Effects of treatment with simvastatin and pravastatin on cognitive function in patients with hypercholesterolaemia.

Cutler, N.R.; Sramek, John J.; Veroff, Amy E.; Block, Gilbert A.; Stauffer, Laura; Lines, Christopher

doi:10.1111/j.1365-2125.1995.tb04458.x

Cited by 40 publications

(19 citation statements)

References 13 publications

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“…This in turn suggests the possibility of premature cognitive decline by patients subjected to chronic stain treatment (Muldoon et al, 2004). In this regard, although prospective studies to date have failed to demonstrate a causal relationship between statin use and dementia (Wagstaff et al, 2003), the co-morbidities of hypercholesterolemic patients requiring chronic statin use might obscure such a relationship, while the time frames of these studies may have been too short for such an association to become manifest in any event (Cutler et al, 1995;Golomb et al, 2004). In this context, our results suggest the need for awareness of the possible toxicities accruing to long-term stain use, and identify one such potential toxicity, the premature differentiation and attendant long-term depletion of oligodendrocyte progenitor cells of the adult brain.…”

Section: Discussionmentioning

confidence: 89%

Statin treatment of adult human glial progenitors induces PPARγ‐mediated oligodendrocytic differentiation

Sim

Lang

Ali

et al. 2008

Glia

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The statins have been proposed as possible therapeutic agents for a variety of autoimmune disorders, including multiple sclerosis. In a genomic screen, we found that glial progenitor cells (GPCs) of the adult human white matter expressed significant levels of the principal statin target, HMG-CoA reductase, as well as additional downstream members of the sterol synthesis pathway. We therefore asked if statin treatment might influence the differentiated fate of adult glial progenitor cells. To assess the functional importance of the sterol synthesis pathway to adult human glial progenitors, we used simvastatin or pravastatin to inhibit HMG-CoA reductase, and then assessed the phenotypic differentiation of the progenitors, as well as the molecular concomitants thereof. We found that both statins induced a dose-dependent induction of oligodendrocyte phenotype, and concomitant reduction in progenitor number. Oligodendrocyte commitment was associated with induction of the sterol-regulated nuclear co-receptor PPARgamma, and could be blocked by the specific PPARgamma antagonist GW9662. Thus, statins may promote oligodendrocyte lineage commitment by parenchymal glial progenitor cells; this might reduce the available progenitor pool, and hence degrade the long-term regenerative competence of the adult white matter.

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Section: Discussionmentioning

confidence: 89%

Statin treatment of adult human glial progenitors induces PPARγ‐mediated oligodendrocytic differentiation

Sim

Lang

Ali

et al. 2008

Glia

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“…[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 ). Simvastatin (eight trials), pravastatin (eight trials), and lovastatin (six trials) were most frequently utilized in the statin RCTs.…”

Section: Assessment Of Heterogeneity and Meta-regression Analysesmentioning

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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“…In addition, although rare instances of statinassociated memory loss have been described (53), animal studies have indicated that the concentrations needed for memory impairment are generally much higher than the dose normally used in cholesterol-lowering therapy (31). Furthermore, various clinical trials have reported no significant effects of statins on cognitive performance (54)(55)(56)(57). Finally, it is worth noting that statins tend to increase serum plant sterol and stanol levels (58), which makes individuals on statin treatment an excellent population to study the effects of plant sterols and stanols.…”

Section: Discussionmentioning

confidence: 98%

Consuming Functional Foods Enriched with Plant Sterol or Stanol Esters for 85 Weeks Does Not Affect Neurocognitive Functioning or Mood in Statin-Treated Hypercholesterolemic Individuals

Schiepers

Groot

Boxtel

et al. 2009

The Journal of Nutrition

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Recent animal and human studies have shown that plant sterols and stanols, which are used as functional food ingredients to lower increased LDL cholesterol concentrations, pass the blood-brain barrier. Whether this affects neurocognitive functioning and mental well-being in humans has, to our knowledge, never been investigated. The aim of the present study was therefore to examine the effects of long-term plant sterol or stanol consumption on neurocognitive functioning and mood in a randomized, double-blind, placebo-controlled dietary intervention trial. To this end, hypercholesterolemic individuals, aged 43-69 y, receiving stable statin treatment were randomly assigned to an 85-wk supplementation with margarines enriched with plant sterol esters (2.5 g/d), plant stanol esters (2.5 g/d), or placebo. At baseline and at the end of the intervention period, all participants underwent a cognitive assessment. In addition, subjective cognitive functioning and mood were assessed by means of questionnaires (Cognitive Failure Questionnaire and depression subscale of the Symptom Checklist 90, respectively). Long-term supplementation with plant sterol or stanol esters did not affect cognitive performance (memory, simple information processing speed, complex information processing speed, Letter-Digit Substitution test performance), subjective cognitive functioning, or mood. In conclusion, the present results indicate that long-term use of plant sterols or stanols at recommended intakes of 2.5 g/d does not affect neurocognitive functioning or mood in hypercholesterolemic individuals receiving statin treatment.

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Effects of treatment with simvastatin and pravastatin on cognitive function in patients with hypercholesterolaemia.

Cited by 40 publications

References 13 publications

Statin treatment of adult human glial progenitors induces PPARγ‐mediated oligodendrocytic differentiation

Statin treatment of adult human glial progenitors induces PPARγ‐mediated oligodendrocytic differentiation

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

Consuming Functional Foods Enriched with Plant Sterol or Stanol Esters for 85 Weeks Does Not Affect Neurocognitive Functioning or Mood in Statin-Treated Hypercholesterolemic Individuals

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