Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial.
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SUBMITTER: Kang JH
PROVIDER: S-EPMC8636504 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLittle is known regarding the association of interviewer-reported cognitive problems (ICP) with age-related cognitive decline. We aimed to investigate the independent associations of ICP and the combined associations of ICP and self-reported cognitive problems (SCP) with subsequent cognitive decline and dementia in two prospective cohort studies.MethodsWe included 10,976 Chinese (age = 57.7 ± 8.7) and 40,499 European (age = 64.6 ± 9.4) adults without dementia from the China Health and Retirement Longitudinal Study (CHARLS) and the Survey of Health, Ageing, and Retirement in Europe (SHARE). Self-rated memory (5-point scale) and interviewer-rated frequencies of asking for clarification (6-point scale) were used to define SCP and ICP (dichotomized). Outcomes included objective cognitive test scores (z-score transformation) and incident dementia. Generalized estimating equation models were performed to evaluate mean differences in objective cognitive decline. Logistic and Cox regression models were used to estimate the relative risk of dementia. Results from two cohorts were pooled using the random-effects models.ResultsICP was associated with faster cognitive decline in CHARLS (βCHARLS = -0.025 [-0.044, -0.006] z-score/year). ICP and SCP were also independently associated with higher risk of dementia in two cohorts (pooled relative risk for SCP = 1.73 [1.30, 2.29]; pooled relative risk for ICP = 1.40 [1.10, 1.79]). In the joint analysis, participants with coexistence of SCP and ICP had the fastest cognitive decline (βCHARLS = -0.051 [-0.080, -0.021]; βSHARE = -0.024 [-0.043, -0.004]; pooled β = -0.035 [-0.061, -0.009] z-score/year) and highest risk of dementia (ORCHARLS = 1.77 [1.42, 2.20]; HRSHARE = 2.94 [2.42, 3.59]; pooled relative risk = 2.29 [1.38, 3.77]).ConclusionsThe study suggested that interviewer-reported cognitive problems may be early indicators of cognitive decline and dementia in middle-aged and older adults. A combination of self- and interviewer-reported cognitive problems showed the strongest associations with cognitive decline and dementia.
| S-EPMC10792911 | biostudies-literature
Project description:BackgroundVitamin D deficiency has been linked with dementia risk, cognitive decline, and executive dysfunction. However, the association with memory remains largely unknown.ObjectiveTo investigate whether low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with memory decline.MethodsWe used data on 1,291 participants from the US Cardiovascular Health Study (CHS) and 915 participants from the Dutch Longitudinal Aging Study Amsterdam (LASA) who were dementia-free at baseline, had valid vitamin D measurements, and follow-up memory assessments. The Benton Visual Retention Test (in the CHS) and Rey's Auditory Verbal Learning Test (in the LASA) were used to assess visual and verbal memory, respectively.ResultsIn the CHS, those moderately and severely deficient in serum 25(OH)D changed -0.03 SD (95% CI: -0.06 to 0.01) and -0.10 SD (95% CI: -0.19 to -0.02) per year respectively in visual memory compared to those sufficient (p = 0.02). In the LASA, moderate and severe deficiency in serum 25(OH)D was associated with a mean change of 0.01 SD (95% CI: -0.01 to 0.02) and -0.01 SD (95% CI: -0.04 to 0.02) per year respectively in verbal memory compared to sufficiency (p = 0.34).ConclusionsOur findings suggest an association between severe vitamin D deficiency and visual memory decline but no association with verbal memory decline. They warrant further investigation in prospective studies assessing different memory subtypes.
