Cross-sectional relationships of serum 25-OH-D metabolite of vitamin D with cognition and mood in a Cognitively-Healthy older cohort

Background: Previous cross-sectional studies have concluded that the positive relationship between vitamin D status and cognition may reflect reverse causality, that is, low vitamin D status results from cognitive decline, associated behaviours and comorbidities, and not the reverse. The present study therefore investigated relationships between total 25-OH-D (25-OH-D3 plus 25-OH-D2) and 15 integrated scores of cognition and mood cognitively-normal, healthy elderly subjects. Methods: The study was cross-sectional and based in Adelaide, South Australia (lat: 34.93°S) during summer months of 2008. Participants, from the Older People, Omega-3 and Cognitive health (EPOCH) Study (ACTRN12607000278437), were community-dwelling (N=387), 65 to 90 years (mean 73.1), 54% female and cognitively normal at baseline (MMSE>24). Blood sampling, cognition and mood testing at a single timepoint occurred from January to April. Participants were characterised by multiple biometric and clinical measures and bloods were analysed for 25-OH-D3 and 25-OH-D2, homocysteine, C-reactive protein and malondialdehyde. Results: Based on a cut-off of75 nM 25-OH-D, 44% of participants were considered deficient. Fully adjusted models controlling for all parameters significantly associated with vitamin D status or cognition/mood measure demonstrated that 25-OH-D was significantly related to one cognition (Reasoning Speed, p=0.03) and two mood measures (General Positive Affect, and p=0.02; Attentiveness, p=0.02). Additional relationships were present for sub-populations based on gender, vitamin D sufficiency and APOE genotype. Conclusion: The positive relationships between vitamin D status and selected brain functions observed within this cognitively healthy cohort support a causal, protective role of vitamin D in brain function however, clinical substantiation is required.