Associations of modifiable and non-modifiable risk factors with cognitive functions – a prospective, population-based, 17 years follow-up study of 3,229 individuals

Abstract Background 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 aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. Methods Participants from a large, prospective, population-based, Swedish study were included ( n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA 1c ), 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. Results The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3–20.8) years. When examining independent effects, APOE ε4 genotype( p < 0.01), and higher HbA 1c ( p < 0.001), were associated with future low memory function. Higher BMI ( p < 0.05), and HbA 1c ( p < 0.05), lower high-density lipoprotein cholesterol (HDL-C)( p < 0.05)and stroke( p < 0.001) 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. Further, significant interaction effects between predictors and APOE genotype were found. For memory function, the protective effects of education were greater among ɛ4-carriers( p < 0.05). For attention/executive function, the protective effects of alcohol were greater among ɛ2 or ɛ4-carriers( p < 0.05). Also, attention/executive function was lower among ɛ4-carriers with higher BMI( p < 0.05) and ɛ2-carriers with higher HbA1c-levels( p < 0.05). Conclusions 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. 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. Having detailed knowledge about the specific cognitive effects of different risk factors might be beneficial in preventive health counseling.