ARTICLE IN BRIEF
Two independent research groups showed a connection between vitamin D deficiency and cognitive decline in cross-sectional studies, while the third found no statistically significant association in a longitudinal study.
While vitamin D has long been known to assist calcium absorption in the body, investigators have begun to explore, as well, its role in supporting cognitive function and preventing dementia.
But exactly what that role is requires further research, according to the lead investigators of three studies published online Nov. 25 ahead of the Jan. 5 print edition of Neurology. Two independent research groups showed a connection between vitamin D deficiency and cognitive decline in cross-sectional studies, while the third found no statistically significant association in a longitudinal study.
Although the findings were inconclusive, the investigators agreed on this point: Clinicians need to be careful in prescribing supplements, because it is unclear what dose, if any, is most effective. And they warned patients not to consider vitamin D a “wonder drug,” because, unlike vitamin C excess, which the body eliminates, vitamin D is stored in fat, and an overdose can cause problems.
In one study, led by Katherine Tucker, PhD, professor of nutritional epidemiology who has since moved from Tufts to Northeastern University,
Investigators used MRI to evaluate the association of vitamin D with dementia and stroke in 318 elderly people receiving home health care.
Researchers used MRI to measure total intracranial volume, total brain volume, and CSF volume as well as brain lesions. Using that analysis, neurologists then diagnosed various stages of cognitive decline, including Alzheimer disease and dementia. They also took blood samples to assess the levels of vitamin D.
Fifteen percent of the group was deemed vitamin D deficient, meaning that they had less than 10 ngml. Another 44.3 percent were assessed to be vitamin D insufficient, with between 10 and 20 ng/ml blood analysis. The group as a whole had a mean score of 19.9 nm/ml.
Nearly 24 percent of the study group had dementia. Those with dementia had lower blood levels of vitamin D — 16.8 ng/ml.
After adjusting for age, race, body mass index, gender, and education, vitamin D deficiency was associated with more than twice the odds of Alzheimer disease (AD), other causes of dementia, and stroke.
The findings suggest a potential vasculoprotective role of vitamin D, Dr. Tucker said. It is unclear how the vitamin could play a role in protecting the brain, she said. But, she added, vitamin D receptor and the vitamin D activating enzyme, 1,alpha-hydroxylase, occur throughout the brain and not only product calcium binding proteins and there is evidence that vitamin D suppresses inflammation, possibly preventing neurodegeneration.
In another study, Cedric Annweiler, MD and colleagues in the department of Geriatrics at Angers University Hospital in France, assessed cognitive function using Pfeiffer's Short Portable Mental State Questionnaire in 725 community-living women over the age of 75, 17 percent of whom had vitamin D deficiency. Those with vitamin D deficiency had a lower mean score as well as a higher risk for cognitive impairment, assessed by using Pfeiffer's Short Portable Mental State Questionnaire.
“Exactly how vitamin D and cognition are associated and if this association is causal remains unclear,” the investigators wrote.
Low cognitive function could lead to low dietary intake of vitamin D or a lack of sunlight exposure, which in turn could lead to low vitamin D serum concentrations, the investigators speculated. However, they noted that the study population was relatively healthy, and physically active. The association between serum vitamin D deficiency and cognitive impairment remained significant even after adjustment for these covariables.
However, Dr. Annweiler said researchers should consider that it might not be the lack of vitamin D that caused the cognitive decline, but that those with dementia and other neurodegenerative diseases might live lives that lead to the lack of vitamin D.
The third study, led by Yelena Slinin, MD, MS, a nephrologist at the University of Minnesota School of Medicine and an assistant professor in internal medicine, did not find a statistically significant association between Vitamin D and cognitive decline, however. The investigators followed 1,604 men over the age of 65 who were enrolled in the Osteoporotic Fractures in Men study. They followed them for an average of 4.6 years.
The investigators measured levels of vitamin D and assessed cognitive function using the Modified Mini-Mental State Examination and other tests that assess visual conceptual and visuomotor tracking.
The men in her study were healthy and living in communities and about 25 percent of the participants had severe vitamin D deficiency.
“Our study did not support the use of routine vitamin D for cognitive decline,” but, she cautioned, it was an observational study. “At this point, other studies are needed.”
MORE RESEARCH NEEDED
Commenting on the papers, Martha Payne, PhD, MPH, RD, co-director of the Neuropsychiatry Imaging Release Laboratory at Duke University Medical Center, said the three studies were a good start but more research is needed. “There is not enough information yet to give guidance to clinicians,” said Dr. Payne.
In a 2008 paper in Nutritional Research, Dr. Payne had reported an association between higher levels of vitamin D and increased brain lesions. She contends that because vitamin D is implicated with calcium metabolism, that higher levels could lead to arterial calcification.
Dr. Payne noted that “there are significant differences between the studies, including differences in sample sections and covariates. And a lot of factors such as changes in diet or physical activity may have led to low vitamin D and other factors, such as depression, may have also contributed to cognitive impairment,” she said.
Dr. Payne is focusing her next study on brain lesions, calcium, and vitamin D, and how these relationships may be mediated by depression.
“Depressed individuals might eat differently and not take in enough vitamins which could lead to cognitive impairment. There might be a more holistic approach assessed by a longitudinal study.”