Intensive LDL-cholesterol lowering therapy and neurocognitive function

Abstract

The key lipid-lowering target is to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) levels, usually by using statins. The new treatment strategies for lipid-lowering therapy include using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as an exciting approach to reduce residual risk of cardiovascular diseases (CVD). However, concerns about possible adverse effects, including neurocognitive disorders, were issued by the Food and Drug Administration (FDA). The current disputable evidence does not allow definite conclusions as to whether statins contribute to, or cause, clinically meaningful cognitive impairment. Some evidence indicates a high rate of memory loss, while other evidence suggests a benefit in dementia prevention. This debate should not discourage appropriate statin and other lipid-lowering drug administration. However, prescribers should be aware of such potential drug-related side effects. Prospective controlled studies comparing the short- and long-term effects of different statins on cognitive function are warranted. The effects of intensive LDL-C lowering on neurocognition might be attributed to an off-target effect. It is also possible that pre-existing pathology and vascular risk may already be present outweighing any effect related to lipids. Gender, genetic, LDL-C-related genotypes and aging-related changes should also be considered. Some data indicate that carriers of apolipoprotein E (apoE) ε-4 allele, with low levels of apoA1 and high-density lipoprotein cholesterol have a distinct plasma lipid profile and may be more susceptible to neurocognitive dysfunction. Future research on lipid-lowering drugs and cognition is needed; careful study design and analysis will be critical.