Re: Lipitor users experience Amnesia 38,461% more frequently than the normal population



Bill wrote:
> "Sharon Hope" <shope@xxxxxxxx> wrote in message
> news:rsudnZbZct08m37fRVn-jg@xxxxxxxxxxxxxx
> > http://www.medscape.com/viewarticle/458867_4
> >
>
> The following is from tables in the study (which I hope transmit OK - if not
> you will need to look up the study.)
>
> Tables
> Table 1. Published Prospective, Randomized, Controlled Studies of Effects of
> Statins or Diet on Cognition
>
>
> Treatment No. of Patients Age Range
> (yrs) Results
> Simvastatin[9] 20,536 40-80 No statistically significant difference in
> cognition between statin and placebo groups.
> Pravastatin[10] 2891 (pravastatin)
> 2913 (placebo) 70-82 No statistically significant effects on MMSE,
> word recall, or performance time.
> Lovastatin[11] 98 (lovastatin)
> 96 (placebo) 24-60 Placebo group improved from baseline on all
> neuropsychological tests (p<0.04); lovastatin group improved from baseline
> only on memory recall test (p=0.03).
> Simvastatin, pravastatin[12]
> (crossover study) 36 40-60 No statistically significant effects on
> word recall test, profile of mood states, choice reaction time test, symbol
> substitution, or drowsiness rating.
> Simvastatin, pravastatin[13]
> (crossover study) 25 20-31 No statistically significant effects on EEG
> potential, mood, sleep, or cognitive performance.
> Simvastatin[14] 24 (simvastatin)
> 20 (placebo) 59-77 No statistically significant effects on CSF levels,
> AB40, or AB42.
> Low-fat diet, low-cholesterol diet[15] 52 (low-fat diet)
> 53 (low-cholesterol diet)
> 50 (control) 41-65 At 12 wks, results of the sustained attention task
> differed significantly (p<0.001) in groups with reduced cholesterol.
>
> MMSE = Mini-Mental State Examination; EEG = electroencephalogram; CSF
> = cerebrospinal fluid.
>
>
>
> Table 2. Observational Studies of Effects of Statins on Cognition
>
>
> Design Statins Prescribed Treatment Group,
> No. of Patients Age (yrs) Results
> Epidemiologic, retrospective nested case-control study[2]
> Atorvastatin, cerivastatin, fluvastatin, pravastatin, simvastatin Group 1:
> Dementia, 284, Statins, 13
>
> Group 2: Controls, 1080, Statins, 104 >/= 50 Relative risk of dementia
> was reduced 0.29 in patients taking statins (95% CI 0.13-0.63, p=0.002).
> Retrospective, multicenter, epidemiologic, cross-sectional analysis[3]
> Lovastatin, pravastatin, simvastatin Lovastatin, 4180
> Pravastatin, 2326
> Simvastatin, 3580 >/= 60 Prevalence of AD was 60-73% lower in patients
> receiving lovastatin or pravastatin than in the entire cohort (p<0.001).
> Retrospective cohort case-control study[4] Not specified Statins, 57
> Controls, 2248 >/= 65 Statins were associated with a lower risk of
> dementia in patients aged < 80 years (OR 0.26, 95% CI 0.08-0.88).
> Multicenter secondary analysis[5] Simvastatin, atorvastatin,
> pravastatin, lovastatin, fluvastatin Statins, 583
> Controls, 454 < 80 Modified MMSE scores were higher in the statin
> group (93.7) vs the control group (92.7) (p=0.02).
> Retrospective study of postmenopausal women[6] Not specified Statins,
> 113
> Controls, 542 52-98 Prevalence of dementia-AD was decreased (p<0.05)
> and MMSE scores were higher in the statin vs the control group (p=0.025).
>
> CI = confidence interval; AD = Alzheimer's disease; MMSE = Mini-Mental
> State Examination.
>
>
>
> Table 3. Comparison of Prescribing Information
>
>
> Statin Recommended
> Dosage
> (mg/day) Frequency of
> Cognitive-Related
> Adverse Events
> Atorvastatin[23] 10-80 < 2% (amnesia)
> Pravastatin[21] 10-80 < 1% (memory impairment)
> Simvastatin[22] 5-80 Not specified
>
>
>
> Table 4. Potential Mechanisms by Which Statins May Affect Brain Function
>
>
> Effect Mechanism
> Platelet activity platelet aggregation and deposition onto damaged
> vessel walls
> Thrombin generation thrombus generation
> generation of thrombin cleavage peptides
> Nitric oxide formation cerebral blood flow
> toxic production of nitric oxide
> Antiinflammatory effects -amyloid peptides A42 and A40
> formation of proinflammatory isoprenoids
> expression of adhesion molecules
> elaboration of potentially damaging cytokines from macrophages during
> cerebral ischemia
> Antioxidant effects free radical injury and lipoprotein oxidation
> Inhibition of cholesterol synthesis Can be good or bad. May interfere
> with neuronal function if statin is lipophilic; cholesterol essential for
> membrane integrity.
>
>
>
> > http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=12885101&dopt=Abstract
>
> I think it is important to state what this says:
>
> "Statin-associated memory loss: analysis of 60 case reports and review of the
> literature.
>
> Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM.
>
> Drug Information Service, Duke University Medical Center, Durham, North
> Carolina 27710, USA.
>
> OBJECTIVE: To review case reports of statin-associated memory loss as well as
> the available published evidence for and against such a link. METHODS: We
> searched the MedWatch drug surveillance system of the Food and Drug
> Administration (FDA) from November 1997-February 2002 for reports of
> statin-associated memory loss. We also reviewed the published literature
> (using MEDLINE) and prescribing information for these drugs. RESULTS: Of the
> 60 patients identified who had memory loss associated with statins, 36
> received simvastatin, 23 atorvastatin, and 1 pravastatin. About 50% of the
> patients noted cognitive adverse effects within 2 months of therapy. Fourteen
> (56%) of 25 patients noted improvement when the statin was discontinued.
> Memory loss recurred in four patients who were rechallenged with the drug.
> None of the 60 reported cognitive test results. Two placebo-controlled trials
> found no benefits for statins on cognition or disability. One randomized
> controlled trial of simvastatin found no effects on cerebrospinal amyloid
> levels. In one small, randomized study, patients receiving statins showed a
> trend toward lower cognitive performance than those receiving placebo. Five
> observational studies found a lower risk of dementia among patients receiving
> statins. CONCLUSION: Current literature is conflicting with regard to the
> effects of statins on memory loss. Experimental studies support links between
> cholesterol intake and amyloid synthesis; observational studies indicate that
> patients receiving statins have a reduced risk of dementia. However, available
> prospective studies show no cognitive or antiamyloid benefits for any statin.
> In addition, case reports raise the possibility that statins, in rare cases,
> may be associated with cognitive impairment, though causality is not certain.
>
> Publication Types:
> a.. Review
> b.. Review, Multicase
> c.. Review, Tutorial
>
> PMID: 12885101 [PubMed - indexed for MEDLINE] "
>
> Note the "rare" and "causality is not certain" in the final sentance. They
> found 60 people after reviewing all the literature.
>
> Bill



COMMENT:

That's the best summary I've ever seen. Where's it from, again? I
don't have the medscape account so I can't see the reference.

In any case, it should spike the guns completely until Golomb comes out
with her numbers. Current experience from other trials (summarized
above) simply DOES NOT show that statins are big causers of mental side
effects.

SBH

.

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