Wonder drug that stole my memory

Statins have been hailed as a miracle cure for cholesterol, but little is known about their side effects.

I had just walked in to the party, and spotted a familiar face. "Oh, hi," I said brightly, "you're just the person I wanted to see: I had something to ask you." There was a pause. "Yes?" said my friend gently. I stood there in confusion. I couldn't remember her name. And the thing I wanted to ask her had slipped completely out of my mind.

That was a year ago, and it had been happening to me more and more frequently. At first I could shrug it off as examples of those senior moments we all have in late middle age. It started with the names of people and places. "Oh, you know, that man who wrote a book about depression. He used to live in that road just off Primrose Hill. Begins with G."

I have always been a trifle absent-minded. Walking home from prep school, I was usually the one who left his lunchbox behind, or managed to lose his cap while taking a short cut through the copse. Even now, I am not the most reliable person in the world with whom to leave the back door keys. But this was different. I was beginning to be plagued not just with forgetfulness but with confusion. I got into small panics, when for a moment I couldn't make sense of what was going on around me or what I was supposed to be doing. Playing doubles tennis, for example, as I do most weekends, I would get the score wrong and I had to watch the other three like a hawk when we started each new game, so that I knew to stand in the right place.

Worse still was when not only proper nouns but also everyday words escaped me. As a novelist and journalist, my whole life is about words: getting them right and putting them down on the page speedily. Now I found myself looking perplexedly at the keyboard, not only for the right word, with the help of a thesaurus, but where to find the letters I wanted on the laptop.

My wife was by now accustomed to providing names and finishing my sentences for me. It was an unhappy time for both of us. She thought that this was how life was going to be for the next 30 years; I became unusually reclusive for fear of making a fool of myself in public. Both of us read about Alzheimer's with a gripping sensation around the heart, although my symptoms did not seem to fit the classic patterns of the condition.

What, if anything, did seem to fit the pattern, besides incipient dementia? I was pretty healthy, except for moderately high cholesterol, for which I took the statin drug Simvastatin. Other than that I went through periods of taking vitamin supplements – that was all.

"Did you say Simvastatin?" asked a friend. "Did you know that statins have been linked to memory loss?"

This was news to me. Statins are, I think, among the greatest successes of modern pharmacology. They work by blocking the action of a chemical in the liver which is needed to make cholesterol. By lowering blood-cholesterol levels, they help defend against arterial diseases such as high blood pressure, diabetes and strokes.

My doctor, when prescribing me tablets of Simvastatin to be taken once a day, described it to me, rightly I'm sure, as a "wonder drug" which deserves to be taken by most of the Western world.

Because the drug worked so well in reducing my cholesterol, it never occurred to me to think of statins as a feature in my memory loss. But looking back to when I began taking that 40-milligram dose, I realised that it more or less coincided with the intensification of my memory problems. I decided to take the bull by the horns. I went to our very good local doctor, told her what was happening, and asked for her advice. She nodded, and said: "We'll take you off statins for three months. Let's see what happens".

For six weeks or so, I noticed. I continued to go around in a daze. Then my life began changing back. At dinner parties I could tell stories without losing track halfway through. In tennis, I didn't have to think about the scores or where I stood at changeovers. Words came back like old friends jostling to greet me. My shattered confidence began returning as decisions became easier to make. The other day, my wife said, "I feel I've got my husband back".

The strangest thing was that for most of last year I noticed something I had never suffered from before: poor circulation in my fingers and toes. I thought my numb white index fingers might be connected to my furious two-finger typing. Nearly every day I had to stop and massage my fingers to get the blood circulating. Then, at about the time my memory began returning, my circulation came back to normal too. Through this coldest winter for 20 years, my fingers have not once lost their nice healthy pink.

I would be a fool to pretend that I know anything about the circulation of the blood to the brain, but an even greater fool to suppose that the medication I took might not somehow be connected to it. Unscientific and simplistic though it is, I truly believe what the history of my symptoms suggests that the Simvastatin I took, so effective in lowering my cholesterol, simultaneously affected my brain.

