Does HMG-CoA reductase inhibitor (statin) cause cognitive impairment, specifically memory loss?

From the Guidelines

There is no strong evidence that statins cause memory loss, and the benefits of statins in preventing heart attacks and strokes typically outweigh potential side effects for people at risk of cardiovascular disease. While some patients have reported memory problems while taking statins, large clinical studies have not found a consistent link between statin use and cognitive decline, as reported in the most recent study [ 1 ]. In fact, some research suggests statins may actually help protect brain function by reducing the risk of stroke and vascular dementia. Common statin medications include atorvastatin (Lipitor), rosuvastatin (Crestor), simvastatin (Zocor), and pravastatin (Pravachol).

Some key points to consider:

• The most recent systematic review of the U.S. Food and Drug Administration’s (FDA’s) postmarketing surveillance databases, randomized controlled trials, and cohort, case-control, and cross-sectional studies evaluating cognition in patients receiving statins found that published data do not reveal an adverse effect of statins on cognition [ 1 ].
• No change in cognitive function has been reported in studies with the addition of ezetimibe or PCSK9 inhibitors to statin therapy, including among individuals treated to very low LDL cholesterol levels [ 1 ].
• The U.S. Food and Drug Administration postmarketing surveillance databases have also revealed a low reporting rate for cognitive-related adverse events, including cognitive dysfunction or dementia, with statin therapy, similar to rates seen with other commonly prescribed cardiovascular medications [ 1 ].

If you experience memory issues while taking a statin, don't stop the medication abruptly but discuss your concerns with your healthcare provider. They might consider switching you to a different statin or adjusting your dose. Memory concerns should be evaluated individually, as many factors including aging, stress, and other medications can affect cognitive function [ 1 ]. Statins work by blocking an enzyme in the liver that produces cholesterol, thereby reducing levels of harmful LDL cholesterol in the bloodstream.

From the FDA Drug Label

Rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. Cognitive impairment was generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks) 2 Rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. Cognitive impairment was generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks) 3 Statin use may cause memory loss in some patients.

• The incidence of memory loss is not well established, but it is considered a rare adverse reaction.
• Cognitive impairment associated with statin use is generally nonserious and reversible upon statin discontinuation.
• The time to symptom onset can vary from 1 day to years, and the time to symptom resolution is typically around 3 weeks after statin discontinuation.

From the Research

Statin-Associated Memory Loss

• There have been reports of statin-associated memory loss, as seen in a case study where a 51-year-old man experienced delayed-onset, progressive memory loss while receiving simvastatin for hypercholesterolemia 4.
• The memory loss resolved gradually over the next month after switching to pravastatin, suggesting a possible link between simvastatin and cognitive decline.

Effects of Statins on Cognition

• Early studies have shown that statin use may lead to mild reversible cognitive decline, although long-term studies have shown inconclusive findings 5.
• Some studies suggest that statins may have a protective effect on cognition, particularly in reducing the risk of cerebrovascular disease, which may in turn reduce the risk of mild cognitive decline and dementia 5, 6.
• However, other studies have found evidence of statin-induced cognitive decline, with possible mechanisms including reduction of coenzyme Q10 synthesis and depletion of central nervous system myelin 7.

Factors Modifying the Cognitive Effects of Statins

• Individual and statin-related factors, such as age, comorbidities, and type of statin, may modify the cognitive effects of statins 8.
• The relationship between statins and cognitive function is complex, and more research is needed to understand the underlying mechanisms and to determine the association between statin use and cognitive decline 8, 6.

Discrepancies in Study Findings

• Discrepancies in study findings may be due to methodological differences, and evaluation of all studies indicates that statin-associated cognitive decline is a real entity 7.
• Further research is needed to better understand the effects of statins on cognition and to determine the potential benefits and risks of statin use in different populations 5, 8, 6.