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Low Vitamin D Levels Associated With Cognitive Decline

Older adults with low levels of vitamin D appear more likely to experience declines in thinking, learning and memory over a six-year period, according to a report in the July 12, 2010 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

An estimated 40 percent to 100 percent of older adults in the United States and Europe are deficient in vitamin D, according to background information in the article. This deficiency has been linked to fractures, various chronic diseases and death. Vitamin D may help prevent the degeneration of brain tissue by having a role in formation of nervous tissue, maintaining levels of calcium in the body, or clearing of beta-amyloid, the substance that forms the brain plaques and tangles associated with Alzheimer’s disease.

David J. Llewellyn, Ph.D., of University of Exeter, England, and colleagues assessed blood levels of vitamin D in 858 adults who were age 65 or older when the study began in 1998. Participants completed interviews and medical examinations and provided blood samples. At the beginning of the study and again after three and six years, they repeated three tests of cognitive function—one assessing overall cognition, one focusing on attention and one that places greater emphasis on executive function, or the ability to plan, organize and prioritize.

Participants who were severely deficient in vitamin D (having blood levels of 25-hydroxyvitamin D less than 25 nanomoles per liter) were 60 percent more likely to have substantial cognitive decline in general over the six-year period and 31 percent more likely to experience declines on the test measuring executive function than those with sufficient vitamin D levels. “The association remained significant after adjustment for a wide range of potential confounders and when analyses were restricted to elderly subjects who were non-demented at baseline,” the authors write. However, no significant association was seen for the test measuring attention.

“If future prospective studies and randomized controlled trials confirm that vitamin D deficiency is causally related to cognitive decline, then this would open up important new possibilities for treatment and prevention,” the authors conclude.

Editorial: Randomized Controlled Trials Needed to Examine Vitamin D’s Role

“Vitamin D has been known for many years to play a critical role in skeletal health, such that very low levels of this hormone (less than 20 nanomoles per liter) can cause osteomalacia, a disorder of impaired bone mineralization,” write Andrew Grey, M.D., and Mark Bolland, M.B.Ch.B., Ph.D., of University of Auckland, New Zealand, in an accompanying editorial. “More recently, observational studies have reported inverse associations between levels of serum 25-hydroxyvitamin D, the metabolite that best reflects overall vitamin D status, and the risk of a wide range of disease, including cancer, vascular disease, infectious conditions, autoimmune diseases, osteoporosis, type 2 diabetes mellitus and obesity.”

“The results of these observational studies have prompted calls for widespread treatment of individuals with low levels of vitamin D and the establishment of public health programs aimed at raising the population levels of vitamin D to ‘healthy’ values,” the authors write.

“It is now time to test the various hypotheses generated by observational studies of vitamin D, including that of Llewellyn et al, in adequately designed and conducted randomized controlled trials,” they conclude. “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. We should invest in trials that provide the best possible evidence on the benefits and risks of vitamin D before we invest in costly, difficult and potentially unrewarding interventional strategies.”

Abstract

BACKGROUND: To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia. METHODS: We determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population-based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. RESULTS: The multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25(OH)D deficient (levels <25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (>/=75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A. CONCLUSION: Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.

Source

Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, Ferrucci L, Melzer D. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med. 2010 Jul 12;170(13):1135-41. PMID: 20625021

Arch Intern Med. 2010;170[13]:1099-1100.

American Medical Association (AMA) July 12, 2010

Key concepts: Vitamin D, cognitive decline, memory