Total Choline Research Articles

Strength gains after 12 weeks of resistance training correlate with neurochemical markers of brain health in older adults: a randomized control 1H-MRS study

Physical exercise is considered a potent countermeasure against various age-associated physiological deterioration processes. We therefore assessed the effect of 12 weeks of resistance training on brain metabolism in older adults (age range: 60–80 years). Participants either underwent two times weekly resistance training program which consisted of four lower body exercises performed for 3 sets of 6–10 repetitions at 70–85% of 1 repetition maximum (n = 20) or served as the passive control group (n = 21). The study used proton magnetic resonance spectroscopy to quantify the ratio of total N-acetyl aspartate, total choline, glutamate-glutamine complex, and myo-inositol relative to total creatine (tNAA/tCr, tCho/tCr, Glx/tCr, and mIns/tCr respectively) in the hippocampus (HPC), sensorimotor (SM1), and prefrontal (dlPFC) cortices. The peak torque (PT at 60°/s) of knee extension and flexion was assessed using an isokinetic dynamometer. We used repeated measures time × group ANOVA to assess time and group differences and correlation coefficient analyses to examine the pre-to-post change (∆) associations between PT and neurometabolite variables. The control group showed significant declines in tNAA/tCr and Glx/tCr of SM1, and tNAA/tCr of dlPFC after 12 weeks, which were not seen in the experimental group. A significant positive correlation was found between ∆PT knee extension and ∆SM1 Glx/tCr, ∆dlPFC Glx/tCr and between ∆PT knee flexion and ∆dlPFC mIns/tCr in the experimental group. Overall, findings suggest that resistance training seems to elicit alterations in various neurometabolites that correspond to exercise-induced “preservation” of brain health, while simultaneously having its beneficial effect on augmenting muscle functional characteristics in older adults.

Choline Intake and Cognitive Function Among U.S. Older Adults

Choline is an essential nutrient affects brain development in early life. However, evidence is lacking regarding its potential neuroprotective effects in later life from community-based cohorts. This study assessed the relationship between choline intake and cognitive functioning in a sample of older adults 60 years + from the National Health and Nutrition Examination Survey 2011–2012 and 2013–2014 waves (n = 2,796). Choline intake was assessed using two nonconsecutive 24-hour dietary recalls. Cognitive assessments included immediate and delayed word recalls, Animal Fluency, and Digit Symbol Substitution Test. The average daily dietary choline intake was 307.5 mg, and the total intake (including intake from dietary supplements) was 330.9 mg, both below the Adequate Intake level. Neither dietary OR = 0.94, 95% CI (0.75, 1.17) nor total choline intake OR = 0.87, 95% CI (0.70, 1.09) was associated with changes in cognitive test scores. Further investigation adopting longitudinal or experimental designs may shed light on the issue.

In vivo cortical glutathione response to oral fumarate therapy in relapsing-remitting multiple sclerosis: A single-arm open-label phase IV trial using 7-Tesla 1H MRS

BackgroundThis is an open-label, single-arm, single-center pilot study using 7-Tesla in vivo proton magnetic resonance spectroscopy (1H MRS) to measure brain cortical glutathione concentration at baseline before and during the use of oral fumarates as a disease-modifying therapy for multiple sclerosis. The primary endpoint of this research was the change in prefrontal cortex glutathione concentration relative to a therapy-naïve baseline after one year of oral fumarate therapy. MethodsBrain glutathione concentrations were examined by 1H MRS in single prefrontal and occipital cortex cubic voxels (2.5 × 2.5 × 2.5 cm3) before and during initiation of oral fumarate therapy (120 mg b.i.d. for 7 days and 240 mg b.i.d. thereafter). Additional measurements of related metabolites glutamate, glutamine, myoinositol, total N-acetyl aspartate, and total choline were also acquired in voxels centered on the same regions. Seven relapsing-remitting multiple sclerosis patients (4 f / 3 m, age range 28–50 years, mean age 40 years) naïve to fumarate therapy were scanned at pre-therapy baseline and after 1, 3, 6 and 12 months of therapy. A group of 8 healthy volunteers (4 f / 4 m, age range 33–48 years, mean age 41 years) was also scanned at baseline and Month 6 to characterize 1H-MRS measurement reproducibility over a comparable time frame. ResultsIn the multiple sclerosis cohort, general linear models demonstrated a significant positive linear relationship between prefrontal glutathione and time either linearly across all time points (+0.05 ± 0.02 mM/month, t(27) = 2.6, p = 0.02) or specifically for factor variable Month 12 (+0.6 ± 0.3 mM/12 months, t(24) = 2.2, p = 0.04) relative to baseline. No such effects of time on glutathione concentration were demonstrated in the occipital cortex or in the healthy volunteer group. Changes in occipital total choline were further observed in the multiple sclerosis cohort as well as prefrontal total choline and occipital glutamine and myoinositol in the control cohort throughout the study duration. ConclusionsWhile the open-label single-arm pilot study design and abbreviated control series cannot support firm conclusions about the influence of oral fumarate therapy independent of test–retest factors or normal biological variation in a state of either health or disease, these results do justify further investigation at a larger scale into the potential relationship between prefrontal cortex glutathione increases and oral fumarate therapy in relapsing-remitting multiple sclerosis.

