Are lipid-lowering drugs harmful to cognitive performance?: A Mendelian randomization study

Area of Science:

• Cardiovascular disease research
• Neuroscience
• Pharmacogenomics

Background:

• Cardiovascular disease (CVD) is a leading cause of death globally and is linked to cognitive impairment in older adults.
• Lipid-lowering drugs are crucial for CVD management, but their impact on cognition remains debated due to conflicting research.
• Understanding the precise effects of different lipid-lowering drug classes on cognitive function is essential for clinical practice.

Purpose of the Study:

• To investigate the causal relationship between various lipid-lowering drugs and cognitive performance using a Mendelian randomization approach.
• To provide evidence-based guidance for clinicians in selecting appropriate lipid-lowering therapies concerning cognitive side effects.
• To differentiate the cognitive impact of commonly prescribed lipid-lowering medications.

Main Methods:

• A 2-sample Mendelian randomization study utilizing genome-wide association study summary statistics.
• Instrumental variables were single-nucleotide polymorphisms associated with lipid levels (LDL cholesterol, triglycerides) and drug target genes.
• Proxies were used for statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and fibrates.

Main Results:

• Genetically predicted use of statins showed an adverse effect on cognitive performance (β = -0.094, P < .001).
• Ezetimibe use was also associated with a significant adverse effect on cognition (β = -0.319, P < .001).
• No significant impact on cognitive performance was observed for PCSK9 inhibitors and fibrates.

Conclusions:

• Statins and ezetimibe may negatively influence cognitive function, necessitating careful consideration during prescription.
• PCSK9 inhibitors and fibrates appear to have a neutral effect on cognition, offering safer alternatives for certain patient groups.
• Further long-term clinical studies are required to validate these findings and inform clinical guidelines on lipid-lowering drug selection for cognitive health.