From the Guidelines
Statins have been shown to reduce the risk of stroke by approximately 21% through their cholesterol-lowering effects, and may also have neuroprotective effects by reducing neuroinflammation. The evidence from the American Heart Association/American Stroke Association guidelines 1 suggests that statins are effective in reducing the risk of stroke in patients with or at high risk for atherosclerosis. The guidelines recommend prescribing statins in accordance with the 2013 "ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults" 1.
Some key points to consider when prescribing statins for neuroinflammation include:
- The intensity of statin therapy depends on the drug and the dose, with examples including lovastatin at 20 mg/d (low-intensity therapy) and atorvastatin at 80 mg/d (high-intensity therapy) 1
- Statins have been shown to improve endothelial function, reduce oxidative stress, and enhance blood-brain barrier integrity, all contributing to neuroprotection 1
- The USPSTF found adequate evidence that use of low- to moderate-dose statins reduces the probability of CVD events (MI or ischemic stroke) and mortality by at least a moderate amount in adults aged 40 to 75 years who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 10% or greater 1
- Patients should be monitored for potential side effects including myalgia, liver enzyme elevations, and rarely cognitive effects, particularly in elderly patients
The mechanism of statins' neuroprotective effects involves not only HMG-CoA reductase inhibition but also suppression of isoprenoid intermediates that regulate inflammatory signaling pathways. Statins have demonstrated anti-inflammatory properties in the central nervous system by inhibiting microglial activation and reducing pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6. Typical doses that have shown neuroinflammatory benefits include atorvastatin 10-80 mg daily, simvastatin 20-40 mg daily, or rosuvastatin 5-20 mg daily. However, the full clinical significance of these neuroinflammatory effects remains under investigation, and statin therapy should be primarily guided by cardiovascular risk rather than neurological indications alone.
From the Research
Statins and Neuroinflammation
- Statins have been found to significantly attenuate both the clinical symptoms of neuroinflammation and the associated infiltration of inflammatory cells into the CNS 2.
- The precise mechanism by which statins exert this inhibitory effect on leukocyte infiltration and consequential neuroinflammatory disease is presently unclear, but several potential mechanisms have been proposed 2.
- Statins have additional properties such as endothelial protection, antioxidant, anti-inflammatory, and anti-platelet effects, which may have potential therapeutic implications in neurological disorders 3.
- Compelling clinical and preclinical studies have shown the neuro-protective efficacy of statins in various neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and primary brain tumors 3.
Effects of Statins on Neuroinflammation
- Statins have been found to reduce the levels of low-density lipoproteins and cholesterol, which may contribute to their anti-inflammatory effects 2.
- The anti-inflammatory effects of statins may be independent of their cholesterol-lowering action, and several mechanisms have been proposed to explain this effect 2, 3.
- Statins may also have a role in modulating the immune response and reducing the infiltration of inflammatory cells into the CNS 2.
Clinical Implications
- The effectiveness of statins in treating neurological disorders such as stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and primary brain tumors needs to be conclusively proven in vivo and/or in adequate clinical trials 3.
- The benefit-harm profile of statins differs by statin type, and a quantitative assessment of the benefit-harm balance is needed to inform whether statins provide net benefit 4.
- Statins may have a dichotomous role in neuropathic pain, with preclinical studies suggesting a beneficial effect and clinical evidence suggesting a potential pain-inducing role 5.