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Memory Loss and Statins

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When the FDA decided to mandate a black-box label on statins to warn of a possible risk of memory loss, the association between cognition and these highly prescribed class of drugs became even more important. Memory loss has only been rarely reported for statin use but it does happen. Read on to find out how much of a risk memory loss is with statin therapy and what you can do about it.

What Are Statins?

Statins are a class of related drugs that are used to reduce cholesterol levels. They act by inhibiting HMG-CoA reductase, an enzyme essential to the production of cholesterol.

The primary function of statins is, therefore, to reduce the plasma levels of LDL (low-density lipoproteins) or “bad” cholesterol by inducing LDL receptors in the liver.

By inhibiting the HMG-CoA reductase enzyme, statins

  • Block the cholesterol synthesis in the liver. Since the liver produces cholesterol at night, fast-acting statins are recommended to be taken at night
  • Increase LDL uptake from circulation by increasing the numbers of LDL receptors in the liver. These receptors then remove LDL cholesterol and turn them into harmless bile salts
  • Control inflammatory response especially in the cardiovascular system
  • Keep plaques stable and prevent the formation of thrombi (blood clots) which can block blood vessels

While the primary role of statins is the lowering of LDL levels, the secondary role is in the prevention of cardiovascular diseases.

It is estimated that statins can reduce the risks of heart attack and sudden cardiac death by as much as 60% if used in long-term therapy. The same treatment can also reduce the risk of stroke by 17%.

Even though statins are very effective for lowering LDL levels, they are less effective for increasing the levels of HDL (“good” cholesterol) and reducing triglyceride levels. This is why the major statins are combined with other agents with better activities in this regard (Niacin is combined with both Lovastatin and Simvastatin).

The best-selling drug among the statins is atorvastatin (made by Pfizer). In 2003, it became the best-selling drug ever, and later in 2012, its patent will expire.

Types of Statins

Drugs in the statin family are either synthetic or derived from fermentation. At least one of them also occurs in nature.

Sources of Statins

Synthetic Statins

Atorvastatin – popular brand name is Lipitor

Cerivastatin – popular brand name is Baycor; this statin as been withdrawn from the market due to the serious side effect of rhabdomyolysis (rapid breakdown of skeletal muscle tissue)

 Fluvastatin – popular brand name is Lescol

Pitavastatin – popular brand names are Pitava and Livalo

Rosuvastatin – popular brand name is Crestor

Statins Derived From Fermentation

Lovastatin – popular brand names are Altocor and Mevacor

Pravastatin – popular brand names are Liposat and Pravachol

Naturally Occurring Statins

Mevastatin – found in red yeast rice

Lovastatin – found in red yeast rice and oyster mushrooms

Of the statins, cerivastatin is the most effective for lowering LDL levels. Unfortunately, its serious side effects have led to its withdrawal from the market. Relative to cerivastatin, the other major statin drugs are less potent.

In decreasing potencies, these statins can be arranged in this order: rosuvastatin, atorvastatin, simvastatin, lovastatin, pravastatin, and fluvastatin.

Side Effects of Statins

Overall, statins are believed to be overprescribed. And although their side effects are rare, they are very severe when they occur.

The most common side effect of statins is muscle pain. This is caused by the progressive breakdown of the muscle, and the pain can present as ache or soreness which is strong enough to make everyday activities such as walking, uncomfortable. Rarely, this muscle breakdown progresses to full-blown rhabdomyolysis.

This musculoskeletal degeneration is even worse when statins are combined with other lipid-lowering agents such as niacin.

An increased liver enzyme is another commonly reported side effect and it can lead to hepatic dysfunction. Other side effects of statins include pancreatic dysfunction, sexual dysfunction, neuropathy, and cognitive decline.

The last two side effects demonstrate the impact of statins on the nervous system. Neuropathy affects the peripheral nervous system and involves damage to the peripheral nerves. Cognitive decline is a direct effect on the central nervous system and involves damage to neuronal pathways of the brain.

Memory loss is one of the presentations of cognitive decline.

Rarer side effects of statins include myalgia, myopathy, and a little increase in the risk of diabetes.

In February 2012, the Food and Drug Administration decided to add warnings about the risk of memory loss and diabetes to the labels of statins.

Studies on Memory Loss and Statins

Given the popularity of statins as the new treatment option for cardiovascular diseases, several studies have been done to determine both their relative efficacies and safety.

The effect of statins on memory is another well-studied aspect of these drugs. Below are the summaries of some of the most important studies.

A 2001 report published in Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy documents the appearance and progression of memory loss in a 51-year old man placed on simvastatin to treat high cholesterol levels.

