Do statins increase your risk of dementia

I had lunch with a friend recently whose mother has dementia. My friend takes a statin to lower her risk of cardiovascular disease, but she expressed concerns about reports that statins might increase the risk of developing dementia. I lost my father to dementia, so any potential increased risk of dementia from statins is highly concerning to me as well. In 2012, the FDA issued a label change to statins that stated, “Memory loss and confusion have been reported with statin use. These reported events were generally not serious and went away once the drug was no longer being taken.” This label change was based post-marketing surveillance in which cases of ill-defined memory loss or cognitive impairment had been reported. What does current evidence suggest?

Earlier this year, two systematic reviews and meta-analyses were published evaluating statin use and dementia. Filho et al reviewed 55 observational studies that included over 7 million patients and found a slightly decreased risk of all types of dementia with statin use. Rosuvastatin (Crestor) was associated a 28% reduction in dementia ((HR 0.72; 95% CI: 0.60 to 0.88). Similarly, Du et al found similar results in their review of 42 studies that included over 6 million patients. They reported that most studies suggested that higher dosages and longer exposure duration of statins further reduce the risk of dementia and Alzheimer’s disease. While this suggests statins may be protective, observational studies can only report associations, not causation, due to confounding variables.

It would be nice if we also had randomized controlled clinical trial (RCT) data to evaluate if statins increase dementia risk. Fortunately, we do. The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was a randomized, placebo-controlled trial that evaluated pravastatin 40 mg daily in 5,804 individuals aged 70–82 years with or at risk for vascular disease. Cognitive function was assessed repeatedly using multiple neuropsychological tests and no difference in cognitive decline was observed between the pravastatin and placebo groups across any cognitive domain. Pravastatin had no significant effect on the risk of dementia or cognitive impairment compared to placebo over the 3 year study period.

The Heart Protection Study (HPS) was a large RCT that evaluated the effects of simvastatin 40 mg daily versus placebo in 20,536 adults aged 40–80 years at high risk for vascular events. Cognitive function was specifically assessed in a substantial subset of participants, including those over age 70, to determine whether statin therapy increased the risk of cognitive impairment or dementia. This trial also found no significant difference in the frequency of cognitive impairment or dementia between the simvastatin and placebo groups over the 5 year study period.

The Heart Protection Study (HPS) was a large RCT that evaluated the effects of simvastatin 40 mg daily versus placebo in 20,536 adults aged 40–80 years at high risk for vascular events. Cognitive function was specifically assessed in a substantial subset of participants, including those over age 70, to determine whether statin therapy increased the risk of cognitive impairment or dementia. This trial also found no significant difference in the frequency of cognitive impairment or dementia between the simvastatin and placebo groups over the 5 year study period.

Lastly, the HOPE-3 (Heart Outcomes Prevention Evaluation-3) trial was a large RCTthat evaluated the effects of rosuvastatin 10 mg daily, blood pressure lowering (candesartan/hydrochlorothiazide), or their combination on cardiovascular and cognitive outcomes in an ethnically diverse population of older adults at intermediate cardiovascular risk, without known cardiovascular disease. In the cognitive substudy, participants aged ≥70 years underwent serial cognitive assessments over a median follow-up of 5.7 years. Across multiple cognitive domains—including executive function, memory, and global cognition—no significant differences were observed between the statin and placebo groups. Rosuvastatin therapy did not significantly affect cognitive decline or the risk of dementia compared to placebo.

In summary, these 3 RCT’s of 3 different statins did not find that statin use increases the risk of dementia. The American Heart Association guidelines state: “The issue has also been examined in several overviews of both RCTs and observational data, with no conclusive evidence for either cognitive benefit or harm from statin therapy.” The American Diabetes Association guidelines agree: “a concern that statins or other lipid-lowering agents might cause cognitive dysfunction or dementia is not currently supported by evidence.

I told my friend to keep taking her statin.