Neurometabolic correlates of posturography in normal aging and older adults with mild cognitive impairment: Evidence from a 1H-MRS study

Proton magnetic resonance spectroscopy (1H-MRS) holds promise for revealing and understanding neurodegenerative processes associated with cognitive and functional impairments in aging. In the present study, we examined the neurometabolic correlates of balance performance in 42 cognitively intact older adults (healthy controls - HC) and 26 older individuals that were diagnosed with mild cognitive impairment (MCI). Neurometabolite ratios of total N-acetyl aspartate (tNAA), glutamate-glutamine complex (Glx), total choline (tCho) and myo-inositol (mIns) relative to total creatine (tCr) were assessed using single voxel 1H-MRS in four different brain regions. Regions of interest were the left hippocampus (HPC), dorsal posterior cingulate cortex (dPCC), left sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (dlPFC). Center-of-pressure velocity (Vcop) and dual task effect (DTE) were used as measures of balance performance. Results indicated no significant group differences in neurometabolite ratios and balance performance measures. However, our observations revealed that higher tCho/tCr and mIns/tCr in hippocampus and dPCC were generic predictors of worse balance performance, suggesting that neuroinflammatory processes in these regions might be a driving factor for impaired balance performance in aging. Further, we found that higher tNAA/tCr and mIns/tCr and lower Glx/tCr in left SM1 were predictors of better balance performance in MCI but not in HC. The latter observation hints at the possibility that individuals with MCI may upregulate balance control through recruitment of sensorimotor pathways.

Altered neurometabolite levels in the brains of patients with depression: A systematic analysis of magnetic resonance spectroscopy studies

BackgroundNumerous magnetic resonance spectroscopy (MRS) studies have reported metabolic abnormalities in the brains of patients with depression, although inconsistent results have been reported. The aim of this study was to explore changes in neurometabolite levels in patients with depression across large-scale MRS studies. MethodA total of 307 differential metabolite entries associated with depression were retrieved from 180 MRS studies retrieved from the Metabolite Network of Depression Database. The vote-counting method was used to identify consistently altered metabolites in the whole brain and specific brain regions of patients with depression. ResultsOnly few differential neurometabolites showed a stable change trend. The levels of total choline (tCho) and the tCho/N-acetyl aspartate (NAA) ratio were consistently higher in the brains of patients with depression, and that the levels of NAA, glutamate and glutamine (Glx), and gamma-aminobutyric acid (GABA) were lower. For specific brain regions, we found lower Glx levels in the prefrontal cortex and lower GABA concentrations in the occipital cortex. We also found lower concentrations of NAA in the anterior cingulate cortex and prefrontal cortex. The levels of tCho were higher in the prefrontal cortex and putamen. ConclusionOur results revealed that most altered neurometabolites in previous studies lack of adequate reproducibility. Through vote-counting method with large-scale studies, downregulation of glutamatergic neurometabolites, impaired neuronal integrity, and disturbed membrane metabolism were found in the pathobiology of depression, which contribute to existing knowledge of neurometabolic changes in depression. Further studies based on a larger dataset are needed to confirm our findings.

Short-term neurochemical effects of transcutaneous trigeminal nerve stimulation using 7T magnetic resonance spectroscopy.

