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Recent study reviews whether current research on vitamin D and dementia follows Hill’s criteria for causation

Posted on: May 9, 2016   by  John Cannell, MD


Professor Cedric Annweiller of the Angers University Hospital in France recently wrote a review paper on vitamin D and dementia to see if the current evidence meets Hill’s criteria for causation. To view an image comparing a healthy brain to to one with advanced alzheimer’s, click here.

Annweiler C. Vitamin D in dementia prevention. Ann N Y Acad Sci. 2016 Mar;1367(1):57-63. 

Most of you likely remember the remarkable JAMA-Neurology paper that found those with the lowest vitamin D levels were three times more likely to develop dementia.

Low vitamin D status may increase risk of dementia

This paper along with others led Dr. Annweiller to investigate whether the evidence to date is strong enough to satisfy Hill’s criteria, which is a collection of findings seen when causation is likely. Here is what he found:

  • Temporality: Vitamin D deficiency precedes the onset of cognitive decline in cohort studies.
  • Strength of association: Low vitamin D is associated with cognitive disorders, with an odds ratio of greater than 2; meaning that the risk of cognitive disorders is more than twice as high in the case of low vitamin D.
  • Dose–response relationship: In most previous studies, higher 25OHD concentration was associated with better cognitive performance and decreased risk of dementia.
  • Consistency of findings: Significant observational evidence is available from cross-sectional and longitudinal studies, but interventional evidence is limited.
  • Plausibility: Vitamin D is involved in neurophysiology and neuroprotection of the brain.
  • Alternate explanations: Reverse causation (i.e., dementia precipitates hypovitaminosis D) is unlikely, because cohort studies show low vitamin D precedes dementia. Also, association between low vitamin D and dementia remains significant after adjustment for all potential confounders.
  • Experiments: Limited studies show cognitive improvements after vitamin D supplementation in the dementia and older patients.
  • Specificity: This criteria was not met. Although low vitamin D is very common among individuals with dementia, the prevalence of low D is too high in the general older population to be considered specific to dementia.
  • Coherence with known facts: Robust evidence exists that serum vitamin D status is a biological determinant associated with cognitive function in older adults.

He concluded:

“The correction of hypovitaminosis D in older adults is justified from a cognitive perspective in preclinical studies and by a number of cross-sectional and longitudinal observational studies reporting direct associations between decreased 25OHD concentrations and cognitive disorders.”

It is important to remember that you can get dementia with a high 25(OH)D status as well. Maintaining a healthy D level simply reduces the risk of developing the disease.

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