sharon hope

Statin Adverse Effects FAQ: MEMORY LOSS & STATINS, AMNESIA & STATINS

To my physician,

I believe that my symptoms may be due to the adverse effects a_ssociated
with cholesterol-lowering statin drugs. I need your help to understand the
cause of my symptoms, treatment options, and the prognosis for my recovery.

Please review the references below, published medical studies that show
similar problems a_ssociated with statin drugs. These are made available
via the National Institutes of Health (NIH,
http://www.ncbi.nlm.nih.gov/Entrez/) library of biomedical journal citations
and other major repositories of medical research.

Also, I am respectfully requesting that you file an adverse effects report
with the FDA (http://www.fda.gov/medwatch/how.htm), and that you please send
a copy of the report to the to the NIH-funded Statin Study, attention: Dr.
Beatrice Golomb, Principal Investigator.
Statin Study website: http://medicine.ucsd.edu/statin/
Statin Study contact info: http://medicine.ucsd.edu/statin/contactinfo.html
UCSD STATIN STUDY E-MAIL ADDRESS: statinstudy@ucsd.edu
MAILING ADDRESS: UCSD Statin Study 9500 Gilman Dr. La Jolla, CA 92093-0995
PHONE NUMBER: (858) 558-4950

Thank you

MEMORY LOSS & STATINS, AMNESIA & STATINS

References (updated as of January 7, 2005):

Randomized trial of the effects of simvastatin on cognitive functioning in
hypercholesterolemic adults.Am J Med. 2004 Dec 1;117(11):823-9. Muldoon MF,
Ryan CM, Sereika SM, Flory JD, Manuck SB.Center for Clinical Pharmacology,
University of Pittsburgh, Pennsylvania 15260, USA. mfm10@pitt.edu"This study
provides partial support for minor decrements in cognitive functioning with
statins. Whether such effects have any long-term sequelae or occur with
other cholesterol-lowering interventions is not known." This is the second
of two studies by Muldoon, both showing measurable cognitive decline in
statin groups after only 6 months, using Neuropsychological (NP) testing.
Further, this study identifies the subset of NP tests that are "statin
sensitive" in detecting the cognitive deficits.
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15589485

Effects of lovastatin on cognitive function and psychological well-being.

Muldoon MF, Barger SD, Ryan CM, Flory JD, Lehoczky JP, Matthews KA, Manuck
SB.
After 6 months, 100% of the patients on placeboes showed a measurable
increase in cognitive function, while the statin patients showed a
measurable decrease in cognitive function in some areas.
Am J Med. 2000 May;108(7):538-46.
PMID: 10806282 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

Cognitive impairment a_ssociated with atorvastatin and simvastatin.King DS,
Wilburn AJ, Wofford MR, Harrell TK, Lindley BJ, Jones DW.Department of
Medicine, University of Mississippi Medical Center, Jackson, Mississippi
39216, USA. dking@pharmacy.umsmed.eduPharmacotherapy. 2003
Dec;23(12):1663-7. "we report two women who experienced significant
cognitive impairment temporally related to statin therapy. One woman took
atorvastatin, and the other first took atorvastatin, then was rechallenged
with simvastatin. Clinicians should be aware of cognitive impairment and
dementia as potential adverse effects a_ssociated with statin therapy."
PMID: 14695047
http://www.ncbi.nlm.nih.gov/entrez/q..._uids=14695047

"DRUGS THAT MAKE YOU FORGET"
Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the
FDA)
Volume 17, Number 3, August 1998, section 3, page 3
Simvastatn is listed under "DRUGS THAT MAKE YOU FORGET"
Recognizing the 14 reports of Amnesia under that drug, .8% of the total
adverse effects for that drug.
http://www.health.gov.au/tga/docs/pd...n/aadr9808.pdf

Statin-a_ssociated 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. Pharmacotherapy. 2003 Jul;23(7):871-80.

This study searched the MedWatch drug surveillance system of the Food and
Drug Administration (FDA) from November 1997-February 2002 for reports of
statin-a_ssociated memory loss. They also reviewed the published literature.
References from the study are good for follow-up research.

Abstract:
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

Full Study Text free on Medscape:

http://www.medscape.com/viewarticle/458867

The Role of Lipid-Lowering Drugs in Cognitive Function: A Meta-Analysis of
Observational Studies

from Pharmacotherapy
Posted 06/30/2003

Mahyar Etminan, Pharm.D., Sudeep Gill, M.D., FRCPC, Ali Samii, M.D., FRCPC

Although this study does bring the cognitive issues to light, it is a very
poor study. The authors left out the pivotal study by Dr. Muldoon, that
showed 100% of statin users had a measurable loss of cognitive ability
after 6 months, while 100% of the placebo group improved their scores.

