EXETER, England—Older adults with lower blood levels of vitamin D appear at higher risk for substantial cognitive decline, according to a new study out of the University of Exeter (Arch Intern Med. 12 July 2010;170(13):1135-41). David J. Llewellyn, Ph.D., and colleagues noted between 40 and 100 percent of older adults in the United States and Europe are deficient in vitamin D, and that deficiency has been linked to an increased incidence of various chronic diseases.
In the current study, the research team examined blood serum levels of 25-hydroxyvitamin D (25[OH]D, a marker of vitamin D status) and risk of substantial cognitive decline in the InCHIANTI population-based study, conducted in Tuscany, Italy, between 1998 and 2006. Data for 858 adults aged 65 or older at the start of the study included blood samples and results of several cognitive tests, including the Mini-Mental State Examination (MMSE) and Trail-Making Tests A and B. Substantial decline in cognition was defined as a loss of 3 or more points on the MMSE during a six-year period and/or the worst 10 percent of distribution of decline on the Trail-Making Tests.
Subjects with the lowest levels of 25(OH)D (<25 nmol/L) had a 60 percent increased chance of having substantial cognitive decline compared to those with sufficient (≥75 nmol/L) levels; those adults with the lowest levels were also 31 percent more likely to have declines on the test measuring executive function. The association remained significant after adjusting for several confounders and when the analysis was restricted to elderly subjects who were non-demented at baseline.
The researchers noted the results echo those of several previous population-based, cross-sectional studies that also found significant associations between low levels of plasma vitamin D and cognitive dysfunction, particularly executive function and attention. They concluded, “If future prospective studies and randomized controlled trials [RCTs] confirm that vitamin D deficiency is causally related to cognitive decline, then this would open up important new possibilities for treatment and prevention.”
An accompanying editorial in the issue (170(13):1099-1100) acknowledged the increasing quantity of observational data linking deficiencies in vitamin D to increased risk for several diseases including cancer, vascular disease, osteoporosis, type 2 diabetes and, now, accelerated cognitive decline. However, Andrew Grey, M.D., and Mark Bolland, Ph.D., from the University of Auckland, New Zealand, questioned whether establishing programs to raise populations’ levels of vitamin D are needed at this time. Instead, they state, “It is now time to test the various hypotheses generated by observational studies of vitamin D … in adequately designed and conducted RCTs. … Very importantly, such trials will also provide an opportunity to systematically assess potential harms of vitamin D supplementation, an issue that has been largely overlooked or dismissed.”
Andrew Shao, Ph.D., senior vice president, scientific and regulatory affairs, Council for Responsible Nutrition (CRN), agreed it is important to design and execute RCTs that support the findings of observational studies like Llewellyn’s. However, he said, “That doesn’t mean you can’t make recommendations based off of those studies. I would disagree with the tone of the editorial and focus on the fact that the next step is to use RCTs to better refine the proper dosage and appropriate population for the effect on cognitive decline.” Shao added the positive results of the Llewellyn study were consistent with the optimal/sufficient levels of vitamin D seen in other intervention and observational studies, concluding, “With most of the population having low vitamin D status, and so many established health effects, there is a need to improve people’s vitamin D status.”
