When heart drugs cloud the brain

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This month I have an article in Scientific American MIND about the controversial link between statin drugs and memory loss. Hundreds of statins users have registered cognitive complaints with Medwatch, the FDA’s adverse drug reaction database. But drug companies don’t yet recognize memory loss as a side effect, and to be fair, at first consideration, it seems like a strange association—why in the world would a heart medication affect your brain?

Dig a little deeper, though, and it makes a lot of sense. A study published in the Archives of Neurology in 2002 reported that after taking high-doses (80mg) of the statin Zocor for 24 weeks, subjects had half as much circulating brain-derived cholesterol as they did before they started taking the drugs. A good 70 percent of the brain is comprised of cholesterol; it makes up the myelin sheaths that surround nerves, allowing them to transmit electrical impulses quickly. It is also required for the production of new synapses, or connections between neurons, an as a result is likely to play a crucial role in memory formation and brain plasticity.

But statins could also affect memory for reasons that have little to do with cholesterol. Statins block an early step along a biochemical pathway called the mevalonate pathway, which controls the production of many compounds, not just cholesterol. According to Beatrice Golomb, an associate professor of medicine at the University of California, San Diego, statins inhibit the production of Co-enzyme Q10, an antioxidant that plays an important role in the mitochondria, the cellular organelles responsible for energy production. Co-enzyme Q10 mops up damage-causing free radicals produced during energy-production processes, so when there’s less of it circulating as a result of statin use, more free radicals are around to cause mitochondrial DNA damage. This damage could ultimately impair and kill cells throughout the body, Golomb says—especially brain and muscle cells, which have extremely high energy requirements.

Golomb’s theory may also explain why only a subset of people seem to suffer from statin-related side-effects. When Georgirene Vladutiu, a professor of pediatrics, neurology and pathology at the State University of New York at Buffalo, analyzed blood samples from people suffering from statin-related muscle pain (a recognized statin side-effect) in 2006, she discovered that they were more likely to have genetic defects related to mitochondrial function than statin users who did not complain of muscle pain. In other words, the people who may suffer the most from statin side-effects may be people who have a genetic predisposition to mitochondrial problems.

I’m curious to know if any of you have experienced cognitive problems on statins and, if so, what you have done about it. If you have told your doctors, how have they reacted?  In 2007, Golomb and her colleagues interviewed 87 statin users who had talked to their physicians about their cognitive side-effects and found that more than half of the doctors had dismissed the possibility outright. I’m wondering if this is still happening, or if doctors are coming around to the possibility that statins might elicit real memory problems. These may not be common side-effects, but their being rare does not make them any less real.

Citations:

Locatelli S, Lütjohann D, Schmidt HH, Otto C, Beisiegel U, & von Bergmann K (2002). Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain. Archives of neurology, 59 (2), 213-6 PMID: 11843691

Barres BA, & Smith SJ (2001). Neurobiology. Cholesterol–making or breaking the synapse. Science (New York, N.Y.), 294 (5545), 1296-7 PMID: 11701918

Buhaescu I, & Izzedine H (2007). Mevalonate pathway: a review of clinical and therapeutical implications. Clinical biochemistry, 40 (9-10), 575-84 PMID: 17467679

Golomb BA, & Evans MA (2008). Statin adverse effects : a review of the literature and evidence for a mitochondrial mechanism. American journal of cardiovascular drugs : drugs, devices, and other interventions, 8 (6), 373-418 PMID: 19159124

Vladutiu GD, Simmons Z, Isackson PJ, Tarnopolsky M, Peltier WL, Barboi AC, Sripathi N, Wortmann RL, & Phillips PS (2006). Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle & nerve, 34 (2), 153-62 PMID: 16671104

Golomb BA, McGraw JJ, Evans MA, & Dimsdale JE (2007). Physician response to patient reports of adverse drug effects: implications for patient-targeted adverse effect surveillance. Drug safety : an international journal of medical toxicology and drug experience, 30 (8), 669-75 PMID: 17696579

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