Abstract:

http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

Full Study Text free on Medscape:

http://www.medscape.com/viewarticle/456866

Simvastatin-A_ssociated Memory Loss
Amanda Orsi, Pharm.D., Olga Sherman, Pharm.D., and Zegga Woldesela_ssie,
Pharm.D.,
Abstract: The statins are widely used to treat dyslipidemias. They are
generally a_ssociated with mild adverse effects, but rarely, more serious
reactions may occur. A 51-year-old man experienced delayed-onset,
progressive memory loss while receiving simvastatin for
hypercholesterolemia. His therapy was switched to pravastatin, and memory
loss resolved gradually over the next month, with no recurrence of the
adverse effect.
from Pharmacotherapy
Posted 06/01/2001
Page 1 of 3:
http://www.medscape.com/viewarticle/...2/7002/7001/-1
full printable version: http://www.medscape.com/viewarticle/409738_print

ADR of the Month
September 2001 Vol. 6 No. 9
EDITORS
Michelle W. McCarthy, Pharm.D.
Anne E. Hendrick, Pharm.D.

University of Virginia Health System
Department of Pharmacy Services
Drug Information Center
PO Box 800674
Charlottesville, VA 22908-0674
http://hsc.virginia.edu/pharmacy-ser...209-01htm.html


Do HMG-CoA reductase inhibitors impair memory?
The Tablet, a general member benefit published by the British Columbia
Pharmacy A_ssociation, September 2001, Volume 10 no 8.
Excerpt:
Do HMG-CoA reductase inhibitors impair memory? After taking simvastatin for
a year, a 51-year-old patient developed short term memory loss, to the
extent of being unable to complete his sentences because he would forget
what he was going to say. The drug was discontinued, replaced by
pravastatin, and within one month his memory returned.14 In a separate case,
a 67-year-old woman developed impaired short-term memory, altered mood,
social impairment, cognitive impairment and dementia after one year of
atorvastatin therapy. When atorvastatin was discontinued, her memory, mood
and cognition improved completely.15 Memory impairment in a patient
receiving atorvastatin has been reported to the BC Regional ADR Centre.
REFERENCES:
14. Orsi A, Sherman O, Woldesela_ssie Z. Simvastatin-a_ssociated memory
loss.
15. King DS, Jones DW, Wofford MR et al. First report of cognitive
impairment in an elderly patient: case report. Pharmacotherapy 2001 Mar; 21:
371.

http://www.bcpharmacy.ca/publication...et-Sep2001.pdf
See page 11 of 16:

AMNESIA & STATINS


Lipitor, Thief of Memory

Dr. Duane Graveline, retired family MD, USAF Flight Surgeon, researcher in
space medicine and US Astronaut, who suffered adverse effects from Lipitor.
The book is available through Amazon.com. Dr. Graveline maintains several
websites and is working on a second book about statin drug side effects:
www.spacedoc.net (you can start here and read about his life and his books)
http://www.spacedoc.net/lipitor_thief_of_memory.html
http://www.spacedoc.net/lipitor.htm
http://www.spacedoc.net/statin_dialogues.htm

Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the
FDA)
Volume 17, Number 3, August 1998, section 3, page 3
Simvastatn is listed under "DRUGS THAT MAKE YOU FORGET"
Recognizing the 14 reports of Amnesia under that drug, .8% of the total
adverse effects for that drug.
http://www.health.gov.au/tga/docs/pd...n/aadr9808.pdf

===========

Please see also:

Mechanistic and epidemiologic considerations in the evaluation of adverse
birth outcomes following gestational exposure to statins.Am J Med Genet.
2004 Dec 15;131A(3):287-98. Edison RJ, Muenke M.Medical Genetics Branch,
National Human Genome Research Institute, National Institutes of Health,
Department of Health and Human Services, Bethesda,Maryland 20892-3717, USA."The
cholesterol-lowering "statin" drugs are contraindicated in pregnancy, but
few data exist on their safety in human gestation. We reviewed case reports
for patterns suggesting drug-related effects on prenatal development and
considered a variety of mechanisms by which such effects, if confirmed,
might occur. This uncontrolled case series included all FDA reports of
statin exposures during gestation, as well as others from the literature and
from manufacturers. Exposures and outcomes were reviewed and were tabulated
by individual drug. Age-specific rates of exposure to each drug among women
of child-bearing age were estimated. Of 214 ascertained pregnancy exposures,
70 evaluable reports remained after excluding uninformative cases. Among 31
adverse outcomes were 22 cases with structural defects, 4 cases of
intrauterine growth restriction, and 5 cases of fetal demise. There were two
principal categories of recurrent structural defects: cerivastatin and
lovastatin were a_ssociated with four reports of severe midline CNS defects;
simvastatin, lovastatin, and atorvastatin were all a_ssociated with reports
of limb deficiencies, including two similar complex lower limb defects
reported following simvastatin exposure. There were also two cases of
VACTERL a_ssociation among the limb deficiency cases. All adverse outcomes
were reported following exposure to cerivastatin, simvastatin, lovastatin,
or atorvastatin, which are lipophilic and equilibrate between maternal and
embryonic compartments. None were reported following exposure to
pravastatin, which is minimally present in the embryo. Statins reaching the
embryo may down-regulate biosynthesis of cholesterol as well as many
important metabolic intermediates, and may have secondary effects on
sterol-dependent morphogens such as Sonic Hedgehog. The reported cases
display patterns consistent with dysfunction of cholesterol biosynthesis and
Sonic Hedgehog activity. Controlled studies are needed to investigate the
teratogenicity of individual drugs in this cla_ss."PMID: 15546153 [PubMed -
in process]


