Vitamin D and cognitive function

Abstract

The role of vitamin D in skeletal health is well established, but more recent findings have also linked vitamin D deficiency to a range of non-skeletal conditions such as cardiovascular disease, cancer, stroke and metabolic disorders including diabetes. Cognitive impairment and dementia must now be added this list. Vitamin D receptors are widespread in brain tissue, and vitamin D's biologically active form [1,25(OH)₂D3] has shown neuroprotective effects including the clearance of amyloid plaques, a hallmark of Alzheimer's Disease. Associations have been noted between low 25-hydroxyvitamin D [25(OH)D] and Alzheimer's disease and dementia in both Europe and the US. Similarly, the risk of cognitive impairment was up to four times greater in the severely deficient elders (25(OH)D < 25 nmol/L) in comparison with individuals with adequate levels (≥ 75 nmol/L). Further studies have also shown associations between low 25(OH)D concentrations and cerebrovascular events such as large vessel infarcts, risk of cerebrovascular accident and fatal stroke. Cross-sectional studies cannot establish temporal relationships because cognitive decline and the onset of dementia itself may influence vitamin D concentrations through behavioural and dietary changes. However, two large prospective studies recently indicated that low vitamin D concentrations may increase the risk of cognitive decline. Large, well designed randomized controlled trials are now needed to determine whether vitamin D supplementation is effective at preventing or treating Alzheimer's disease and dementia.

Key Words::

• Alzheimer's disease
• dementia
• cognition
• cognitive decline
• calcitriol

Acknowledgements

Drs Llewellyn and Lang are supported by the UK National Institute for Health Research (NIHR)-funded Peninsula Collaboration for Leadership in Applied Health Research and Care. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. This work is also supported by grants from the Alzheimer's Association (NIRG-11 - 200737), the James Tudor Foundation, the Sir Halley Stewart Trust, the Norman Family Charitable Trust, the Peninsula Medical School Foundation and the Age Related Diseases and Health Trust. The sponsors were not involved in the data collection, analysis, interpretation, writing or review of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this article.

Questions and answers

M Curti, Switzerland

Have there been attempts to compare cognitive function in elderly people from countries where nutrition is fortified with vitamin D and those where it is not fortified?

D Llewellyn

Yes, cross-national direct comparisons for cognitive function are very tricky technically. We have data from NHANES in the US where levels of fortification are very different from what we see in the UK or in Italy. The region studied in Italy is very rural where fortification levels are very low. There is data suggesting that dietary intake is linked with cognition in older adults which is surprising as levels were relatively modest, from a study published by a French group in 2011.

E Schleicher, Germany

I wonder if vitamin D crosses the blood-brain barrier?

D Llewellyn

Yes, it does but we do not have any large studies looking at the concentrations in CSF in relation to clinical diagnosis. There have been some small exploratory studies suggesting a link with diagnosis rather than just its presence.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.