25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services
CédricAnnweiler, Angers University Hospital,, 49933 Angers, Cedex 9, Franceceannweiler@chu-angers.fr
Didier Le Gall, Bruno Fantino, and Olivier Beauchet.
Submitted March 08, 2010
In this cross-sectional study, Buell et al. showed that 25OHD ≤ 20ng/mL indicated a 2.2-fold risk for all-cause dementia, a 2.7-fold risk for Alzheimer disease (AD), and a 2.3-fold risk for stroke. [1] These results remained significant even after adjustment for a list of covariates.
However, adjusting for all potential confounders is essential to determine if the association is really significant or explained by confounders. [2] Confounder “C” is defined by two conditions: a covariate significantly associated with both the outcomes “Y” and “X”; and the association of “X” with “Y” vanished when adjusting for both “C” and “X”. [2] In addition, “C” remains a confounder even when it is not statistically significant by itself because it changes the effect of the exposure of “Y” to “X” when it is included in the model, or because it is a confounder only when included with other covariates. [2] This point is particularly important since vitamin D belongs to a complex biological system.
First, 25OHD insufficiency causes an elevation of serum parathyroid hormone (PTH). [3] This inverse correlation does not answer whether 25OHD insufficiency itself or secondary hyperparathyroidism acts on brain tissue. The association of elevated serum PTH with cognition has been reported in patients with primary hyperparathyroidism whose clinical features include dementia, which could be reversed after parathyroidectomy. [4] In the Helsinki Aging Study, high PTH concentrations also indicated an independent two-fold risk for a five-year cognitive decline. [3] Due to the difficulties of interpretation of any separate effects, PTH should be considered a potential confounder while investigating vitamin D and cognition.
In addition, vitamin D regulates the absorption and flow of calcium, which has also been associated with dementia. The elevation of intracellular calcium leads to neuronal cell death. [5] Schram et al. found that high serum calcium concentrations were associated with worse global cognitive function at baseline and a faster cognitive decline over age 75. [5]
Future investigations are necessary to adjust for the covariates of PTH and calcium while exploring the association between variable 25OHD and dementia.
References
1. Buell JS, Dawson-Hughes B, Scott TM, et al. 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 2010; 74: 18-26.
2. Greenland S, Pearl J, Robins JM. Causal diagrams for epidemiologic research. Epidemiology 1999;10:37-48.
3. Björkman MP, Sorva AJ, Tilvis RS. Does elevated parathyroid hormone concentration predict cognitive decline in older people? Aging Clin Exp Res Epub 2009 Nov 17.
4. Formiga F, Mascaró J, Chivite D, Pujol R. Reversible dementia due to two coexisting diseases. Lancet 2000;355:1154.
5. Schram MT, Trompet S, Kamper AM, et al. Serum calcium and cognitive function in old age. J Am Geriatr Soc 2007;55:1786-1792.
Disclosure: Dr. Annweiler serves as a consultant for Ipsen Pharma. Prof. Beauchet serves as a consultant for Ipsen Pharma; serves on a scientific advisory board for Groupe Korian; and serves as an editor for Annales de Gérontologie. Prof. Le Gall and Fantino report no disclosures.
In this cross-sectional study, Buell et al. showed that 25OHD ≤ 20ng/mL indicated a 2.2-fold risk for all-cause dementia, a 2.7-fold risk for Alzheimer disease (AD), and a 2.3-fold risk for stroke. [1] These results remained significant even after adjustment for a list of covariates.
However, adjusting for all potential confounders is essential to determine if the association is really significant or explained by confounders. [2] Confounder “C” is defined by two conditions: a covariate significantly associated with both the outcomes “Y” and “X”; and the association of “X” with “Y” vanished when adjusting for both “C” and “X”. [2] In addition, “C” remains a confounder even when it is not statistically significant by itself because it changes the effect of the exposure of “Y” to “X” when it is included in the model, or because it is a confounder only when included with other covariates. [2] This point is particularly important since vitamin D belongs to a complex biological system.
First, 25OHD insufficiency causes an elevation of serum parathyroid hormone (PTH). [3] This inverse correlation does not answer whether 25OHD insufficiency itself or secondary hyperparathyroidism acts on brain tissue. The association of elevated serum PTH with cognition has been reported in patients with primary hyperparathyroidism whose clinical features include dementia, which could be reversed after parathyroidectomy. [4] In the Helsinki Aging Study, high PTH concentrations also indicated an independent two-fold risk for a five-year cognitive decline. [3] Due to the difficulties of interpretation of any separate effects, PTH should be considered a potential confounder while investigating vitamin D and cognition.
In addition, vitamin D regulates the absorption and flow of calcium, which has also been associated with dementia. The elevation of intracellular calcium leads to neuronal cell death. [5] Schram et al. found that high serum calcium concentrations were associated with worse global cognitive function at baseline and a faster cognitive decline over age 75. [5]
Future investigations are necessary to adjust for the covariates of PTH and calcium while exploring the association between variable 25OHD and dementia.
References
1. Buell JS, Dawson-Hughes B, Scott TM, et al. 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 2010; 74: 18-26.
2. Greenland S, Pearl J, Robins JM. Causal diagrams for epidemiologic research. Epidemiology 1999;10:37-48.
3. Björkman MP, Sorva AJ, Tilvis RS. Does elevated parathyroid hormone concentration predict cognitive decline in older people? Aging Clin Exp Res Epub 2009 Nov 17.
4. Formiga F, Mascaró J, Chivite D, Pujol R. Reversible dementia due to two coexisting diseases. Lancet 2000;355:1154.
5. Schram MT, Trompet S, Kamper AM, et al. Serum calcium and cognitive function in old age. J Am Geriatr Soc 2007;55:1786-1792.
Disclosure: Dr. Annweiler serves as a consultant for Ipsen Pharma. Prof. Beauchet serves as a consultant for Ipsen Pharma; serves on a scientific advisory board for Groupe Korian; and serves as an editor for Annales de Gérontologie. Prof. Le Gall and Fantino report no disclosures.