stott, David J.; Shepherd, John R. A.; Bollen, E.; Blauw, Gerard J.; Jukema, J. Wouter; Westendorp, Rudi G. J.

doi:10.1007/s00415-009-5271-7

Cited by 237 publications

(157 citation statements)

References 20 publications

(19 reference statements)

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“…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).…”

Section: Value Of Meta-analyses Of Randomized Trialsmentioning

confidence: 99%

“…In particular, cognitive measures were carefully assessed among the 5804 patients aged 70-82 years who were randomly allocated pravastatin 40 mg daily or placebo for an average of 3.2 years in the PROSPER trial. 53,54 At baseline and then annually, the mini mental state examination and a battery of psychometric tests (i.e. picture-word learning test, Stroop colour word test, and letter digit coding test) were administered.…”

Section: Memory and Other Aspects Of Cognitionmentioning

confidence: 99%

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

et al. 2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms SummaryThis review is intended to help clinicians, patients and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomized controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment.Large-scale randomized trial evidence shows that statin therapy reduces the risk of heart attacks, ischaemic strokes and coronary revascularization procedures ("major vascular events") by about one quarter for each mmol/L reduction in low density lipoprotein (LDL) cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (e.g. atorvastatin 40 mg daily, costing about £2 per

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Section: Value Of Meta-analyses Of Randomized Trialsmentioning

confidence: 99%

Section: Memory and Other Aspects Of Cognitionmentioning

confidence: 99%

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

et al. 2016

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“…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 ).…”

Section: Assessment Of Heterogeneity and Meta-regression Analysesmentioning

confidence: 99%

“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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BACKGROUND:In 2012, the United States Food and Drug Administration (FDA) issued a warning regarding potential adverse effects of HMG-CoA reductase inhibitors (statins) on cognition, based on the Adverse Events Reporting System and a review of the medical literature. We aimed to synthesize randomized clinical trial (RCTs) evidence on the association between statin therapy and cognitive outcomes. METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL through December 2012, and reviewed published systematic reviews of statin treatment. We sought RCTs that compared statin treatment versus placebo or standard care, and reported at least one cognitive outcome (frequency of adverse cognitive events or measurements using standard neuropsychological cognitive test scores). Studies reporting sufficient information to calculate effect sizes were included in metaanalyses. Standardized and unstandardized mean differences were calculated for continuous outcomes for global cognition and for pre-specified cognitive domains. The main outcome was change in cognition measured by neuropsychological tests; an outcome of secondary interest was the frequency of adverse cognitive events observed during follow-up. RESULTS: We identified 25 RCTs (all placebo-controlled) reporting cognitive outcomes in 46,836 subjects, of which 23 RCTs reported cognitive test results in 29,012 participants. Adverse cognitive outcomes attributable to statins were rarely reported in trials involving cognitively normal or impaired subjects. Furthermore, meta-analysis of cognitive test data (14 studies; 27,643 participants) failed to show significant adverse effects of statins on all tests of cognition in either cognitively normal subjects (standardized mean difference 0.01, 95 % confidence interval, CI, −0.01 to 0.03, p=0.42) or Alzheimer's disease subjects (standardized mean difference −0.05, 95 % CI −0.19 to 0.10, p=0.38). CONCLUSIONS: Statin therapy was not associated with cognitive impairment in RCTs. These results raise questions regarding the continued merit of the FDA warning about potential adverse effects of statins on cognition.

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“…All three of these trials focused on subjects with AD. The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial also showed that pravastatin had no significant effect on cognitive function in the elderly [14]. Clinical trial data on subjects with MCI do not exist.…”

Section: Introductionmentioning

confidence: 99%

P2‐028: The Effect of Statins on Rate of Cognitive Decline in Mild Cognitive Impairment

Smith

Kang

Sabbagh

2016

Alzheimer's & Dementia

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Introduction: This study's aims are to identify whether a relationship between statin use and rate of cognitive decline exists. The relationship between statins and mild cognitive impairment (MCI) has been investigated in the past with the evidence showing mixed results. Methods: Seven hundred sixty-eight subjects were identified with MCI. Subjects were stratified into six possible groups according to apolipoprotein E (APOE) ε4 allele status and statin use and assessed for decline in cognitive function.Results: All cognitive assessments trended toward less decline with statin use. Alzheimer's Disease Assessment Scale 11 (ADAS 11) showed the biggest difference in mean change between statin users and nonusers (20.82 vs. 21.22, respectively). Change reached marginal significance on the ADAS 11 when stratified by APOE ε4-negative subjects. Discussion: All cognitive assessments trended toward less decline when subjects were concurrently treated with a statin, supporting the position that statins do not have a net negative effect on cognitive assessment and suggesting a potential treatment benefit.

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Pravastatin and cognitive function in the elderly. Results of the PROSPER study

Cited by 237 publications

References 20 publications

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

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

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

P2‐028: The Effect of Statins on Rate of Cognitive Decline in Mild Cognitive Impairment

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