vitamin-d-2 and Alzheimer-Disease

Poor vitamin D nutrition is linked with dementia, but vitamin D has not been tested in a randomized controlled trial (RCT) in Alzheimer's disease (AD). Nasal insulin acutely improves cognition and vitamin D upregulates insulin receptor expression and enhances insulin action. In an RCT we examined the effect of high-dose vitamin D followed by nasal insulin on memory and disability in mild-moderate AD. 63 community-dwelling individuals aged > 60 were recruited; 32 with mild-moderate disease (Folstein Mini-Mental State Examination [MMSE] score 12-24) met entry criteria and were randomized. All took low-dose vitamin D (1000 IU/day) throughout. After run-in (8 weeks), they were randomized to additional high-dose D/placebo for 8 weeks, followed immediately by randomization to nasal insulin (60 IU qid)/placebo for 48 h. Primary outcome measures were Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and Disability Assessment in Dementia (after high-dose D) and ADAS-cog and Wechsler Memory Scale-Revised Logical memory (WMS-R LM) for immediate and delayed recall (after nasal insulin). Baseline median (interquartile range, IR) age, MMSE, and ADAS-cog were 77.5 (69-80), 19.5 (17-22), and 25.5 (20-31), respectively. Median 25OHD increased from 49 to 60 nM (p < 0.01) after run-in and was 187 nM after high-dose vitamin D and 72 nM after placebo (p < 0.001). Neither cognition nor disability changed significantly after high-dose D. ADAS-cog improved by a median (IR) of 9 (1-11) with nasal insulin after placebo high-dose vitamin D (p = 0.02), but may represent regression to the mean as WLS-R LM did not change. We conclude that high-dose vitamin D provides no benefit for cognition or disability over low-dose vitamin D in mild-moderate AD.

Topics: Administration, Intranasal; Aged, 80 and over; Alzheimer Disease; Cognition; Depression; Dietary Supplements; Double-Blind Method; Ergocalciferols; Feasibility Studies; Female; Humans; Hypoglycemic Agents; Insulin; Linear Models; Male; Middle Aged; Neuropsychological Tests; Pilot Projects; Treatment Outcome; Vitamin D Deficiency; Vitamins; Wechsler Scales

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).\ \ This article has been retracted at the request of the Corresponding Author, Yoshihiro Sato, and the co-authors have been informed.\ \ Dr. Sato wishes to retract this article on the grounds that it contains fabricated clinical trial data, which he was responsible for producing. In addition, Dr. Sato claims he listed all of the named co-authors without their consent. The co-authors were therefore unaware of the presence of fabricated data in this publication and their participation in the publication. This retraction was initiated by Dr. Sato, and the Editor-in-Chief of Bone was informed by the author directly.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Bone Density; Calcium; Ergocalciferols; Female; Fractures, Bone; Humans; Vitamin K 2

Recent studies have revealed that vitamin D deficiency may increase the risk of Alzheimer's disease, and vitamin D supplementation may be effective strategy to ameliorate the neurodegenerative process in Alzheimer's disease patients. Paricalcitol (PAL), a low-calcemic vitamin D receptor agonist, is clinically used to treat secondary hyperparathyroidism. However, the potential application of PAL for treating neurodegenerative disorders remains unexplored.. The APP/PS1 mice were intraperitoneally injected with PAL or vehicle every other day for 15 weeks. The β-amyloid (Aβ) production was confirmed using immunostaining and enzyme linked immunosorbent assay. The underlying mechanism was verified by western blot and immunostaining in vivo and in vitro.. Long-term PAL treatment clearly reduced β-amyloid (Aβ) generation and neuronal loss in APP/PS1 transgenic mouse brains. PAL stimulated the expression of low-density lipoprotein receptor-related protein 1 (LRP1) possibly through inhibiting sterol regulatory element binding protein-2 (SREBP2); PAL also promoted LRP1-mediated β-site APP cleavage enzyme 1 (BACE1) transport to late endosomes, thus increasing the lysosomal degradation of BACE1. Furthermore, PAL diminished 8-hydroxyguanosine (8-OHdG) generation in neuronal mitochondria via enhancing base excision repair (BER), resulting in the attenuation of calpain-1-mediated neuronal loss.. The present data demonstrate that PAL can reduce Aβ generation through accelerating BACE1 lysosomal degradation and can inhibit neuronal loss through suppressing mitochondrial 8-OHdG generation. Hence, PAL might be a promising agent for treating Alzheimer's disease. FUND: This study was financially supported by the Natural Science Foundation of China (U1608282).

