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

Low vitamin D status has been linked to adverse cognitive outcomes in older adults. How-ever, 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-sec-tional 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 demo-graphic, 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 ex-tending through to older ages may help to clarify the nature, strength, and temporality of these relationships.