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

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.

Serum vitamin D in patients with mild cognitive impairment and Alzheimer's disease

“…Vitamin D decreases the burden of major pathological aggregates in AD, including Aβ plaques and hyperphosphorylated tau protein (Durk, Han, & Chow, 2014;Yu et al, 2011) and augments activity of memantine in AD (Lemire, Brangier, Beaudenon, Duval, & Annweiler, 2016). Moreover, many reports suggest a relationship between vitamin D deficiency with MCI (Annweiler et al, 2012;Yin, Fan, Lin, Xu, & Zhang, 2015) and AD (Annweiler et al, 2010(Annweiler et al, , 2011Landel, Annweiler, Millet, Morello, & Féron, 2016;Nissou et al, 2014;Schlögl & Holick, 2014).…”

Crosstalk between sphingolipids and vitamin D3: potential role in the nervous system

“…For example, 1,25(OH) 2 D 3 may regulate the expression of many genes associated with AD and attenuate the build up of Aβ deposits either by enhancing their clearance (transport to the blood or to the CSF) or by stimulating the phagocytosis of Aβ. It is likely that the hormone alters APP processing and prevents the defects in ACh by increasing the activity of choline acetyltransferase (thus ACh synthesis) in the brain (Briones and Darwish, ; Annweiler et al, ; Durk et al, ; Landel et al, ).…”

Reduction of Cognitive Decline in Patients with or at High Risk for Diabetes

“…However, clinical interventional studies have failed to show that supplementation with Vitamin D improves cognitive outcomes in individuals [48]. The purposes of the clinical trial NCT02416193 were to determine (1) the effect of vitamin D3 supplementation on cognitive function and (2) the effect of vitamin D3 supplementation on diabetes self-management in participants with type 2 diabetes who have symptoms of cognitive impairment but are not demented.…”