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Study supports link between low vitamin D and dementia risk

BMJ 2014; 349 doi: (Published 07 August 2014) Cite this as: BMJ 2014;349:g5049
  1. Michael McCarthy
  1. 1Seattle

Being severely deficient in vitamin D is associated with a more than twofold increased risk of developing dementia, a new study has found.1 The study appeared in the journal Neurology, and the lead author was Thomas J Littlejohns of the University of Exeter Medical School in the United Kingdom.

In the study the researchers analysed data from 1658 elderly US residents who had participated in the Cardiovascular Health Study—a prospective, population based study conducted in the 1990s to look at cardiovascular disease risks.

The participants selected for the new analyses had all been ambulatory when they enrolled in the Cardiovascular Health Study, they had been free of dementia, cardiovascular disease, and any history of transient ischemic attacks or stroke, and they had had their serum 25 hydroxyvitamin D (25(OH)D) concentrations determined. The average age of the patients at enrolment was 73.6 years.

For their analysis, Littlejohns and colleagues defined 25(OH)D concentrations of less than 25 nmol/L as severely deficient, 25-50 nmol/L as deficient, and greater than 50 nmol/L as sufficient.

All cause dementia and Alzheimer’s disease were diagnosed using criteria from the National Institute of Neurological and Communicative Disorders and Stroke, and the Alzheimer’s Disease and Related Disorders Association. The data were adjusted to account for such factors as smoking history, alcohol use, education and socioeconomic status, body mass index, and the time of year when serum was drawn.

The researchers reported that, after a mean follow-up of 5.6 years (standard deviation 1.6, median 6.1, range 0.1 to 8.4), 171 participants had developed all cause dementia and 102 had developed Alzheimer’s disease.

Compared with the participants who had sufficient 25(OH)D concentrations, the adjusted hazard ratio for all cause dementia was 2.25 (95% confidence interval 1.23 to 4.13) in participants who were severely deficient and 1.53 (1.06 to 2.21) in participants who were deficient. The hazard ratio for Alzheimer’s disease was 2.22 (1.02 to 4.83) in participants who were severely deficient and 1.69 (1.06 to 2.69) in those who were deficient.

How vitamin D might reduce the risk of dementia and Alzheimer’s disease is unknown, the researchers noted, but some vitamin D receptors are expressed in the brain, and the active form of the vitamin—1,25-dihydroxyvitamin D3—regulates neurotrophic factors involved in the survival, development, and function of neural cells.

In vitro, vitamin D stimulates macrophages, which increases the clearance of amyloid plaques, wrote the researchers, and the vitamin reduces amyloid induced cytotoxicity and apoptosis in primary cortical neurons. Vitamin D deficiencies have also been linked to cerebrovascular pathology that might increase the risk of stroke, they said.

The researchers concluded, “Our findings support the hypothesis that vitamin D may be neuroprotective and that “sufficiency” in the context of dementia risk may be in the region of 50 nmol/L.”

Simon Ridley, head of research at Alzheimer’s Research UK, who was not involved in the study, said that the research strengthened the evidence of an association between vitamin D levels and the risk of dementia but that it did not show that low vitamin D levels caused dementia.

“To be certain whether increasing vitamin D could help protect against dementia, we would need to see large scale clinical trials. Vitamin D is essential for keeping our bodies healthy, and although these results don’t suggest people should start dosing up on supplements, it’s important for people to ensure they are getting enough vitamin D,” said Ridley.

“Anyone who is considering changing their diet to include vitamin supplements should speak to a doctor,” he added.


Cite this as: BMJ 2014;349:g5049


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