Apolipoprotein E e4 and Cognitive Function: A Modifiable Association Results from Two Independent Cohort Studies

Area of Science:

• Neuroscience
• Genetics
• Cardiology

Background:

• The apolipoprotein E (APOE) e4 genetic polymorphism is a significant risk factor for Alzheimer's disease.
• Understanding and mitigating the cognitive effects of APOE e4 is crucial for disease prevention.

Purpose of the Study:

• To investigate the interaction between APOE e4, hypercholesterolemia, and cardiovascular disease on cognitive performance.
• To explore potential modifiable risk factors that influence the detrimental effects of APOE e4 on cognition.

Main Methods:

• Linear regression models were used to analyze cognitive performance in two independent cohorts (n=1,434 and n=366).
• Restricted cubic splines assessed dose-response relationships between serum cholesterol and cognition, stratified by APOE genotype.
• The study examined interactions between APOE genotype, hypercholesterolemia, and cardiovascular disease.

Main Results:

• The negative impact of APOE e4 on cognition was significantly amplified by hypercholesterolemia and cardiovascular disease in both cohorts.
• Hypercholesterolemia affected cognitive function only in APOE e4 carriers with cardiovascular disease.
• A statistically significant interaction was observed between APOE genotype and hypercholesterolemia in both study groups.

Conclusions:

• The adverse effects of the APOE e4 polymorphism on cognitive function are strongly influenced by modifiable risk factors.
• Managing hypercholesterolemia and cardiovascular disease may be key to preventing cognitive decline in APOE e4 carriers.