I am not alone in coming to this conclusion. Google "statins" and "memory loss" and you will come upon a selection of websites connecting the two. In a recent Dutch survey of 4,738 statin users, a quarter reported physical or mental side effects, of whom 13 per cent reported memory loss.

Nobody knows why this should be, although many researchers point out that statins can block the production of Co-Q10, a vital heart nutrient. The Canadians now print a mandatory warning on all packets of statins that Co-Q10 reduction "could lead to impaired cardiac function".

The Medicines and Healthcare products Regulatory Agency and the Commission on Human Medicines include memory loss as one of the potential adverse effects of taking statins. A recent discussion paper on statins and memory loss, published by the Pharmacotherapy Press, reports that "the effects of these agents on the human brain are not [as] well established. The more lipid-soluble the statin, the greater propensity it has to cross the blood-brain barrier and affect the central nervous system. According to some reports, Simvastatin is the most lipophilic drug in its class."

Sounds worrying to me. Last month Britain's "heart tsar", Professor Roger Boyle, argued that millions of healthy people over 40 should be considered for statin therapy after a study published in the Archives of Internal Medicine suggested the drugs were even more effective than previously thought. The study, of 230,000 people, found that the drugs halved the risk of heart attacks. At present, the prescription of statins for primary prevention of heart disease is confined to those considered to be at high risk of developing heart disease.

Maybe they are right and the benefits of these drugs outweigh the side-effects. However, now that I've got some of my memory back, I'll remember to look for other ways of keeping down my cholesterol.

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Taking statins won't extend your lifespan -- and may reduce it

In an inconvenient letter to the Editor of the New England Journal of Medicine, Joel M. Kauffman, Ph. D. (University of the Sciences in Philadelphia, Philadelphia, PA 19104) pointed out that although statins do lower serum cholesterol, their side-effects may more than cancel out any benefit. The letter was not published

The review by Hiatt (May 24 NEJM)1 on the preferred treatment of peripheral arterial disease and claudication contains some apparent misunderstandings. Since cholesterol levels as low as 100 mg/dL are strongly associated with higher cancer rates, and high cholesterol levels, although correlated with atherosclerosis since 1913, have not been proven to cause it,2 Hiatt's recommendation to strive for very low cholesterol levels is misdirected.

While statin drugs certainly lower cholesterol levels, a surrogate endpoint, three of the studies did not lower total mortality significantly, a hard endpoint, and earlier cholesterol drugs, such as cholestyramine and colestipol, and even early trials of lovastatin showed higher death rates; moreover, some statin drugs increased breast cancer rates in women.3

In reviewing the use of aspirin, Hiatt seems unaware that the Physicians Health Study used aspirin containing calcium and magnesium, and that overall death rates were almost the same as for placebo. Where plain aspirin was used in another equally well-controlled trial the overall death rate was slightly higher than for the subjects on placebo.4

Hiatt dismissed the utility of EDTA-chelation treatments (his ref. 116); but a different review has solid evidence of the effectiveness of chelation in 87% of patients (r = 0.88), and an explanation for a number of the trials that showed little effect.5

Because of its misunderstandings and omissions, this review cannot be considered authoritative.

References:

1. Hiatt, W. R. Medical Treatment of Peripheral Arterial Disease and Claudication. N Engl J Med 2001:344:1608-20.

2. Stehbens, W. E. Coronary Heart Disease, Hypercholesteremia, and Atherosclerosis I. False Premises and II. Misrepresented Data. Experimental and Molecular Pathology 2001:70:103-119, and 120-139.

3. Ravnskov, U. The Cholesterol Myths: Exposing the Fallacy that Saturated Fat and Cholesterol Cause Heart Disease, New Trends Publishing, Washington, DC, 2000.

4. Kauffman, J. M. Should You Take Aspirin to Prevent Heart Attack? J Sci Exploration 2000:14:623-41.

5. Chappell, L. T., Janson, M. EDTA Chelation Therapy in the Treatment of Vascular Disease. J Cardiovasc Nurs 1996:10:78-86.

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