| S-EPMC5525144 | biostudies-literature
Project description:RationaleAlthough vitamin D is widely used to promote skeletal health, definitive data on benefits and risks of supplemental vitamin D alone on bone are lacking. Results from large, randomized controlled trials in the general population are sparse. Data on the effects of supplemental omega-3 fatty acids (FAs) on bone are also limited.DesignThe VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled trial assessing the role of vitamin D3 (2000 IU/d) and omega-3 FA (1g/d) supplements in reducing risks of cancer and cardiovascular disease among U.S. men aged ≥50 and women aged ≥55. To comprehensively test effects of supplemental vitamin D and/or omega-3 FAs on skeletal health, the VITAL: Effects on Fractures ancillary study is determining the effects of these supplements on incident fractures among 25,875 participants enrolled in the parent trial. Study investigators adjudicate fractures through a detailed review of medical records and radiological images (hip and femur). In a complementary ancillary, VITAL: Effects on Structure and Architecture is determining the effects of supplemental vitamin D and/or omega-3 FAs on bone with detailed phenotyping during in-person visits. Comprehensive assessments of bone density, turnover, structure/architecture, body composition, and physical performance are being performed at baseline and 2 years post-randomization.ConclusionResults from these studies will clarify the relationship between supplemental vitamin D and/or omega-3 FAs on bone health outcomes, and inform clinical care and public health guidelines on the use of supplemental vitamin D for the primary prevention of fractures in women and men.
| S-EPMC4380672 | biostudies-literature
Project description:Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5-6 months, middle-aged F344 rats were fed diets containing low, medium (typical amount) or high vitamin D3 (100, 1000 or 10,000 IU/kg diet, respectively) and then hippocampal-dependent learning and memory were tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication and G-protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function and suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging. Sixty, middle-aged male F344 rats were divided into three groups, each receiving for 5-6 months a different dietary amount of cholecalciferol (vitamin D3; VitD3). Purified AIN-93G (Harlan-Teklad) diet was modified to contain low, medium or high VitD3 (IU/kg diet): High = 10,000, Standard (Control) = 1000; Low = 100. Animal weight and amount of food consumed was recorded 2-3 times/week. Serum levels of 25-hydroxy vitamin D were determined using liquid chromatography/tandem mass spectrometry (ZRT Laboratory). Hippocampal RNA was isolated, quantified and checked for RNA integrity. One low VitD3 sample failed RNA quality control. Remaining RNA samples were applied to Affymetrix Rat Gene 1.0 ST arrays (one array/subject). Pre-statistical filtering removed poorly annotated probe sets, low intensity signals, and outlier values (>2SD of the group mean). Filtered data were analyzed by 1-way ANOVA to identify significant differences and the False Discovery Rate (FDR) procedure was used to estimate the error of multiple testing. FDR was compared at 0.31 and 0.17. Significant genes were assigned to one of four idealized expression patterns using Pearson’s test and separated by the sign of their correlation; relative gene expression values are provided on the log-2 scale. Functional categorization for significant genes was determined using DAVID bioinformatic tools. Please note that 'Marked' and 'Unmarked' (in the sample titles) refers to whether the rat had a mark on its tail. The rats were pair-housed and this is how two rats in one cage were distinguished.
2014-09-23 | E-GEOD-61326 | biostudies-arrayexpress
Project description:Objectives: Elevated plasma total homocysteine (tHcy) is associated with increased risk of cardiovascular disease, stroke and dementia. Results of clinical trials using B-vitamins to reduce the cognitive risks attributed to tHcy have been inconsistent. The high prevalence of both hyperhomocysteinemia and cognitive impairment among kidney transplant recipients makes them an important population in which to evaluate the effect of lowering homocysteine on cognitive function. We therefore evaluated whether B-vitamin therapy to lower tHcy would prevent cognitive-decline in a cohort of stable kidney transplant recipients.The study was a longitudinal ancillary of the FAVORIT trial, a randomized, placebo-controlled multi-site trial of high-dose B vitamins to reduce cardiovascular and cerebrovascular events in clinically stable kidney transplant recipients with elevated tHcy.584 participants from 18 sites across North America.The intervention consisted of a daily multivitamin containing high-doses of folate (5.0 mg), vitamin B12 (1.0 mg) and vitamin B6 (50 mg). The placebo consisted of a daily multi-vitamin containing no folate and recommended daily allowances of vitamins B12 and B6 (0 mg folate; 2.0 µg vitamin B12; 1.4 mg vitamin B6).Annual neuropsychological assessment for up to 5 years (mean 3.3 years) using a standardized test battery. Efficacy was analyzed on an intention-to-treat basis using end-of-trial data. Subgroup analyses included stratification for baseline plasma B-vitamin and tHcy concentrations.At baseline, cognitive impairment was common with 61% of participants falling more than one standard deviation below published norms for at least one cognitive test. Fewer than 1% of participants had insufficient plasma folate < 5 ng/ml or vitamin B12 < 148 pmol/L. However, 44.6% had plasma B6 concentrations < 30 nmol/L. At follow-up, processing speed and memory scores were modestly but significantly better in the B-vitamin supplement group than in controls (p?0.05). There was no interaction between baseline tHcy, B-vitamin status and treatment on the cognitive outcomes.High-dose B-vitamin supplementation provided modest cognitive benefit for kidney transplant recipients with elevated baseline tHcy. Since nearly all participants were folate and vitamin B12 sufficient at baseline, the potential cognitive benefits of folate and B12 supplementation in individuals with poor B-vitamin status remains to be determined.
