Can statins (HMG-CoA reductase inhibitors) cause memory changes?

From the Guidelines

Statin use is not supported by evidence to cause cognitive dysfunction or dementia, and therefore, should not be a concern for individuals with diabetes at high risk for cardiovascular disease. The most recent and highest quality study, published in 2022 1, found that data do not reveal an adverse effect of statins on cognition. This study, along with others 1, consistently shows that statins do not have a significant impact on cognitive function.

Key Points

• Several large randomized trials of statin versus placebo have shown no differences in cognitive tests between statin and placebo 1.
• The addition of ezetimibe or PCSK9 inhibitors to statin therapy has not been associated with changes in cognitive function 1.
• The U.S. Food and Drug Administration's postmarketing surveillance databases have revealed a low reporting rate for cognitive-related adverse events with statin therapy, similar to rates seen with other commonly prescribed cardiovascular medications 1.
• The cardiovascular benefits of statins significantly outweigh the small risk of cognitive side effects, which are typically mild and reversible 1.

Recommendation

Statin therapy should not be withheld from individuals with diabetes at high risk for cardiovascular disease due to concerns about cognitive decline. If memory problems occur while taking statins, patients should consult their healthcare provider, who may recommend switching to a different statin, adjusting the dosage, or trying a non-statin cholesterol medication 1.

From the FDA Drug Label

There have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with the use of all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks)

Statin use has been associated with rare reports of cognitive impairment, including memory loss and memory impairment. These reports are generally nonserious and reversible upon statin discontinuation. The time to symptom onset and resolution can vary, but the median time to symptom resolution is 3 weeks 2 3.

• Key points:
  • Rare reports of cognitive impairment associated with statin use
  • Includes memory loss and memory impairment
  • Generally nonserious and reversible upon statin discontinuation
  • Variable times to symptom onset and resolution, with a median of 3 weeks to symptom resolution

From the Research

Statin-Associated Memory Changes

• Statins, also known as HMG-CoA reductase inhibitors, have been reported to cause memory changes in some individuals, although the evidence is conflicting 4, 5, 6, 7, 8.
• A study published in 2003 found that 60 case reports of statin-associated memory loss were identified, with 36 patients receiving simvastatin, 23 atorvastatin, and 1 pravastatin 4.
• Another study published in 2024 found that atorvastatin was associated with memory loss, and the results of the Mendelian randomization analysis suggested a potential causal relationship between atorvastatin and memory loss 5.
• A case report published in 2006 described a 53-year-old man who experienced short-term memory loss after being treated with rosuvastatin, which resolved after discontinuation of the drug 6.
• A narrative review published in 2012 found that statin-associated cognitive impairment was a rare occurrence, and the vascular benefits and putative cognitive benefits of statins outweighed the risk of cognitive impairment 7.
• The FDA has issued safety label changes and monitoring requirements for statin therapy due to the risk of cognitive impairment, although the evidence is largely based on observational data, including case reports 8.

Mechanism of Statin-Associated Memory Changes

• The exact mechanism of statin-associated memory changes is not fully understood, but it is thought to be related to the effects of statins on cholesterol levels and the blood-brain barrier 4, 5, 7.
• Some studies have suggested that statins may affect mitochondrial function, which could contribute to memory loss 5.
• The lipophilicity of statins may also play a role, with lipophilic statins (such as simvastatin and atorvastatin) potentially being more likely to contribute to cognitive impairment due to their ability to cross the blood-brain barrier 7.

Clinical Implications

• Clinicians should be aware of the potential for statin-associated memory changes and monitor patients for cognitive impairment, particularly those with a history of cognitive decline or dementia 4, 5, 7, 8.
• If statin-associated cognitive impairment is suspected, a trial discontinuation or switching to a hydrophilic statin (such as pravastatin or rosuvastatin) may be considered 7.
• The benefits of statin therapy in reducing cardiovascular risk shouldn't be overlooked, and the current evidence does not support changing practice with respect to statin use due to the risk of cognitive impairment 7, 8.