The side effects of statins: Heart healthy and head harmful?

February 12, 2008        Michael O'Riordan

New York, NY - The cognitive side effects, especially memory loss,
associated with statins resurfaced again this week with an article in
the February 12, 2008 issue of the Wall Street Journal, in which some
doctors voiced concerns that the cholesterol-lowering medications,
specifically atorvastatin (Lipitor, Pfizer), might be helping patients'
hearts but actually putting their memory in jeopardy [1]. To date,
evidence for this effect is only anecdotal.

In the article, Dr Orli Etingin, vice chair of medicine at New York
Presbyterian Hospital, is quoted as saying that atorvastatin, the
best-selling drug on the market, "makes women stupid." Etingin told the
Journal that 24 of her female patients taking atorvastatin lost the
ability to concentrate or recall words. While tests showed nothing
irregular, the women regained full cognitive capacity when the statin
was stopped, and some women did better on other statins.

The examples cited by Etingin, founder and director of the Iris Cantor
Women's Health Center (New York), are anecdotal, but she said more
studies are needed to assess the cognitive effects of statins,
especially in women.

These concerns, despite their observational nature, are not new and have
surfaced in medical journals and meetings, as well as the mainstream
media, for a number of years. As the Journal notes, "Lowering
cholesterol could slow the connections that facilitate thought and
memory. Statins may also lead to the formation of abnormal proteins seen
in the brains of Alzheimer's patients."

The evidence, however, linking statin use to declines in cognitive
function or to the development of diseases such as amyotrophic lateral
sclerosis (ALS), also known as Lou Gehrig's disease, as well as to the
possible protection from Alzheimer's and Parkinson's, are scattershot at
best. In the Journal, reporter Melinda Beck notes that Pfizer, the maker
of atorvastatin, states the drug has been tested in 400 clinical trials,
with no evidence establishing a causal link between atorvastatin and
memory loss. Cardiologist Dr Antonio Gotto (Weill-Cornell Medical
School, NY) believes the benefits of the drugs outweigh the risks,
telling Beck that he "would hate to see people frightened off taking
statins because they think it's going to cause memory loss."

Dr Michael Miller (University of Maryland Medical School, Baltimore)
commented to heartwire that he has heard anecdotal reports of cognitive
declines with statin use but pointed to a recently published paper in
Neurology, with lead investigator Dr Zoe Arvanitakis (Rush University
Medical Center, Chicago, IL), showing that in nearly 1000 patients the
use of statins was not related to incident Alzheimer disease, changes in
cognition, or continuous measures of Alzheimer's pathology or infarction
[2]. Numerous other articles, many covered by heartwire, show
conflicting data supporting and not supporting a link between statin use
and cognitive decline.

Speaking with heartwire, Arvanitakis said that her study involved both
men and women and the results do not contradict the observational
findings but simply do not support the anecdotal evidence seen in
clinical practice.

"There is a lot of interest right now with respect to statins and
cognitive decline and Alzheimer's, so we need to be aware of the
anecdotal evidence," she said. "There are some people who do believe
that statins have a negative effect on cognitive function, and others
who believe it has a beneficial or protective effect, but right now we
just don't know. . . . The bottom line is that the evidence is mixed."

Asked about the cognitive side effects, Dr Roger Blumenthal (Johns
Hopkins University Medical Center, Baltimore) told heartwire he has had
some patients "who think that they are not as sharp mentally on statins,
but the numerator is very small and the denominator is very large." If
there is a good reason to treat a patient with a statin, he'll try
another drug or every-other-day dosing, but he noted that he does not
need to do this frequently, as 90% or more patients "have no problems
with statins."

Still, anecdotally, "the chronology can be very telling," Dr Gayatri
Devi (New York University School of Medicine) told the Journal. She has
treated six patients with memory loss traceable to statin use, with the
changes occurring within six weeks of starting the cholesterol-lowering
drug. "It's a handful of patients, but for them, it made a huge difference."

While cognitive declines occur in men, too, women are affected
particularly harder because they are losing estrogen in menopause,
something that can also cause changes in cognitive function, writes
Beck. She quotes Women's Heart Program director Dr Nieca Goldberg (New
York University School of Medicine) who prescribes statins only to women
with elevated LDL cholesterol and who have already had an MI. For
others, including those with high LDL cholesterol but no risk factors,
Goldberg recommends dietary changes and exercise.

With the evidence all over the map and with observational reports not
going away, studies are being conducted to examine the effects of
statins on "thinking, mood, behavior, and quality of life," writes the
Journal. The researchers, led by Dr Beatrice Golomb (University of
California, San Diego), are collecting anecdotal experiences of patients
on statins. Muscle aches are the most commonly reported side effect,
thus far, with memory problems the second most common side effect, in
approximately 5000 reports to date.

       
Sources

   1. Beck M. Can a drug that helps hearts be harmful to the brain?
Wall Street Journal, February 12, 2008. Available at:
http://online.wsj.com/public/us.
   2. Arvanitakis Z, Schneider JA, Wilson RS, et al. Statins, incident
Alzheimer disease, change in cognitive function, and neuropathology.
Neurology 2008; DOI:10.1212/01.wnl.0000288181.00826.63. Available at:
http://www.neurology.org.

       
Related links

      Statins offer no protection against Alzheimer's disease
      [HeartWire > Medscape Medical News; Jan 16, 2008]

      Link between statins and cognition gets more complicated
      [HeartWire > Medscape Medical News; Nov 15, 2007]

      Simvastatin linked to reduced incidence of dementia, Parkinson's
disease
      [HeartWire > Medscape Medical News; Jul 20, 2007]

      WSJ reports on possible interaction between statin use and
development of ALS
      [HeartWire > MediaPulse; Jul 04, 2007]

      Low LDL, statin use, and Parkinson's disease: Another benefit for
statins or potential harm?
      [HeartWire > News; Jan 18, 2007]

      Low cholesterol linked to reduced cognitive function
      [HeartWire > News; Mar 23, 2005]