Robert HHowland, Associate Professor of Psychiatry, University of Pittsburgh Medical Centerhowlandrh@upmc.edu
Submitted August 28, 2014
In their post-hoc analysis of data from a prospective cohort study originally designed to investigate causes of cardiovascular disease, Littlejohns et al. [1] found baseline vitamin D deficiency was associated with a subsequent increased incidence of all-cause dementia, consistent with other observational association studies. Holick [2] described vitamin D deficiency as pandemic, affecting an estimated one billion or more people worldwide. Results from seven population based studies suggest the prevalence and incidence of dementia might be decreasing, [3,4] including in England [4] where rates of rickets have steadily increased during the past two decades. [5] If there is a valid association between vitamin D deficiency and dementia, why are declining rates of dementia seen amidst a vitamin D deficiency pandemic?
Although preclinical studies provide a plausible mechanism linking vitamin D deficiency to cognitive impairment, causality cannot be established from association studies. Statistically significant but weak associations in observational studies are likely to be false and attributable to various sources of bias.
Large observational studies, or meta-analyses of observational studies, enable greater precision and statistical significance of a finding, but this does not eliminate bias or provide validation.
1. Littlejohns TJ, Henley WE, Lang IA, et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology Epub 2014 Aug 6.
2. Holick MF. The vitamin D deficiency pandemic: A forgotten hormone important for health. Public Health Rev 2010;32:267-283.
3. Larson EB, Yaffe K, Langa KM. New insights into the dementia epidemic. N Engl J Med 2013;369:2275-2277.
4. Matthews FE, Arthur A, Barnes LE, et al. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: Results of the Cognitive Function and Ageing Study I and II. Lancet 2013;382:1405-1412.
5. Goldacre M, Hall N, Yeates DGR. Hospitalisation for children with rickets in England: A historical perspective. Lancet 2014;383:597-598.
In their post-hoc analysis of data from a prospective cohort study originally designed to investigate causes of cardiovascular disease, Littlejohns et al. [1] found baseline vitamin D deficiency was associated with a subsequent increased incidence of all-cause dementia, consistent with other observational association studies. Holick [2] described vitamin D deficiency as pandemic, affecting an estimated one billion or more people worldwide. Results from seven population based studies suggest the prevalence and incidence of dementia might be decreasing, [3,4] including in England [4] where rates of rickets have steadily increased during the past two decades. [5] If there is a valid association between vitamin D deficiency and dementia, why are declining rates of dementia seen amidst a vitamin D deficiency pandemic? Although preclinical studies provide a plausible mechanism linking vitamin D deficiency to cognitive impairment, causality cannot be established from association studies. Statistically significant but weak associations in observational studies are likely to be false and attributable to various sources of bias. Large observational studies, or meta-analyses of observational studies, enable greater precision and statistical significance of a finding, but this does not eliminate bias or provide validation.
1. Littlejohns TJ, Henley WE, Lang IA, et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology Epub 2014 Aug 6.
2. Holick MF. The vitamin D deficiency pandemic: A forgotten hormone important for health. Public Health Rev 2010;32:267-283.
3. Larson EB, Yaffe K, Langa KM. New insights into the dementia epidemic. N Engl J Med 2013;369:2275-2277.
4. Matthews FE, Arthur A, Barnes LE, et al. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: Results of the Cognitive Function and Ageing Study I and II. Lancet 2013;382:1405-1412.
5. Goldacre M, Hall N, Yeates DGR. Hospitalisation for children with rickets in England: A historical perspective. Lancet 2014;383:597-598.
For disclosures, contact journal@neurology.org.