| S-EPMC5724781 | biostudies-literature
Project description:BackgroundObservational studies among older women have associated vitamin D insufficiency with a greater prevalence and incidence of urinary incontinence. However, little is known about the effect of vitamin D supplementation in reducing urinary incontinence.ObjectiveThis study aimed to evaluate the effects of vitamin D supplementation in reducing the frequency of urinary incontinence in older women.Study designWe conducted an ancillary study of women aged ≥55 years in the Vitamin D and Omega-3 Trial, a randomized trial with a 2×2 factorial design. Recruitment of participants started from 2011 to 2014 across 50 US states, and the follow-up of participants ended in January 2018. Randomized treatments in the parent study included (1) vitamin D3 (cholecalciferol) at a dosage of 2000 IU/d, (2) marine omega-3 fatty acids at a dosage of 1 g/d, and (3) matching placebo. Here, we analyzed women according to their randomization to vitamin D supplementation or placebo, regardless of treatment with omega-3 fatty acid supplementation. Validated frequency of urinary incontinence questions were added in year 2 of the study and were used again in year 5 at the end of trial. Prespecified ancillary outcomes included the prevalence of urinary incontinence at years 2 and 5, along with incident incontinence and progression of incontinence (from lower to higher frequency) from year 2 to year 5. Preplanned subgroup analyses examined the following outcomes: prerandomization of low serum levels of vitamin D (serum 25-hydroxyvitamin D<20 ng/mL), incontinence types, weight categories, and African American race.ResultsAmong the randomized women who provided urinary incontinence data, 11,646 women at year 2 and 10,527 women at year 5, the mean age was 70 years at year 2, with 29% racial and ethnic minorities. The prevalence of urinary incontinence that occurred at least weekly was 29% at year 2 and increased to 37% at year 5. Vitamin D supplementation compared to with placebo was not associated with lower odds of urinary incontinence occurring at least weekly at year 2 (odds ratio, 1.08; 95% confidence interval, 0.99-1.19) or year 5 (odds ratio, 1.04; 95% confidence interval, 0.94-1.15). Vitamin D supplementation compared to placebo was not associated with lower incidence or progression of urinary incontinence from year 2 to year 5: incidence (odds ratio, 1.06; 95% confidence interval, 0.83-1.35) or progression (odds ratio, 0.94; 95% confidence interval, 0.82-1.08). Women with prerandomization of low serum levels of vitamin D (n=836) did not have lower odds of the prevalence, incidence, or progression of urinary incontinence. The findings were null in subgroups according to incontinence type, women with obesity, and African American women. Only women with healthy weight randomized to vitamin D had lower odds of progression of urinary incontinence (odds ratio, 0.78; 95% confidence interval, 0.63-0.95; P=.01).ConclusionVitamin D supplementation compared to placebo for 2 to 5 years was not associated with differences in the prevalence, incidence, or progression of urinary incontinence in older women with and without adequate serum vitamin D levels, with inconsistent differences among subgroups. The findings showed that the broad use of moderate doses of vitamin D supplementation did not reduce urinary incontinence in older women.
| S-EPMC8983596 | biostudies-literature
Project description:Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline.To determine the efficacy and safety of B vitamin supplementation in the treatment of AD.A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States.Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months.Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog).A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements.This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD.clinicaltrials.gov Identifier: NCT00056225.
| S-EPMC2684821 | biostudies-literature
Project description:Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5-6 months, middle-aged F344 rats were fed diets containing low, medium (typical amount) or high vitamin D3 (100, 1000 or 10,000 IU/kg diet, respectively) and then hippocampal-dependent learning and memory were tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication and G-protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function and suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging.
