Is neuroticism differentially associated with risk of Alzheimer's disease, vascular dementia, and frontotemporal dementia?

This study examines whether neuroticism is differentially associated with risk of incident Alzheimer's disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD) using a prospective study design. Participants from the UK Biobank (N = 401,422) completed a self-report neuroticism scale in 2006-2010 and incident all-cause dementia, AD, VD, and FTD were ascertained using electronic health records or death records up to 2018. During an average follow-up of 8.8 years (3,566,123 person-years), there were 1798 incident of all-cause dementia, 675 AD, 376 VD, and 81 FTD. Accounting for age and sex, compared to individuals in the low quartile, individuals in the top quartile of neuroticism had higher risk of all-cause dementia (HR = 1.70; 95% CI: 1.49-1.93), AD (HR = 1.42; 1.15-1.75), VD (HR = 1.73; 1.30-2.29), but not FTD (HR = 0.89; 0.49-1.63). The associations with AD and VD were attenuated but remained significant after further accounting for education, household income, deprivation index, diabetes, hypertension, stroke, heart attack, ever smoker, physical activity, obesity, hemoglobin A1c, C-reactive protein, and low-density lipoprotein. The associations were not moderated by socioeconomic status. The findings were consistent in analyses that excluded cases that occurred within the first 5 years of follow-up. In conclusion, neuroticism is a robust predictor of incident AD and VD, but not FTD. This pattern suggests that the affective symptoms that distinguish dementia types may partly reflect premorbid differences in trait neuroticism.