Do Statins Increase or Decrease Alzheimer’s Risk?

Learn why statins may both increase and decrease the risk of dementia symptoms.

Is it possible for medication to both increase and decrease dementia risk? In the case of statins, this can appear to be true. Overall, the beneficial effects of statins seem to outweigh their small risk of interfering with cognitive functioning, but we can’t ignore the many reports of memory impairment associated with these medications. How can this be? There is evidence both for statin-associated brain protection and for statin-associated cognitive interference…and there is a credible explanation.

Evidence for Statins Decreasing Risk of Dementia

Statins are among the most frequently prescribed medications in the United States. Nearly one in three US adults aged 40 and older is prescribed a statin. The benefits linked with these medications are very important in fighting cardiovascular disease, which remains our leading cause of death. Statins lower low-density lipoprotein cholesterol and triglycerides. They increase high-density lipoprotein cholesterol, also known as “good” cholesterol. Statins have been convincingly shown to reduce the risk of atherosclerotic heart disease and ischemic stroke. 

Alongside their cardiovascular benefits, statins appear to modestly reduce the risk of developing Alzheimer’s dementia. Evidence for this effect is not consistent, however. Some large studies find no benefit, while others demonstrate an effect important enough to grab our attention. A 2018 analysis concluded that Alzheimer’s risk is diminished with statin use, attributing the earlier disagreements to differing approaches that researchers took in gathering and understanding their results.  

Further, a 2017 large prospective study supported the benefits of statins for reducing Alzheimer’s risk. This study deserves our attention because it was a well-controlled, randomized investigation that evaluated dementia and statin use among over 3,000 older adults every two years for an average of 6.1 years. The researchers concluded that statin use was protective against Alzheimer’s in those adults under 65, though it appeared to slightly increase Alzheimer’s risk in adults over 80 years old. 

That’s great news, but what about the reports of cognitive problems linked with statin use? 

Evidence for Statins Increasing Risk of Dementia

Alarming case reports began to accumulate in the early 2000s. A description of 60 case reports published in 2003 advised taking concerns seriously about statin-related cognitive impairment, though cognitive adverse responses were most likely uncommon. Simvastatin, atorvastatin, and pravastatin were the medications taken by the patients who were described. About half of these patients noticed cognitive problems within two months of starting treatment. The symptoms improved after drug discontinuation in about half of those affected, which is different from what would be expected of a person with Alzheimer’s disease, which is a progressive condition. 

The link between cognitive symptoms and statins is supported by a couple of additional lines of evidence. First, some patients with cognitive problems who noted improvement after stopping their statin medication experienced a recurrence when the medication was restarted. Second, a couple of small but well-designed experimental double-blind, placebo-controlled trials associated poorer performance on neuropsychological tests with the use of statins. In a description of statin effects on a couple of affected patients, the authors reminded us that a cognitive effect that looks small on neuropsychological testing can cast a much larger shadow over actual day-to-day functioning. 

How Can Statins Both Increase and Decrease Risk?

A group of researchers from Denver have tried to explain how statins could be both helpful and harmful. They note that statins, like other medications that affect metabolism in complex ways, act through more than one mechanism. Statins decrease cholesterol, and that may be an important reason for their cardiovascular benefits. Statin use reduces stroke risk, and their cerebrovascular benefits may be important in reducing dementia. There may be additional effects beyond cholesterol reduction as well. Studies have suggested that atorvastatin, for example, can reduce beta-amyloid production, reduce vascular inflammation, protect endothelial cell function, and reduce brain ischemia. 

But cholesterol is also an important structural component of the brain, enhancing brain function in multiple ways. Among other positive actions, cholesterol supports myelin sheath formation, which protects brain cells and improves their functioning, supports mitochondrial function, and promotes brain cell activity. Too great a reduction of brain cholesterol with statins that enter the central nervous system might deprive the brain of cholesterol’s beneficial effects. Given this possibility, it makes sense that the cognitive problems associated with statins may be more likely to develop in people whose brains are exposed to a higher statin level. This can result from taking a higher statin dose or having a less efficient metabolism of the medication. Some researchers suggest that the statins that more easily enter the brain because of their greater fat-solubility (lipophilicity) are more likely to affect cognitive functioning. Atorvastatin and simvastatin are lipophilic statins. 

About BrightFocus Foundation

BrightFocus Foundation is a premier global nonprofit funder of research to defeat Alzheimer’s, macular degeneration, and glaucoma. Through its flagship research programs — Alzheimer’s Disease Research, National Glaucoma Research, and Macular Degeneration Research — the Foundation has awarded nearly $290 million in groundbreaking research funding over the past 50 years and shares the latest research findings, expert information, and resources to empower the millions impacted by these devastating diseases. Learn more at brightfocus.org.   

The information provided in this section is a public service of BrightFocus Foundation, should not in any way substitute for the advice of a qualified healthcare professional, and is not intended to constitute medical advice. Although we make efforts to keep the medical information on our website updated, we cannot guarantee that the information on our website reflects the most up-to-date research.     

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