Vitamin D and Alzheimer’s: what is the connection?

Vitamin D is a fascinating molecule. In the body it is involved in a multitude of biological processes, and current research is constantly uncovering new associations between vitamin D deficiency and severe disease.

The connection between vitamin D and neurodegenerative diseases such as Alzheimer’s disease and other forms of dementia has been the subject of research for many years. Several studies have indeed found a connection, namely that low serum concentrations of the storage form of 25-OH vitamin D seem to be associated with an increased risk of developing Alzheimer’s disease. Up until now it was not clear if the vitamin D deficiency contributes to Alzheimer’s disease or if Alzheimer’s disease causes the vitamin D deficiency. A new prospective and population-based study which has just been published in the journal Neurology appears to confirm the first hypothesis.

A total of 1658 adults with an average age of 73 took part in the study in the USA. At the start of the study they were all healthy, with no neurological or cardiovascular preconditions. 25-OH vitamin D concentrations were determined in serum at the start of the study, and the cognitive capabilities of the participants were assessed after an average of 5.6 years using defined criteria of the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association. The result: 171 participants developed a form of dementia in the elapsed time, of these 102 had Alzheimer’s disease. The risk was elevated by 60 to 120% for participants with a 25-OH vitamin D concentration of under 50 nmol/L (corresponding to around 20 ng/ml) compared to participants with sufficient vitamin D provision. Moreover, the more severe the deficiency, the higher the risk.

So how could a vitamin D deficiency be connected to the development of dementia? 25-OH vitamin D is converted by the enzyme 1-a-hydroxylase into 1,25-dihydroxy vitamin D (calcitriol), which represents the biologically active form of vitamin D. Complexed with vitamin D receptors (VDR) and other cofactors, calcitrol acts as a transcription factor and influences the expression of a multitude of genes. Both the enzyme and VDR are expressed in the brain, suggesting that calcitrol has a direct effect on neuronal tissue in the brain. In vitro, it regulates the synthesis of different neurotrophic factors (NGF, NT3, NT4, GDNF), which in turn stimulate the differentiation and growth of nerve cells. In addition, calcitrol suppresses the induction of the enzyme “inducible nitric monoxide synthase” and the cytotoxicity of the characteristic amyloid plaques in cortical neurons. Both of these factors play a significant role in the pathogenesis of Alzheimer’s disease. Lastly, a connection between vitamin D and vascular diseases has been described. These could also cause dementia through disrupted blood circulation and undersupply of the brain.

The authors of the publication conclude that vitamin D deficiency significantly increases the risk of developing dementia. An inverse causality (dementia as the cause of vitamin D deficiency) seems to be unlikely, since the participants did not show any relevant diseases at the beginning of the study. However, further studies are necessary to reproduce the results and to elucidate the exact relationship between vitamin D deficiency and neurodegenerative diseases.

Litteljohns TJ et al., Neurology 2014, 83(10): 920-928.

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