Which statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) increase the risk of dementia or memory issues?

Statins and Risk of Memory Issues/Dementia

No specific statin has been proven to increase the risk of memory issues or dementia, as current evidence does not support that statins cause cognitive dysfunction or dementia. 1, 2

Evidence on Statins and Cognitive Function

The relationship between statins and cognitive function has been extensively studied:

• Multiple high-quality guidelines consistently report no evidence linking statin use to cognitive decline or dementia 1
• Three large randomized controlled trials specifically examining cognitive function found no differences between statin and placebo groups 2
• No change in cognitive function has been reported in studies adding ezetimibe or PCSK9 inhibitors to statin therapy, even at very low LDL cholesterol levels 2, 1

The 2024 American Diabetes Association Standards of Care explicitly states that "a concern that statins or other lipid-lowering agents might cause cognitive dysfunction or dementia is not currently supported by evidence and should not deter their use in individuals at high risk for ASCVD" 2.

Rare Cognitive Side Effects

While class-wide cognitive effects are not supported by evidence, rare idiosyncratic reactions may occur:

• FDA labeling for atorvastatin notes rare reports of cognitive impairment (memory loss, forgetfulness, amnesia, confusion) associated with statin use 3
• These cognitive effects are generally:
  • Nonserious
  • Reversible upon statin discontinuation
  • Variable in onset time (1 day to years)
  • Typically resolve within a median of 3 weeks 3

Recent Research Findings

Despite the strong consensus in guidelines, some recent research has presented conflicting findings:

• A 2024 study using FDA Adverse Event Reporting System data suggested atorvastatin may be associated with memory loss 4
• However, meta-analyses have shown mixed results:
  • A Cochrane review found good evidence that statins given in late life do not prevent cognitive decline or dementia 5
  • Other meta-analyses have suggested statin use may be associated with reduced risk of dementia 6, 7

Risk-Benefit Perspective

When considering cognitive concerns, it's important to note:

• The cardiovascular event rate reduction with statins far outweighs any potential cognitive risks 1
• For every 255 patients treated with statins for 4 years:
  • 5.4 vascular events are prevented
  • Only 1 additional case of diabetes occurs 2

Clinical Approach

For patients requiring lipid-lowering therapy:

1. Assess cardiovascular risk using established guidelines
2. Do not withhold statins due to concerns about dementia
3. If a patient reports new cognitive symptoms while on statins:
   • Consider temporary discontinuation
   • Evaluate for other causes of cognitive changes
   • Consider rechallenge if appropriate

Conclusion

Based on the most recent and highest quality evidence, no specific statin has been proven to increase risk of memory issues or dementia. While rare, reversible cognitive effects can occur with any statin, these do not represent a class effect and should not deter appropriate statin use for cardiovascular risk reduction.