Vitamin D, Cognition and Alzheimer’s Disease: The Therapeutic Benefit is in the D-Tails

2016
Véréna Landel, Cédric Annweiler, Pascal Millet, Maria Morello, and François Féron

Abstract

Since its discovery during the epidemic of rickets in the early 1920s, the physiological effects of vitamin D on calcium/phosphorus homeostasis have been thoroughly studied. Along with the understanding of its actions on skeletal diseases and advances in cellular and molecular biology, this misnamed vitamin has gained attention as a potential player in a growing number of physiological processes and a variety of diseases. During the last 25 years, vitamin D has emerged as a serious candidate in nervous system development and function and a therapeutic tool in a number of neurological pathologies. More recently, experimental and pre-clinical data suggest a link between vitamin D status and cognitive function. Human studies strongly support a correlation between low levels of circulating 25-hydroxyvitamin D (25(OH)D) and cognitive impairment or dementia in aging populations. In parallel, animal studies show that supplementation with vitamin D is protective against biological processes associated with Alzheimer’s disease (AD) and enhances learning and memory performance in various animal models of aging and AD. These experimental observations support multiple mechanisms by which vitamin D can act against neurodegenerative processes. However, clinical interventional studies are disappointing and fail to associate increased 25(OH)D levels with improved cognitive outcomes. This review collects the current available data from both animal and human studies and discusses the considerations that future studies examining the effects of vitamin D status on neurocognitive function might consider.

CONCLUSION

Vitamin D, produced by the skin under UV stimulation or ingested from food, is now described as a steroid hormone, essential for human health. More recently, accumulating evidence indicate that this hormone is a neurosteroid that may be important in aging and age-related cognitive decline. More precisely, numerous preclinical and clinical studies suggest that hypovitaminosis D may be associated with increased risk of developing AD and dementia, without being a causal agent. Inducing genomic and non genomic effects, vitamin D plays a role on calcium homeostasis, neurotransmission, vascularization, Aβ and Tau accumulation, oxidative stress, and inflammation, all of which are disturbed in AD. However, vitamin D’s pleiotropic action is cell-, tissue-, time-, individual-, dose-, pathological context- and, maybe, gender-dependent. As a result, in view of personalized medicine, future randomized trials should take into account the D-tails of every individual included in the cohorts.