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Is Vitamin D Important in the Prevention of Dementia?
Abstract & Commentary
By Michael Lin, MD, Associate Professor of Neurology and Neuroscience, Weill Cornell Medical College. Dr. Lin reports no financial relationships relevant to this field of study. This article originally appeared in the March issue of Neurology Alert. At that time it was peer reviewed by M. Flint Beal, MD, Anne Parrish Titzel Professor, Department of Neurology and Neuroscience, Weill Cornell Medical Center, New York, NY. Dr. Beal reports no financial relationship to this field of study.
Synopsis: Severe Vitamin D deficiency appears to worsen dementia and supplementation may be beneficial.
Sources: Llewellyn DJ, Lang IA, Langa KM, et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med 2010;170:1135-1141. Evatt ML. Vitamin D and cognitive decline in elderly persons: Further details. Arch Neurol 2010;67:1513-1515.
Vitamin D recently has been associated with a range of conditions other than osteopenia, including neurologic diseases such as multiple sclerosis. There is also reason to suspect that vitamin D may play a role in cognitive decline. Several previous cross-sectional studies have found an association between vitamin D and cognition in elderly subjects, although this finding has not been consistent. Llewellyn and colleagues have now published the first prospective study examining vitamin D and cognition in elderly subjects, and found that low vitamin D levels were associated with increased risk of substantial cognitive decline.
The authors examined adults 65 years or older enrolled in the InCHIANTI study, a prospective population-based cohort study conducted in Tuscany between 1998 and 2006, with follow-up assessments every 3 years. A total of 858 subjects consented and completed blood draws and at least one follow-up assessment, with a mean (± SD) follow-up of 5.2 ± 1.3 years. The study measured 25-hydroxyvitamin D (25(OH)D) levels, and cognition assessed using the Mini-Mental State Exam (MMSE) and Trail Making Tests A and B. Substantial decline was defined as a drop of 3 or more points on the MMSE, or the worst 10% of the distribution of decline on the Trail Making Tests, or discontinuation due to excessive mistakes.
The relative risk of substantial decline on the MMSE in subjects with severe vitamin D deficiency (25(OH)D < 25 nM) compared to subjects with sufficient vitamin D levels (25(OH)D > 75 nM) was 1.60 (95% confidence interval [CI] 1.19-2.00). For the same groups, the relative risk of substantial decline on Trails B was 1.31 (95% CI 1.03-1.51). For both the MMSE and Trails B, the P values for a linear trend were statistically significant, suggesting a dose-response relationship. No association was seen for Trails A. All associations remained significant after extensive adjustment for confounding factors that might affect cognition or vitamin D levels (age, sex, education, baseline cognitive score, season tested, smoking, depression, body mass index, alcohol consumption, caloric intake, vitamin E level, mobility) or factors that might potentially mediate an association between vitamin D and neurologic status (stroke, diabetes, hypertension).
This study has a number of strengths. It is the first prospective study of vitamin D and cognition in elderly subjects, with straightforward design and well-recognized endpoints. It was large, and the investigators were able to adjust for a wide range of confounding variables. In particular, it is unlikely that the observed association was due to reverse causation; i.e., that baseline dementia or impaired mobility reduced vitamin D levels by affecting diet or exposure to sunlight. On the other hand, the study was geographically confined, and all participants were of white European origin. Replication in other locales and populations is necessary. Moreover, the specific causes of cognitive decline were not assessed.
The authors review a number of biologic studies implicating vitamin D in neurologic function and supporting its potential involvement in neurodegeneration. Neurons and glia express vitamin D receptors and enzymes involved in vitamin D metabolism. Vitamin D affects neuronal calcium levels, reduces oxidative stress by inhibiting inducible nitric oxide synthase and increasing glutathione levels, and regulates the synthesis of neurotrophic factors and stimulates neurogenesis. Vitamin D is an immunosuppressor and may reduce autoimmune damage. Vitamin D also stimulates Aβ phagocytosis and clearance by macrophages, and protects against apoptosis. On the other hand, caution is necessary, as excessive vitamin D intake has a number of adverse effects, including renal toxicity and potentially pancreatic cancer.