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

Int J Environ Res Public Health. 2021 Dec 31;19(1):450. doi: 10.3390/ijerph19010450.


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.

Keywords: 25-hydroxyvitamin D; cognitive ageing; cognitive performance; domain-specific cognition; global cognition; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cognition
  • Cross-Sectional Studies
  • Female
  • Healthy Aging*
  • Humans
  • Male
  • Middle Aged
  • Vitamin D
  • Vitamin D Deficiency*
  • Vitamins


  • Vitamins
  • Vitamin D