2014-09-23 | GSE61326 | GEO
Project description:ImportanceEpidemiologic and trial data suggest that vitamin D supplementation may reduce metastatic cancer and cancer mortality, reflecting shared biological pathways.ObjectiveTo follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advanced (metastatic or fatal) cancer and an examination possible effect modification by body mass index.Design, setting, and participantsVITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial of vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d). This multicenter clinical trial was conducted in the United States; participants included men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease at baseline. Randomization took place from November 2011 through March 2014, and study medication ended on December 31, 2017. Data for this secondary analysis were analyzed from November 1, 2011, to December 31, 2017.InterventionsVitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d) supplements.Main outcomes and measuresFor the present analysis, the primary outcome was a composite incidence of metastatic and fatal invasive total cancer, because the main VITAL study showed a possible reduction in fatal cancer with vitamin D supplementation and effect modification by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for total cancer incidence reduction for individuals with normal BMI, but not for individuals with overweight or obesity. Secondary analyses included examination of BMI (<25, 25 to < 30, and ≥30) as effect modifiers of the observed associations.ResultsAmong 25 871 randomized VITAL participants (51% female; mean [SD] age, 67.1 [7.1] years), 1617 were diagnosed with invasive cancer over a median intervention period of 5.3 years (range, 3.8-6.1 years). As previously reported, no significant differences for cancer incidence by treatment arm were observed. However, a significant reduction in advanced cancers (metastatic or fatal) was found for those randomized to vitamin D compared with placebo (226 of 12 927 assigned to vitamin D [1.7%] and 274 of 12 944 assigned to placebo [2.1%]; HR, 0.83 [95% CI, 0.69-0.99]; P = .04). When stratified by BMI, there was a significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with normal BMI (BMI<25: HR, 0.62 [95% CI, 0.45-0.86]) but not among those with overweight or obesity (BMI 25-<30: HR, 0.89 [95% CI, 0.68-1.17]; BMI≥30: HR, 1.05 [95% CI, 0.74-1.49]) (P = .03 for interaction by BMI).Conclusions and relevanceIn this randomized clinical trial, supplementation with vitamin D reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with the strongest risk reduction seen in individuals with normal weight.Trial registrationClinicalTrials.gov Identifier: NCT01169259.
| S-EPMC7675103 | biostudies-literature
Project description:We test the idea that peripheral cellular senescence is a major driver of age-related cognitive impairment, such that treatment with the brain impermeable senolytic, ABT-263, can preserve cognition and markers of brain aging thought to underlie cognitive decline. Male F344 rats were treated from 12-18 months of age with quercetin + dasatinib or ABT-263 or vehicle and were compared to young (6 month). Senolytic treatments had similar effects in decreasing peripheral markers of senescence and the senescence-associated secretory phenotype (SASP), including plasma levels of several cytokines, rescued memory and hippocampal synaptic transmission, and decreased expression of immune response genes in the dentate gyrus (DG). Across senolytic treatment groups, differential DG gene expression was observed for cellular senescence and pathways linked to senescence, including negative regulation of cell death, ribosomes, and microglial activation consistent with differential access of dasatinib and ABT-263 to the brain. Finally, both senolytic treatments preserved the blood-brain barrier suggesting that leakage of clinically significant amounts of ABT-263 into the brain is unlikely. The results indicate that preserved cognition was due to removal of peripheral senescent cells, decreasing systemic inflammation that normally drives neuroinflammation, BBB breakdown, and impaired synaptic function.
2023-06-07 | GSE220971 | GEO