Statins rank among the most commonly prescribed drugs in the United States. The number of individuals who reported using statins, which help reduce blood cholesterol levels, surged from 31 million in 2008 to 92 million in 2019. However, recent studies echo earlier findings that highlight some users of statins experience short-term memory loss and cognitive impairment.

While it's true that cholesterol levels are linked to cardiovascular risk, it's important to note that cholesterol plays several essential roles in our bodies, including aiding nerve function. The brain, being the organ with the highest cholesterol content, can be notably affected when cholesterol levels are reduced through the use of statins.

What are nerves made of?

Maintaining the health of our nerves is crucial, and they are encased in a myelin sheath. You can compare this to the insulation wrapped around an electrical wire. This sheath is vital not only for safeguarding the nerves but also for effectively transmitting electrical signals. In our bodies, specific cells known as oligodendrocytes are responsible for forming this protective layer through a process termed myelination.

Without it, a signal can't be transmitted, rendering the nerve nonfunctional. The sheath primarily consists of fats (lipids) and its creation necessitates significant fatty acid and lipid production. Besides nerve cells, lipids play a major role in cholesterol transport within our bloodstream. Cholesterol can't freely float in our arteries, so it gets transported throughout the body on lipoproteins (a blend of lipids and proteins). You might recognize some of them, such as LDL (low-density lipoprotein or “bad” cholesterol) or HDL (high-density lipoprotein or “good” cholesterol).

Statins reduce cholesterol and harmful lipoproteins, resulting in a decrease in your LDL levels. However, this medication may also lower other essential lipids. According to one study, statins reduce levels of specialized lipids known as sphingomyelin, which are necessary for creating nerve cells. This reduction might be problematic since sphingomyelin appears to offer protection against neurodegenerative conditions like Alzheimer’s disease, with higher levels being associated with slower cognitive decline.

Fatty acids are essential for initiating the formation of these unique fats, and fortunately, nerve cells can produce their own. This capability appears to explain why statins might affect the brain. While the liver is responsible for creating cholesterol and distributing it throughout the body, the brain can synthesize cholesterol within its own cells. This is because lipoproteins cannot penetrate the blood-brain barrier, a protective layer that keeps most substances in our blood from entering the brain's circulation. However, some statins have the ability to cross this barrier and exert effects directly on the brain.

Good and bad for the brain?

In the initial trials of statins, researchers noticed a link between higher doses and minor side effects such as restlessness and mental confusion. However, subsequent studies did not find this connection significant enough to be classified as a side effect. A review conducted in 2003 of 60 case reports revealed a notable correlation between cognitive problems and these drugs.

Two studies conducted by Dr. Matthew Muldoon, a cardiologist at the University of Pittsburgh, confirmed these results. His research demonstrated that lovastatin led to reductions in memory and attention. Furthermore, in a subsequent double-blind, randomized trial, participants taking statins exhibited a notably poorer learning outcome compared to those on a placebo.

In 2012, the FDA made a label change after multiple studies raised similar concerns, alerting doctors and patients about the cognitive side effects associated with statins. However, since voluntary reporting only accounts for 1–10% of actual events, the true number of affected cases is significantly higher than what's reported.

The 2012 statement clearly indicated that the “FDA continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.” This was supported by the American College of Cardiology and the American Heart Association, who, upon reviewing randomized control trials, did not find proof of negative cognitive effects or a heightened risk of dementia. Although the evidence varies in strength, it is evident that some users of statins do experience adverse cognitive effects.

Why some people are affected

Atorvastatin and simvastatin are the most widely used statin medications, accounting for about 70% of all statin prescriptions. In 2018, atorvastatin was the second most commonly prescribed drug in the United States. Researchers observed a higher incidence of cognitive adverse events with these medications, likely due to their lipophilic nature, or affinity for fats. Since nerve cells are composed of fatty acids and lipids, and the human brain is 60% fat, it stands to reason that these fat-loving statins are more capable of crossing the blood-brain barrier.

Statin drugs that are more hydrophilic, or water-loving, typically have more difficulty achieving this. The hypothesis is that a local reduction in cholesterol levels in the brain can hinder the synthesis of the myelin sheath, consequently impairing cognitive function.

Other elements such as race/ethnicity, gender, and genetic markers might also have considerable influence. Beyond their cholesterol-lowering effects, statins can enhance blood vessel function, decrease vascular inflammation, and potentially lower the risk of dementia. However, the most extensive study conducted so far on the long-term use of statins for Alzheimer’s and cerebrovascular disease in older individuals found no significant advantages.

It’s complicated

As with many medications, people react differently. Some find them helpful, while others do not. The silver lining is that you can discontinue a medication if its drawbacks overshadow the benefits. However, in most cases, the positives of using statins significantly outweigh the negatives. If you suspect you're experiencing negative cognitive effects from a statin, these issues should subside once you stop taking it, but you may need to switch to another statin. Always consult with your doctor or prescriber before stopping any medication. You wouldn't want to give them a heart attack.