Vitamin D, Homocysteine, and Folate in Subcortical Vascular Dementia and Alzheimer Dementia

Abstract

Dementia is a worldwide health problem which affects millions of patients; Alzheimer's disease (AD) and subcortical vascular dementia (sVAD) are the two most frequent forms of its presentation. As no definite therapeutic options have been discovered, different risk factors for cognitive impairment have been searched for potential therapies. This report focuses on the possible evidence that vitamin D deficiency and hyper-homocysteinemia can be considered as two important factors for the development or the progression of neurodegenerative or vascular pathologies. To this end, we assessed: the difference in vascular risk factors and vitamin D-OH25 levels among groups of sVAD, AD, and healthy age-matched controls; the association of folate, B12, homocysteine, and vitamin D with sVAD/AD and whether a deficiency of vitamin D and an increment in homocysteine levels may be related to neurodegenerative or vessel damages. The commonly-considered vascular risk factors were collected in 543 patients and compared with those obtained from a healthy old volunteer population. ANOVA group comparison showed that vitamin D deficiency was present in demented cases, as well as low levels of folate and high levels of homocysteine, more pronounced in sVAD cases. The statistical models we employed, with regression models built, and adjustments for biochemical, demographic and neuropsychiatric scores, confirmed the association between the three measures (folate decrease, hyperhomocysteinemia and vitamin D decrease) and dementia, more pronounced in sVAD than in AD.

The combined presence of hypertension and vitamin D deficiency increased the probability of the occurrence of small vessel disease in China

“…However, the above studies had a limited representation of individuals from China. In our study, we further confirmed patients with SVD were correlated with the deficiency of 25(OH)D. Our study was in line with the former studies from different races including in Nepal, India, Iran and Italy [15,[31][32][33][34][35][36][37].…”

Environmental UVR Levels and Skin Pigmentation Gene Variants Associated with Folate and Homocysteine Levels in an Elderly Cohort

“…This suggests homocysteine may be decreased by processes which are upregulated following UVR exposure. Vitamin D, which is consistently inversely associated with homocysteine levels [50][51][52][53][54], may be involved in this process or may be a marker of sun-exposure, supporting this hypothesis. Increased oxidative stress following UVR exposure may also influence homocysteine levels, by promoting homocysteine auto-oxidization and the formation of homocysteine into another oxidant not detected by homocysteine assays [55].…”

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

“…Interestingly, the highest level significantly correlated with all causes of dementia, and especially of VaD, even after adjusting for age, gender, apolipoprotein E4 (APOE4), education, body mass index, MMSE, hypertension, cerebrovascular events, and estimated glomerular filtration rate [52]. These results were confirmed by Moretti and colleagues, who found a higher homocysteine level in VaD patients, but also a significantly vitamin D deficiency and low levels of folate [16], as well as in elderly patients with fatigue [56]. Liu and co-workers suggested a biomarker panel of three metabolites (glutamine, kynurenine, and lysophosphatidylcholines) to predict the post-stroke cognitive impairment [12].…”

“…Therefore, a total of 46 papers were eventually included in this study ( Figure 1) and the main findings are summarized in Table 1. More in details, 8 studies deal with serum biomarkers [9][10][11][12][13][14][15][16], 10 with cerebrospinal fluid (CSF) [17][18][19][20][21][22][23][24][25][26], 4 with neuroimaging [27][28][29][30], 6 with histopathology [31][32][33][34][35][36], and 14 with transcranial magnetic stimulation (TMS) [37][38][39][40][41][42][43][44][45][46][47][48][49][50]; 4 studies included more than one technique: one studied both serum and CSF markers [51], two both serum and neuroimaging [52,53], and one both CSF and neuroimaging…”

“…Some studies have identified serological markers that can support the diagnosis of VaD. For instance, pro-inflammatory metabolites (such as NO-related molecules), cytokines (including IL-1β, TNF-α, IFN-γ, IL-4, IL-5, IL-8, G-CSF, and MIP-1b), and markers of endothelial dysfunction (e.g., homocysteine) were found to be increased in VaD patients [11,16,[51][52][53]. Furthermore, an altered systemic redox balance was demonstrated in VCI, in which reduced antioxidant enzymes, such as the activity of arylesterase and paraoxonase, were associated with the risk of developing dementia [13,14].…”