Statins and risk of polyneuropathy, A case-control study
D. Gaist, MD, PhD; U. Jeppesen, MD, PhD; M. Andersen, MD, PhD; L.A. García
Rodríguez, MD, MSc;
J. Hallas, MD, PhD; and S.H. Sindrup, MD, PhD
http://213.4.18.135/87.pdf full text

Preclinical safety evaluation of cerivastatin, a novel HMG-CoA reductase
inhibitor.
von Keutz E, Schluter G.
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract
Institute of Toxicology, PH-Product Development, Bayer AG, Wuppertal,
Germany
Am J Cardiol. 1998 Aug 27;82(4B):11J-17J.
PMID: 9737641
"In dogs, the species most sensitive to statins, cerivastatin caused
erosions and hemorrhages in the gastrointestinal tract, bleeding in the
brain stem with fibroid degeneration of vessel walls in the choroid plexus,
and lens opacity."

Subchronic toxicity of atorvastatin, a hydroxymethylglutaryl-coenzyme A
reductase inhibitor, in beagle dogs.
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract
Walsh KM, Alba_ssam MA, Clarke DE.
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann
Arbor, Michigan 48105, USA.
"The toxicity of atorvastatin (AT), an inhibitor of
hydroxymethylglutaryl-coenzyme A reductase (HMG), was evaluated in beagle
dogs. hemorrhage in gallbladder and brain, demyelination of optic nerve, and
skeletal muscle necrosis"

Finally, on memory loss and statins: Sworn testimony from the Baycol trial
in Corpus Christi, Texas. From the transcript of the AM Session on 03-05-03,
in the case Hollis Haltom Vs. Bayer Corporation. Testifying under oath,., in
response to the plaintiff's attorney's question, "What is your current
position at Bayer?", LAWRENCE POSNER, M.D of BAYER stated: "I'm the --
currently I'm the head of worldwide regulatory affairs for our prescription
drug business, which means I have responsibility in somewhere between 60 and
100 countries where we sell products for registrations, compliance, things
of that nature." Excerpts from the trial transcript follow, with the Q
indicating counsel's Question, and the A indicating Dr. Posner's Answer:
Q. So there are some concerns addressed here back in 1995 about testing up
to .8. And do you know what the nature of the concern was?
A. Yes. It was related to a side effect that occurred in the brain.
Q. Of what kind of animal?
A. It occurred in the brain of dogs.
Q. Okay. So there was a side effect that occurred in dogs, and then there
was a concern about whether you wanted to go forward and test at this higher
dose level in human beings, given what you had learned about the dogs,
right?
A. That's correct.
Q. Okay. Now, did you just say, well, let's forget about these concerns and
we'll go ahead and put .8 on the market anyway, or did you do some further
analysis that was not mentioned the other day?
A. Yes. The authors of this had -- they had two concerns. One concern was
the toxicity that they found in the brain of dogs. But the other was that
they had no way to identify this and who might be at risk before it
happened. So there was no way to detect that someone was at risk for this
side effect.
[skip some testimony on other topics]
Q. Do you remember in one kind of animal there had been some studies done
that there could be a particular kind of problem with one kind of animal?
A. Oh, yeah. Yes, from the -- that's correct, from the toxicology studies.
Q. Okay. And were you able to demonstrate to your own satisfaction, to
SmithKline's satisfaction, to the FDA's satisfaction, that that particular
problem that showed up with that kind of animal is not something that
happens in human beings?
A. Yes. We did it -- we did it by explaining the toxicology data. We also
explained it on the basis of kinetic data. That actually at the higher
levels of drug, what happens is a certain amount of drug is bound to
proteins in the body that circulate; and therefore, is not -- cannot cause
side effects. And actually, a much smaller proportion of the drug is free.
And that what you corrected for that, you actually found out that the
margins of safety were in fact greater than you would predict just from the
animal data.
Q. And as you move forward then and got approval and sold Baycol from 1997
through 2001, did that problem that had shown up with that one kind of
animal ever become a problem with human beings?
A. It was actually shown with other statins as well. It wasn't unique to
cerivastatin. It was a problem -- it was identified early on with lovastatin
and some of the others. In fact, for none of the statins did it ever predict
for any clinical problem or toxicity.
Q. So these animals would have that same problem regardless of which
statin -- or at least with other statins?
A. Certainly with lovastatin it was true.
Q. But when it came time to human beings, that just wasn't something that
happened to human beings?
A. And I think today no one pays much attention to it.

bill

I've told you 2 or 3 times that the above statement is false. The study did
not show that that 100% of statin users had a measurable loss of cognitive ability. Bill

listener

Do you really think that matters to folks like Sharonand zee? The short
answer is "no". The long answer is more complicated, of course.

