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.
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.
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.
“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.