Associations of modifiable and non-modifiable risk factors with cognitive functions

Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype were assessed. (The three main alleles of the APOE gene (ε4, ε3 and ε2) carry differential risks for conditions including Alzheimer’s disease (AD) and cardiovascular disease).
The research was based on 3,229 participants from a large, prospective, population-based, Swedish study. Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA1c), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions.
The mean age at baseline was 56.1years and 59.7% were women. The mean follow-up time was 17.4 years. When examining independent effects, APOE ε4 genotype and higher HbA1c, were associated with future low memory function. Higher BMI and HbA1c lower high-density lipoprotein cholesterol (HDL-C) and stroke were associated with future low attention/executive function. The strongest factors associated with both better memory and attention/executive functions were higher education and alcohol consumption. Significant interaction effects between predictors and APOE genotype were found. For memory function, the protective effects of education were greater among ε4-carriers. For attention/executive function, the protective effects of alcohol were greater among ε2 or ε4-carriers. Also, attention/executive function was lower among ε4-carriers with higher BMI and ε2-carriers with higher HbA1c-levels.
Targeting cardiovascular risk factors in mid-life could have greater effect on future attention/executive functions rather than memory, whereas targeting diabetes could be beneficial for multiple cognitive domains, the researchers conclude. In addition, effects of different risk factors may vary depending on the APOE genotype. The varied cognitive profiles suggest that different mechanisms and brain regions are affected by the individual risk factors. Source: Glans, I., Nägga, K., Gustavsson, AM. et al. Associations of modifiable and non-modifiable risk factors with cognitive functions – a prospective, population-based, 17 years follow-up study of 3,229 individuals. Alz Res Therapy 16, 135 (2024).