The relationship of neuroticism to amyloid and tau pathologies in cognitively normal older adults

Abstract

AbstractBackgroundPrior work has shown that individuals with higher levels of neuroticism are at an increased risk of developing Alzheimer’s Disease (AD). Increasing evidence has indicated an association of increased neuroticism to increased amyloid‐beta (Aβ) and tau burdens, suggesting that this personality trait is a risk factor for increased pathological accumulations. However, the cross‐sectional nature of these studies do not offer the ability to infer causality. Here, we replicate and extend upon previous work, assessing the relationship of neuroticism to AD pathologies in 60 older adults across three time‐points.MethodThis study included 60 cognitively normal participants from the Dallas LifeSpan Brain Study, aged 50+, that completed three time‐points of cortical Aβ scanning and a baseline personality assessment. Linear regressions were used to model the relationship of neuroticism to cortical Aβ burden (n = 60) and cortical tau burden (n = 48). Utilizing linear mixed effects models, neuroticism was used to predict cortical Aβ accumulation over 7‐10 years.ResultWe found that the effects of neuroticism on AD pathologies differs by brain regions and facets of neuroticism. Most notably, increased neuroticism predicted increased global Aβ burden (p = .042) beyond the effects of baseline age, sex, education, and depressive symptoms. When we further investigated this relationship using the facets comprising the neuroticism score, only the anger‐hostility facet of neuroticism predicted increased global Aβ burden (p = .003). Regional investigations demonstrated a significant effect of neuroticism on Aβ burden in the anterior cingulate cortex (p = .028), lateral parietal cortex (p = .035), and the posterior cingulate cortex (p = .021) and a trending effect in the dorsolateral prefrontal cortex (DLPFC) (p = .054). Contrary to our hypotheses, we did not find a significant effect of neuroticism on global or regional Aβ accumulation. Tau analyses detected an effect of neuroticism on tau burden in the DLPFC (p = .03), a predetermined region of interest. Additionally, only the anger‐hostility facet of neuroticism significantly predicted global tau burden (p = .036).ConclusionThis work demonstrates that certain regions of the brain may be at an increased risk for AD pathologies in individuals with higher neuroticism. Specific facets of neuroticism, such as anger‐hostility, may also confer additional risk for these augmented accumulations.