The pattern of memory loss was described as delayed-onset which means that it started only after taking the statin drug for a while. Once started, however, the memory loss progressed steadily.

To reverse the memory loss, the patient’s doctor switched him to another statin, pravastatin.

With pravastatin, the memory loss resolved steadily over a period of 1 month, and the new statin did not cause another delayed-onset memory loss.

In another report published in the same journal in 2003, two women placed on statins were reported to show definitive signs of cognitive impairment including memory loss. While one woman took atorvastatin, the other took atorvastatin and then simvastatin.

A third report published in the same journal appeared in 2006. In this one, the first reported case of memory loss due to one of the new statins, rosuvastatin, was reported. It was experienced by a 56-year old man who was taking 10 mg/day of the new statin to lower his cholesterol levels.

This short-term memory loss gradually resolved after the drug was withdrawn.

This same journal published a 2003 paper that reviewed all 60 case reports of statin-related memory loss available until then. Of these 60 reports, 36 involved simvastatin, 23 involved atorvastatin, and 1 involved pravastatin.

In half of these cases, the onset of memory loss was reported within the first 2 months of starting the statin. Also, 56% of patients experienced a reversion of memory loss when the statin was withdrawn. Resuming statin use usually causes the recurrence of memory loss.

It is worth noting that other studies show that statins actually improve cognitive function and others show that there is no net effect on cognition.

The case for memory loss is also not universal. Critics argue that the studies that link memory loss to statins are mostly observational and not large, randomized, placebo-controlled studies. These critics also argue that people who experience memory loss following statin use are likely more prone to cognitive impairment in the first place.

However, the evidence for statin-caused memory loss is significant enough for the FDA to demand that manufacturers place warnings on the labels of statin drugs.

How To Relieve Memory Loss Caused By Statins

The exact mechanism by which statins may cause memory loss remains unknown. Most of the theories regarding how this might occur have also been disproven.

The most promising theory linking statins to brain function does not actually support the observation that statin-caused memory loss. This theory involves the relationship between cholesterol and amyloid synthesis.

Increased cholesterol intake has been associated with increased amyloid synthesis.

Amyloids are complex proteins that structurally resemble starch. When they collect in the brain, they can cause cognitive decline. Amyloid proteins have been implicated in the appearance and progression of Alzheimer’s disease.

Therefore, statins should reduce amyloid synthesis which should reduce the risk of dementia and improve cognitive function.

Unfortunately, this theory has received no support from observational studies. Clinical evidence obtained from actual cases all point to the fact that statins can cause memory loss more often than they can reduce cognitive dysfunction.

Discussed below are some ways to relieve the memory loss caused by statins.

However, make sure to consult your physician before making changes to your statin therapy. Even the FDA agrees that memory loss is a rare side effect of statins. Therefore, a medical professional who can properly determine the risk-reward potential of statin therapy can provide a better assessment of the direction further treatment needs to take.

Stop Statin Therapy

Most observational studies show that after stopping statins the memory loss experienced gradually improves and no permanent damage is done. To know for certain whether the statin drug you are taking is the cause of memory loss, stop the drug for at least 10 days, and see if there is any improvement in memory consolidation and recollection.

If your memory improves then you should consult your doctor for alternatives. If the memory loss continues, it is most likely not caused by statin.

Lower the Dose of Statin

Sometimes, the side effects of statins are relieved simply by reducing the doses of the drugs given. This is true of the muscle pain caused by statins. However, lowering the dose can also reduce the efficacy of the statin and lead to poor control of cholesterol levels.

Change to Another Statin Drug

Observational studies seem to indicate the not all statins cause memory loss. The most likely statins to cause memory losses are atorvastatin and simvastatin.

However, most experts believe that all statins have the potential of causing memory loss. Since each patient responds differently to drugs, it is possible that other statins besides the two named above may not cause memory loss in some users.

Change to Another Cholesterol-lowering Drug

Where statins are known to definitely cause memory loss, doctors sometimes recommend other cholesterol-lowering drugs.

A prime alternative to statins is the drug, Ezetimibe (commonly known as Zetia). However, it is not as effective as statins.

A combination of simvastatin and ezetimibe is known under the brand name Vytorin can also be of help. Since it includes a lower dose of simvastatin, the drug may reduce side effects such as memory loss while keeping up the cholesterol-lowering efficacy of statins.

Avoid Drug Combinations that Act on the Brain

Centrally active drugs such as antidepressants, sedatives, anxiolytics, and even opioid painkillers are known to cause side effects. When these drugs are combined with statins, the likelihood of memory loss is magnified.

Therefore, to reduce the risk of memory loss, statins should not be combined with drugs that act on the central nervous system.





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