I would love to hear from people who would have the audacity to print out
her "to my physician" letter and take it to their doctors and
cardiologists!

Please, anyone who does this let us know the response you get from your
doctor...(assuming he wants you to remain one of his/her patients...).

L.

sharon hope

Your comments are incorrect. In the 2000 Muldoon study, Effects of
Lovastatin on Cognitive Funciton and Psychological Well-being, the mean
changes in cognitive performance were charted in the figure. Of the five
measurements: Attention, Psychomotor Speed, Mental Flexibility, Working
Memory, and Memory Recall, the mean for the statin group was consistently
below the control group. The control group improved in all areas measured.

As for the statin group:

In 3 areas, Attention, Psychomotor Speed, and Attention, the mean was a
negative measurement: a measureable loss of cognitive ability.
In 2 areas, Attention and Psychomotor Speed, the range surrounding the mean
is not only lower than the controls, but there is no overlap - the entire
statin group's range is lower than the range for the control.

It is normal for humans to learn, and the control group shows learning. The
statin group failed to show a normal level of learning.


The 2004 Muldoon study, Randomized Trial of the Effects of Simvastatin on
Cognitive Functioning in Hypercholesterolemic Adults, summarized the 2000
study:

"In our initial investigation (7), a broad neuropsychological
assessment battery was administered, and four individual

tests showed statistically significant effects of statin

treatment: Digit Vigilance, Recurrent Words, Elithorn

Mazes, and Grooved Pegboard."

and, about the 2004 study:

"In our re-examination of the effects of statins on cognitive

functioning, we found that treatment adversely affected

performance on neuropsychological tests that were

sensitive to lovastatin in our initial investigation. Performance

on new tests was also negatively affected by simvastatin,

as compared with placebo."

and

"Tests found to be sensitive to

the effects of statins tended to have relatively large learning

or practice effects, as evidenced by the improvement

seen in placebo-treated participants. This suggests that

the effects of statins on cognition may affect patients'

abilities to benefit from prior experience or devise performance-

enhancing strategies."

sharon hope

Primary care physicians and cardiologists have responded very positively to
people with documented concerns.

The FDA and Health Canada provide for the filing of adverse affects. These
reports form the basis for studies such as the one listed,
"Statin-associated memory loss: analysis of 60 case reports and
review of the literature."

A great many articles encourage patients to write down their concerns, to
ensure that all their questions are answered. Documenting why the concern
is not unique fosters communication with the professional.

If it is your personal experience that your physician reacts negatively to a


"listener" <listener@nospam.net> wrote in message news:Xns95D9D10EBCDDFsome1outthere@38.144.126.102. ..

sharon hope

Primary care physicians and cardiologists have responded very positively to
people with documented concerns.

The FDA and Health Canada provide for the filing of adverse affects. These
reports form the basis for studies such as the one listed,
"Statin-associated memory loss: analysis of 60 case reports and
review of the literature."

A great many articles encourage patients to write down their concerns, to
ensure that all their questions are answered. Documenting why the concern
is not unique fosters communication with the professional.

If it is your personal experience that your physician reacts negatively to a


"listener" <listener@nospam.net> wrote in message news:Xns95D9D10EBCDDFsome1outthere@38.144.126.102. ..

listener

No at all. My cardiologist is a caring doctor and person. He limits the
number of patients he sees on a daily basis. When I see him he treats me
with respect, our appointments are not at all rushed, we discuss the latest
research, whats new on the internet, etc.. I trust and value his expertise
and judgements on matters cardiology. Contrary to you whom I wouldn't trust
(medically at least) past this period.

L.

listener

OK, Bill. Here are your choices at this point:

1] Reiterate your point for the 4th time.
2] Give up.
3] Concede defeat.
4] Go have a cappucino and read some Faulkner, just to relax.

L.

bill

And exactly where in either the article or your response is it shown that

"showed 100% of statin users had a measurable loss of cognitive ability
after 6 months"

The above is what you wrote.

I really think you can be blinded sometimes Sharon. The "100%" is simply not
there anywhere. I have the article. Nothing in your response supports your
assertion of 100%. Bill

sharon hope

Different readers, different interpretations.