What is the relationship between statin (HMG-CoA reductase inhibitor) therapy and dementia?

From the Guidelines

The current evidence suggests that statin therapy does not increase the risk of dementia and may even have a neutral to potentially beneficial effect on cognitive function. The relationship between statin therapy and dementia has been extensively studied, and the most recent evidence indicates that statins do not cause cognitive impairment or dementia 1. In fact, several large randomized trials have shown no differences in cognitive function between statin and placebo groups 1. Additionally, the use of ezetimibe or PCSK9 inhibitors in combination with statin therapy has not been associated with any adverse effects on cognitive function 1.

Some key points to consider when evaluating the relationship between statin therapy and dementia include:

• The lack of evidence supporting an adverse effect of statins on cognition, as reported in a systematic review of postmarketing surveillance databases, randomized controlled trials, and cohort, case-control, and cross-sectional studies 1
• The potential benefits of statins in reducing vascular disease risk factors and possibly through direct effects on brain pathology, including reducing inflammation and amyloid formation
• The importance of weighing the cardiovascular benefits of statins against any potential cognitive risks, particularly in patients with established cardiovascular disease or at high risk

In terms of clinical practice, standard statin dosing should be continued in patients with or at risk for cardiovascular disease, regardless of dementia concerns. If cognitive symptoms develop after starting a statin, clinicians might consider a trial of a different statin or temporary discontinuation to determine if symptoms improve, while weighing cardiovascular benefits 1. Overall, the evidence suggests that statin therapy can be safely used in patients with or at risk for dementia, without increasing the risk of cognitive decline.

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 Therapy and Dementia: There is no direct evidence in the provided drug labels that supports a causal relationship between statin therapy and dementia. However, rare postmarketing reports of cognitive impairment associated with statin use have been noted.

• Key Points:
  • Cognitive impairment is generally nonserious and reversible upon statin discontinuation.
  • The time to symptom onset and resolution varies.
• Clinical Decision: Given the limited and indirect evidence, it is essential to approach this topic with caution and consider individual patient factors when making clinical decisions regarding statin therapy and potential cognitive impairment.

From the Research

Relationship Between Statin Therapy and Dementia

• The relationship between statin therapy and dementia is complex and has been the subject of numerous studies 4, 5, 6, 7, 8.
• Some studies suggest that statin use may be associated with a reduced risk of dementia, particularly Alzheimer's disease 5, 7.
• A meta-analysis of observational studies found that statin use was associated with a lower risk of all-cause dementia, Alzheimer's disease, and vascular dementia 7.
• Another study found that the use of pravastatin and rosuvastatin in combination with renin-angiotensin system (RAS)-acting antihypertensives may reduce the risk of Alzheimer's disease and related dementias 8.

Effects of Statin Therapy on Cognitive Decline and Dementia Progression

• A study found that ongoing statin use was not associated with cognitive decline or dementia progression in older adults with mild-moderate Alzheimer's disease 6.
• Another study found that statin use was not associated with a significant difference in adverse events, including cognitive decline and dementia progression, in patients with dementia 4.

Subgroup Analyses and Statin Type

• Subgroup analyses have found that certain statins, such as rosuvastatin, may have a more pronounced protective effect against dementia 7.
• The combination of statins with antihypertensive therapy, particularly RAS-acting antihypertensives, may also have a protective effect against dementia 8.

Limitations and Future Research

• The current evidence is largely based on observational studies, and randomized controlled trials are needed to confirm the findings 4, 5, 6, 7, 8.
• Further research is needed to explore the effects of statin therapy on cognitive decline and dementia progression in different patient populations and to determine the optimal statin regimen for dementia prevention.