Researchers identify clue to explain the reversible memory loss caused by statins




"What we think we've found is a laboratory demonstration of a problem in the neuron that is a more severe version for what is happening in some peoples' brains when they take statins," said Restifo, a UA professor of neuroscience, neurology and cellular and molecular medicine, and principal investigator on the project.


Restifo and Kraft cite clinical reports noting that statin users often are told by physicians that cognitive disturbances experienced while taking statins were likely due to aging or other effects. However, the UA team's research offers additional evidence that the cause for such declines in cognition is likely due to a negative response to statins.


"This is a great first step on the road toward more personalized medication and therapy," said David M. Labiner, who heads the UA department of neurology. "If we can figure out a way to identify patients who will have certain side effects, we can improve therapeutic outcomes."



Detecting, Understanding a Drugs' Side Effects


The beads indicate a sort of traffic jam, she described. In the presence of statins, neurons undergo a "dramatic change in their morphology," said Restifo, also a BIO5 Institute member.

"Those very, very dramatic and obvious swellings are inside the neurons and act like a traffic pileup that is so bad that it disrupts the function of the neurons," she said.

It was Kraft's observations that led to team's novel discovery. Restifo, Kraft and their colleagues had long been investigating mutations in genes, largely for the benefit of advancing discoveries toward the improved treatment of autism and other cognitive disorders.


Then, something serendipitous occurred: Kraft observed that one compound, then another and then two more all created the same reaction - "these bulges, which we called beads-on-a-string,'" Kraft said. "And they were the only drugs causing this effect."


"The 'beads' effect of the statins was like a bonus prize from the earlier experiment," Restifo said. "It was so striking, we couldn't ignore it."


"For some patients, just as much as statins work to save their lives, they can cause impairments," said Monica Chaung, who has been part of the team and is a UA undergraduate researcher studying molecular and cellular biology and physiology.

"It's not a one drug fits all," said Chaung, a UA junior who is also in the Honors College. "We suspect different gene mutations alter how people respond to statins."




"There is no question that these are very important and very useful drugs," Restifo said. Statins have been shown to lower cholesterol and prevent heart attacks and strokes.

But too much remains unknown about how the drugs' effects may contribute to muscular, cognitive and behavioral changes.

"We don't know the implications of the beads, but we have a number of hypotheses to test," Restifo said, adding that further studies should reveal exactly what happens when the transportation system within neurons is disrupted.


"If statins have an effect on how the nervous system matures, that could be devastating," Kraft said. "Memory loss or any sort of disruption of your memory and cognition can have quite severe effects and negative consequences."


"We have no idea who is at risk. That makes us think that we can use this genetic laboratory assay to infer which of the genes make people susceptible," Restifo said.

"This dramatic change in the morphology of the neurons is something we can now use to ask questions and experiment in the laboratory," she said. "Our contribution is to find a way to ask about genetics and what the genetic vulnerability factors are."

The Possibility for Future Research, Advice


"It's important to look into this to see if people may have some sort of predisposition to the beads effect, and that's where we want to go with this research," Kraft said. "There must be more research into what effects these drugs have other than just controlling a person's elevated cholesterol levels."


"Most physicians assume that if a patient doesn't report side effects, there are no side effects," Labiner said. "The paternalistic days of medication are hopefully behind us. They should be."

"We can treat lots of things, but the problem is if there are side effects that worsen the treatment, the patient is more likely to shy away from the medication. That's a bad outcome," he said. "There's got to be a give and take between the patient and physician."



"These are not trivial things. This could have a significant impact on your daily life, your interpersonal relationships, your ability to hold a job," Restifo said.

"This is the part of the brain that allows us to think clearly, to plan, to hold onto memories," she said. "If people are concerned that they are having this problem, patients should ask their physicians."



"There is good clinical data that every-other-day dosing give you most of the benefits, and maybe even prevents some of the accumulation of things that result in side effects," Restifo said, suggesting that physicians should try and get a better longitudinal picture on how people react while on statins.

"Statins have been around now for long enough and are widely prescribed to so many people," she said. "But increased awareness could be very helpful."


  1. Kath Bretton Kath Bretton United Kingdom says:

    Could it be possible that memory loss as a result of taking statins could be misdiagnosed as Alzheimers??

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