Abstract

In 1983, Goodwin et al.1 published a seminal article in which they evaluated cross-sectional associations between cognitive function test scores and blood levels of micronutrients in noninstitutionalized, healthy older adults (age >60 y). They found that low blood concentrations of vitamin C, vitamin B12, riboflavin, and folate were associated with poor performance on tests of nonverbal abstract thinking or short-term memory. This was the first epidemiologic evaluation of subclinical micronutrient deficiency and its potential to influence cognitive function in otherwise healthy older adults. In the ensuing 25+ years, hundreds of reports have linked micronutrients to both global and domain-specific cognitive functions, as well as risk of dementia and Alzheimer disease. The current “hot” vitamin receiving attention is vitamin D, and not simply because it is made in the skin upon exposure to sunlight. Well-recognized for its role in preventing rickets in children and osteomalacia in adults, there is increasing evidence that vitamin D influences a variety of pathophysiologic conditions, including age-related cognitive dysfunction and dementia.2–4 The vitamin D receptor and the vitamin D activating enzyme, 1,α-hydroxylase, are expressed throughout the brain,2–4 and vitamin D is known to affect the expression of various neurotrophins and calcium binding proteins that are essential for normal brain function.2–4 Vitamin D also stimulates neurite outgrowth in human neuroblastoma cells and in rodent embryonic hippocampal explants and progenitor cell lines, and increases hippocampal density in rats.2 Deficiency of vitamin D in rodents increases ventricle size and alters learning and other behavioral parameters.2 There is also evidence …

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