Vitamin D in the elderly and its relationship to inflammation and cognitive health

Background: There is a major shift in ageing demographics as individuals are experiencing increased longevity. This shift may be beneficial for the individual who will live into more advanced year than their ancestors. However, this demographic shift also has an economic health burden in the form of age-related chronic diseases healthcare costs. The healthcare costs are estimated to increase significantly from the ?3 billion currently being spent annually for the treatment of dementia and experts estimate the global cost will soon reach over one trillion dollars (Prince et al. 2016). In 2017 PHE reported that dementia was the leading cause of mortality in older adults, exceeding CVD, stroke and lung cancer for the first time. The most common form of dementia is Alzheimer disease accounting for approximately 62% of cases, while other forms include vascular dementia, mixed Lewy body dementia, and frontotemporal dementia. There is currently no cure for dementia and few treatments. Although there is relatively little known of the aetiology of dementia, it is thought to be largely multifactorial with a long preclinical phase prior to symptoms presenting themselves. Some research has shown inflammation to contribute to cognitive decline, and certain dietary nutrients have also being identified as possible modifiable risk factors. One such nutrient identified is vitamin D. Many previous studies have suggested that vitamin D exerts its beneficial effects on cognitive health through anti-inflammatory and immunomodulatory pathways. However, no studies have examined vitamin D for effects exclusive to these pathways. Objective: The aim of this study was to explore the association between vitamin D status and cognition in community dwelling older Irish adults. A secondary aim was to investigate if vitamin D mediates cognitive integrity through inflammatory pathways or if it exerts an association independent of inflammation. This will be addressed through statistical adjustment for the presence of inflammation. This study also aims to assess whether vitamin D can predict incidence cognitive decline over 5+ years follow-up period. Design, setting, and participants: This observational cross ? sectional and longitudinal cohort study enrolled 1000 older Irish adults (>60 yrs at baseline) 5 years following baseline (n=5186). Recruitment took place in Northern Ireland and Dublin as part of the Trinity, Ulster, Department of Agriculture (TUDA) ageing cohort follow-up study. Outcomes measured: Participants were examined for anthropometric measures, lifestyle factors, medical history, current medication, cognition (MMSE, FAB, RBANS), dietary, inflammatory markers and cytokine concentrations (CRP, IL-6, TNF-alpha, IL-10), and vitamin D status by liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: Partial correlation shows that 25(OH)D is positively associated with cognition when assessed by MMSE and RBANS Index II score (P<0.05 for both). Furthermore, IL-6 significantly negatively correlates with RBANS index III (P<0.05 ) index V (P<0.05), and total scale (P