Investigating Potential Dose–Response Relationships between Vitamin D Status and Cognitive Performance: A Cross-Sectional Analysis in Middle- to Older-Aged Adults in the Busselton Healthy Ageing Study

Abstract

Low vitamin D status has been linked to adverse cognitive outcomes in older adults. However, relationships at higher levels remain uncertain. We aimed to clarify patterns of association between vitamin D status and cognitive performance, using flexible regression methods, in 4872 middle- to older-aged adults (2678 females) from the Busselton Healthy Ageing Study. Cross-sectional associations of serum levels of 25-hydroxyvitamin D (25OHD) and performance in cognitive domains were modelled using linear regression and restricted cubic splines, controlling for demographic, lifestyle, and health factors. Mean ± SD serum 25OHD levels were 78 ± 24 nM/L for women and 85 ± 25 nM/L for men. Increasing levels in women were associated with better global cognition (linear trend, p = 0.023) and attention accuracy (continuity of attention), with improvement in the latter plateauing around levels of 80 nM/L (nonlinear trend, p = 0.035). In men, increasing levels of serum 25OHD were associated with better attention accuracy (linear trend, p = 0.022), but poorer semantic verbal fluency (linear trend, p = 0.025) and global cognition (nonlinear trend, p = 0.015). We identified patterns of association between serum 25OHD levels and cognitive performance that may reflect early dose–response relationships, particularly in women. Longitudinal analyses extending through to older ages may help to clarify the nature, strength, and temporality of these relationships.