Relationships between heritable dementia risk factors, cardiovascular risk factors in young adulthood, and midlife neuropsychological outcomes

Abstract

Background Selected cardiovascular factors, APOE4 carriership, and family history (FH) are robust risk factors for Alzheimer’s disease and dementia. While cardiovascular risk tends to affect cognition from midlife, it remains unclear whether heritable risk predicts cardiovascular health in young adulthood and midlife, and whether young-adult cardiovascular health predicts midlife cognition. Objective We sought to examine how heritable dementia risk relates to cardiovascular health and how these cardiovascular risk factors in young adulthood predict midlife brain volumes and cognition. Methods We used data from the CARDIA study, which followed 5115 individuals aged 18-30 at baseline over 30 years. Analyses focused on 2808 participants (Mean age = 60, SD = 3.58) who attended the 30-year visit. We examined associations between APOE4 and FH with baseline and 30-year follow-up measures of cardiovascular risk factors (LDL-C, HDL-C, glucose, blood pressure, body mass index (BMI), smoking), cognition, and brain volumes. Results APOE4 carriers with FH had higher LDL-C and lower HDL-C levels as early as young adulthood, persisting into midlife. BMI and smoking were the only cardiovascular risk factors from young adulthood that predicted midlife cognition. There was no association between young adult cardiovascular risk factors and midlife brain volumes, but those with heritable dementia risk had larger brain volumes in regions vulnerable to midlife atrophy. Conclusions APOE4 carriership was associated with an unfavourable lipid profile that started in early adulthood and persisted to later life. Early cardiovascular risk was also associated with midlife cognition, which is earlier than studies typically focusing on later-life cognition