cholecalciferol and Cognition-Disorders

The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear.. To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults.. Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017.. Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270).. The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance.. Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both -0.8 (99% CI, -2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was -0.5 (99% CI, -1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups.. Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes.. ClinicalTrials.gov Identifier: NCT01745263.

Topics: Aged; Aged, 80 and over; Cholecalciferol; Cognition Disorders; Dietary Supplements; Double-Blind Method; Fatty Acids, Omega-3; Female; Follow-Up Studies; Fractures, Bone; Health Status; Humans; Hypertension; Immunity; Male; Physical Fitness; Resistance Training; Treatment Outcome; Vitamins

Type 2 diabetes increases the risk of cognitive decline which adversely impacts self-management of the disease. Evidence also supports a relationship between low serum 25(OH)D levels and poor cognition. The purpose of this trial was to assess vitamin D supplementation on cognitive executive functioning in persons living with type 2 diabetes.. Thirty participants were randomized to either the low-dose allocation (. To our knowledge, this is the first randomized control trial to examine the effects of vitamin D supplementation on cognitive function in people with type 2 diabetes. However, no significant differences in cognitive outcomes between participants who received high-dose therapy and those who received low dose were found.

Topics: Aged; Biomarkers; Chicago; Cholecalciferol; Cognition; Cognition Disorders; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Male; Middle Aged; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women.. Post hoc analysis of a randomized double-blind placebo-controlled trial.. Forty Women's Health Initiative (WHI) clinical centers across the United States.. Four thousand one hundred forty-three women aged 65 and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D Trial and the WHI Memory Study.. Two thousand thirty-four women were randomized to receive 1,000 mg of calcium carbonate combined with 400 IU of vitamin D(3) (treatment) and 2,109 to placebo.. Primary: classifications of probable dementia or mild cognitive impairment (MCI) based on a four-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests.. Mean age of participants was 71. During a mean follow-up of 7.8 years, 39 participants in the treatment group and 37 in the placebo group developed incident dementia (hazard ratio (HR) = 1.11, 95% confidence interval (CI) = 0.71-1.74, P = .64). Likewise, 98 treatment participants and 108 placebo participants developed incident MCI (HR = 0.95, 95% CI = 0.72-1.25, P = .72). There were no significant differences in incident dementia or MCI or in global or domain-specific cognitive function between groups.. There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men, in other age and ethnic groups, and with other doses.

Topics: Aged; Aged, 80 and over; Calcium Carbonate; Cholecalciferol; Cognition; Cognition Disorders; Dietary Supplements; Double-Blind Method; Female; Humans

Patients with Alzheimer's disease (AD) suffer from brain amyloidosis related to defective clearance of amyloid-beta (Abeta) by the innate immune system. To improve the innate immune system of AD patients, we studied immune stimulation of macrophages by 1alpha,25(OH)2-vitamin D3(1,25D3) in combination with curcuminoids. AD patients' macrophages segregate into Type I (positively stimulated by curcuminoids regarding MGAT-III transcription) and Type II (not stimulated). In both Type I and Type II macrophages, 1,25D3 strongly stimulated Abeta phagocytosis and clearance while protecting against apoptosis. Certain synthetic curcuminoids in combination with 1,25D3 had additive effects on phagocytosis in Type I but not Type II macrophages. In addition, we investigated the mechanisms of 1,25D3 and curcuminoids in macrophages. The 1,25D3 genomic antagonist analog MK inhibited 1,25D3 but not curcuminoid effects, suggesting that 1,25D3 acts through the genomic pathway. In silico, 1,25D3 showed preferential binding to the genomic pocket of the vitamin D receptor, whereas bisdemethoxycurcumin showed preference for the non-genomic pocket. 1,25D3 is a promising hormone for AD immunoprophylaxis because in Type I macrophages combined treatment with 1,25D3 and curcuminoids has additive effects, and in Type II macrophages 1,25D3 treatment is effective alone. Human macrophages are a new paradigm for testing immune therapies for AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Cells, Cultured; Cholecalciferol; Cognition Disorders; Curcumin; Diarylheptanoids; Dose-Response Relationship, Drug; Drug Interactions; Female; Gene Expression Regulation; Humans; Liver; Macrophages; Male; Middle Aged; N-Acetylglucosaminyltransferases; Peptide Fragments; Phagocytosis; Protein Structure, Tertiary; Receptors, Calcitriol; Time Factors; Toll-Like Receptor 1; Transfection

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by intracellular neurofibrillary tangles and extracellular Aβ deposition. Growing experimental evidence indicate diverse biological effects of vitamin D

Topics: Alzheimer Disease; Animals; Antioxidants; Behavior, Animal; Cholecalciferol; Cognition; Cognition Disorders; Disease Models, Animal; Hippocampus; Inflammation; Male; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Streptozocin

Complications of diabetes mellitus include cognitive impairments and functional changes in the brain. The present study aimed to investigate the possible beneficial effect of vitamin D3 on episodic memory and cholinergic transmission in the prefrontal cortex of streptozotocin-induced diabetic rats. Thirty male Wistar rats (150-200 g) were included into control, diabetic and diabetic supplemented with vitamin D3 groups. Diabetes was induced by single intraperitoneal injection of streptozotocin 45 mg/kg in citrate buffer. Vitamin D3 was administered orally in a dose of 500 IU/kg/day in corn oil for 10 weeks. Then rats were subjected to novel object recognition test to examine for episodic memory. Animals were sacrificed under diethyl ether anesthesia and prefrontal cortices were dissected to measure the activity of choline acetyl transferase (CAT) and acetyle choline esterase (ACE) enzymes to assess for cholinergic transmission. Diabetic rats spent significantly less time exploring the novel object compared to control animals. Vitamin D3 significantly attenuated the diabetes-induced impairment so that animals again spent significantly more time exploring the novel object. The CAT activity was significantly decreased in diabetic animals while the ACE activity was significantly increased compared to control non-diabetic animals. Diabetes-induced alterations in enzyme activity in the prefrontal cortex were mitigated by vitamin D3 supplementation. The present findings demonstrate the potential effect of vitamin D3 supplementation on cognitive function in diabetic animals. It is possible that this effect is mediated through enhancing the prefrontal cortex cholinergic transmission.