Topics: 8-Hydroxy-2'-Deoxyguanosine; Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Brain; Calpain; Disease Models, Animal; Ergocalciferols; Gene Expression Regulation; Humans; Low Density Lipoprotein Receptor-Related Protein-1; Lysosomes; Mice; Mice, Transgenic; Mitochondria; Neurons; Oligopeptides; Presenilin-1; Proteolysis

Vitamin D deficiency is widespread, affecting over 30% of adult Australians, and increasing up to 80% for at-risk groups including the elderly (age>65). The role for Vitamin D in development of the central nervous system is supported by the association between Vitamin D deficiency and incidence of neurological and psychiatric disorders including Alzheimer's disease (AD). A reported positive relationship between Vitamin D status and cognitive performance suggests that restoring Vitamin D status might provide a cognitive benefit to those with Vitamin D deficiency. Mushrooms are a rich source of ergosterol, which can be converted to Vitamin D2 by treatment with UV light, presenting a new and convenient dietary source of Vitamin D2. We hypothesised that Vitamin D2-enriched mushrooms (VDM) could prevent the cognitive and pathological abnormalities associated with dementia. Two month old wild type (B6C3) and AD transgenic (APPSwe/PS1dE9) mice were fed a diet either deficient in Vitamin D2 or a diet which was supplemented with VDM, containing 1±0.2 µg/kg (∼54 IU/kg) vitamin D2, for 7 months. Effects of the dietary intervention on memory were assessed pre- and post-feeding. Brain sections were evaluated for amyloid β (Aβ) plaque loads and inflammation biomarkers using immuno-histochemical methods. Plasma vitamin D metabolites, Aβ40, Aβ42, calcium, protein and cholesterol were measured using biochemical assays. Compared with mice on the control diet, VDM-fed wild type and AD transgenic mice displayed improved learning and memory, had significantly reduced amyloid plaque load and glial fibrillary acidic protein, and elevated interleukin-10 in the brain. The results suggest that VDM might provide a dietary source of Vitamin D2 and other bioactives for preventing memory-impairment in dementia. This study supports the need for a randomised clinical trial to determine whether or not VDM consumption can benefit cognitive performance in the wider population.

Topics: Agaricus; Alzheimer Disease; Amyloid beta-Peptides; Animal Feed; Animals; Brain; Calcium; Cholesterol; Cytokines; Dietary Supplements; Disease Models, Animal; Ergocalciferols; Inflammation; Inflammation Mediators; Liver; Male; Maze Learning; Memory; Mice; Mice, Transgenic; Plaque, Amyloid; Time Factors; Vitamin D

Following contradictory reports, the aim of this study was to apply our highly specific novel assay to delineate the relationship between vitamin D forms and Alzheimer's disease. The study incorporated patients, both untreated and treated with acetylcholinesterase inhibitors, along with controls. Patients were grouped as A: untreated (n=26) and B: treated with donepezil, rivastigmine or galantamine (n=44). The study included a control Group (C, n=35) with no cognitive impairment. Cognitive function was assessed using the MMSE. Levels of vitamin D forms were measured using liquid chromatography-mass spectrometry (LC-MS/MS) and calcium measurements were conducted using inductively coupled plasma-mass spectrometry (ICP-MS). In the cohort studied, no relationship was observed between MMSE score, calcium and any form of vitamin D. The indisputable finding is that the level of 25hydroxyvitamin D2 (25OHD2) (3.165 ± 6.352 nmol/L, p < 0.001) was significantly lower in the untreated Group (A) compared to the control and treated groups (7.932 ± 9.196 and 12.138 ± 15.682 nmol/L, respectively). In contrast, the levels of the primary forms, vitamin D2 and total vitamin D were the highest for the untreated group. Vitamin D levels, assessed as 25OHD are significantly lower in patients suffering from Alzheimer's disease arising from extremely low levels of 25OHD2 along with low levels of 25OHD3. Treatment with acetylcholinesterase inhibitors reverses this deficit. Further research is warranted to delineate the mode of action of acetylcholinesterase inhibitors with respect to normalising 25OHD2 levels. These observations resulted in the hypothesis that along with the common functions of vitamin D, different forms have distinct roles in health and disease.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Chromatography, Liquid; Ergocalciferols; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Tandem Mass Spectrometry; Vitamin D Deficiency

um-related factors were compared in 60 elderly female subjects, who were classified into three groups as nondementia group (n = 18), groups of senile dementia of Alzheimer type (SDAT, n = 22) and of vascular type (VTD, n = 20). The group of SDAT showed significant decrease in serum calcium, and increases in serum parathyroid hormone and urinary Ca, and tendency of decrease in serum 1,25-dihydroxyvitamin D, compared to those of the nondementia group. However, the group of VTD, without showing these features, showed a tendency towards decreased serum calcitonin. These results suggest that Ca and Ca-regulating hormones may play several important and different roles in senile dementia.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Calcitonin; Calcium; Dementia; Dementia, Vascular; Ergocalciferols; Female; Humans; Middle Aged; Parathyroid Hormone; Reference Values