Topics: Acetylcholinesterase; Animals; Cholecalciferol; Choline O-Acetyltransferase; Cognition; Cognition Disorders; Corn Oil; Diabetes Mellitus, Experimental; Dietary Supplements; Discrimination, Psychological; Exploratory Behavior; Male; Memory, Episodic; Prefrontal Cortex; Rats, Wistar; Recognition, Psychology

The aim of this study was to examine the effects of cholecalciferol on systemic inflammation and memory in the setting of fatty liver disease in rats.. To induce the development of fatty liver disease, the rats were fed a 35% fructose solution over 8 weeks. Group I (n=6) was designated as the control group and fed with standard rat chow. Group II (n=6) was provided with, standard rat chow, and 0.3 μg/kg/day of oral cholecalciferol over a duration of 2 weeks. In addition to standard rat chow, group III (n=6) and group IV (n=6) were given 4 mL of the 35% fructose solution per day via oral gavage for 8 weeks. However, group IV was also given 0.3 μg/kg/day of oral cholecalciferol over 2 weeks. After the treatment period, passive avoidance tasks were performed by all groups. The liver and brain were harvested for subsequent biochemical and histopathologic analyses.. The development of fatty liver extends the memory latency period of passively avoiding tasks after 1 trial. Moreover, there were increases in brain TNF-α and plasma MDA levels according to two-way analysis of variance. Cholecalciferol supplementation decreased the latency period of passively avoiding tasks in rats with hepatosteatosis, and also significantly reduced brain TNF-α and plasma MDA levels.. Fatty liver may contribute to the development of systemic inflammation, which affects cognition and causes deficits in memory; however, the anti-inflammatory and antioxidant properties of vitamin D may improve the cognitive function of rats with hepatosteatosis.

Topics: Administration, Oral; Animals; Avoidance Learning; Cholecalciferol; Cognition Disorders; Disease Models, Animal; Fatty Liver; Inflammation; Inflammation Mediators; Male; Metabolic Syndrome; Rats; Rats, Sprague-Dawley

Vitamin D3 (cholecalciferol) deficiency has been associated with dementia and cognitive decline. Which cognitive domains are most associated with D3 levels and how seasonal fluctuations in levels relate to cognition is unclear. We addressed these questions using a prospective observational study examining associations between D3 levels and cognition among individuals living in northern latitudes (54°N) in summer and winter.. Healthy adult participants underwent testing in summer and winter of D3 levels and cognition, using the Symbol digit Modalities test, phonemic fluency, digit Span and CANTAB battery.. Of 32 participants tested in the summer, 46% were D3 insufficient (<75 nmol/L) and performed worse on digit Span Backward (DS-B) (μ=5.8, SD=2) than those who were sufficient (μ=7.9, SD=2), p=0.018. In multivariate analyses, sufficiency status was an independent predictor of dS-B, (b=0.41, p=0.02). The majority (63%) of 19 participants tested in winter were D3 insufficient, with levels declining by a median of 15 nmol/L overall. Those with insufficient levels performed worse (i.e., higher scores) on the CANTAB Spatial Working Memory (SWM) task (μ=36.1, SD=6 versus μ=29.3, SD=8), p=0.05). Those with larger drops in levels (≥15 nmol/L) showed decline/less improvement on the CANTAB one touch Stockings of Cambridge (OTS) task, (μ=0.50, SD=1.9 versus μ=-2.11, SD=2.6, p=0.01), a test of working memory/executive functioning.. Vitamin D3 insufficiency and seasonal declines ≥15 nmol/L were associated with inferior working memory/executive functioning. While our findings require confirmation, they suggest that sufficient D3 levels should be maintained year-round, likely necessitating supplementation, at least during winter at higher latitudes.

Topics: Adult; Aged; Cholecalciferol; Cognition Disorders; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Seasons; Vitamin D Deficiency; Young Adult

To examine the relationship of serum 25-hydroxy vitamin D3 with cognitive functioning in higher age, using an instrument covering multiple cognitive domains in a population-based study.. Follow-up study with measurement of vitamin D levels at baseline and assessment of cognitive functioning at year 5 follow-up.. A subgroup of 1639 participants of the ongoing epidemiological ESTHER study of the elderly general population in Saarland State, Germany, aged 65+ years at baseline (2000-2002).. Observational study.. Cognitive functioning was assessed by the COGTEL phone interview developed by Kliegel et al., which was administered 5 years after ESTHER baseline. Vitamin D in baseline samples was measured by chemiluminescence methods. Additional information was obtained by standardised questionnaires.. In multiple linear regression adjusted for important confounders, women in the lowest sex-specific quintile of vitamin D showed an on average 2.1 (95% confidence interval: 0.4 to 3.9) units lower COGTEL score than women in the highest quintile. A similar, albeit slightly weaker, association was seen in males (difference of 1.7 [-0.4 to 3.8] units). Spline regression suggested non-linearity with a distinct decline in cognitive performance in the lower range of vitamin D levels.. Our findings support suggestions that low levels of vitamin D may be associated with reduced cognitive functioning in the elderly.

Topics: Aged; Cholecalciferol; Cognition Disorders; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Germany; Humans; Male; Prospective Studies; Risk Factors; Socioeconomic Factors; Vitamin D Deficiency