The purpose was to explore the effects of transcutaneous trigeminal nerve stimulation (TNS) on neurochemical concentrations (brainstem, anterior cingulate cortex [ACC], dorsolateral prefrontal cortex [DLPFC], ventromedial prefrontal cortex [VMPFC], and the posterior cingulate cortex [PCC]) using ultrahigh-field magnetic resonance spectroscopy. This double-blinded study tested 32 healthy males (age: 25.4±7.3years) on two separate occasions where participants received either a 20-minute TNS or sham session. Participants were scanned at baseline and twice post-TNS/sham administration. There were no group differences in concentration changes of glutamate, gamma-aminobutyric acid, glutamine, myoinositol (mI), total N-acetylaspartate, total creatine (tCr), and total choline between the baseline scan and the first post-TNS/sham scan and between the first and second post-TNS/sham scan in the brainstem, ACC, DLPFC, VMPFC, and PCC. Between the baseline scan and the second post-TNS/sham scan, changes in tCr (mean difference=0.280mM [0.075 to 0.485], p=.026) and mI (mean difference=0.662mM [0.203 to 1.122], p=.026) in the DLPFC differed between groups. Post hoc analyses indicated that there was a decrease in tCr (mean change=-0.201mM [-0.335 to -0.067], p=.003) and no change in mI (mean change=-0.327mM [-0.737 to 0.083], p=.118) in the TNS group; conversely, there was no change in tCr (mean change=-0.100mM [-0.074 to 0.274], p=.259) and an increase in mI (mean change=0.347mM [0.106 to 0.588], p=.005) in the sham group. These data demonstrate that a single session of unilateral TNS slightly decreased tCr concentrations in the DLPFC region.

Changes in plasma and milk choline metabolite concentrations in response to the provision of various rumen-protected choline prototypes in lactating dairy cows.

Choline feeding in the form of rumen-protected choline (RPC) has been shown to increase milk production and improve measures of metabolic health (e.g., liver triglyceride) in dairy cows. The objective was to characterize changes in plasma and milk choline and choline metabolite concentrations, including microbial-derived trimethylamine N-oxide (TMAO), in response to increasing ruminal spot-doses, different types of RPC, and ruminal stability of RPC in lactating cows. For experiment 1, 12 mid-lactation (121 ± 16.3 d in milk) Holstein cows were balanced by total plasma choline concentrations and milk yields. Cows were assigned to 1 of 3 lipid-encapsulated RPC products (main plots): prototypes P1, P2, and P3 (containing 59, 56, and 30% choline chloride, respectively). Within each main plot, cows were assigned to a sequence of doses in a 4 × 4 Latin square design: 0, 18, 36, or 54 g of choline chloride. Treatments were preconditioned with ground corn and administered as a single ruminal bolus once per experimental period 1 h postfeeding of a total mixed ration. For experiment 2, we compared a control (0 g of choline chloride) versus P2, and P4 and P5 (60 and 62% choline chloride, respectively) in a repeated 4 × 4 Latin square design. Experiment 2 followed a similar design as experiment 1 with modifications: 12 late-lactation (228 ± 7.10 d in milk) Holstein cows were used; treatments were administered as part of a premeal; and cows received a daily allowance of a total mixed ration as equal provisions every 4 h within 24 h before and after treatment. For both experiments, plasma and milk samples were collected for choline and choline metabolite quantification. Data were analyzed using a mixed model including fixed effects of treatment, period, and time. Contrast statements were used to test for linearity of dose and differences between prototypes for experiment 1 and 2, respectively. Plasma and milk TMAO concentrations increased with RPC dose (peak by h). Milk choline and betaine yields increased with RPC dose in a quadratic manner; albeit, dependent upon RPC type. Milk phosphocholine (PCho) and glycerophosphorylcholine (GPC) yields changed by select RPC dose (experiment 1), however Met, PCho, GPC, phosphatidylcholine, and total choline concentrations in milk, and plasma Met and sphingomyelin concentrations were not responsive. We conclude that plasma or milk choline, betaine, and TMAO concentrations are responsive to RPC type, dose, and stage of lactation evaluated.

Integrating Neuroimaging Measures in Nursing Research.

Medical and scientific advancement worldwide has led to a longer lifespan. With the population aging comes the risk of developing cognitive decline. The incorporation of neuroimaging measures in evaluating cognitive changes is limited in nursing research. The aim of this review is to introduce nurse scientists to neuroimaging measures employed to assess the association between brain and cognitive changes. Relevant literature was identified by searching CINAHL, Web of Science, and PubMed databases using the following keywords: "neuroimaging measures," "aging," "cognition," "qualitative scoring," "cognitive ability," "molecular," "structural," and "functional." Neuroimaging measures can be categorized into structural, functional, and molecular imaging approaches. The structural imaging technique visualizes the anatomical regions of the brain. Visual examination and volumetric segmentation of select structural sequences extract information such as white matter hyperintensities and cerebral atrophy. Functional imaging techniques evaluate brain regions and underlying processes using blood-oxygen-dependent signals. Molecular imaging technique is the real-time visualization of biological processes at the cellular and molecular levels in a given region. Examples of biological measures associated with neurodegeneration include decreased glutamine level, elevated total choline, and elevated Myo-inositol. Nursing is at the forefront of addressing upstream factors impacting health outcomes across a lifespan of a population at increased risk of progressive cognitive decline. Nurse researchers can become more facile in using these measures both in qualitative and quantitative methodology by leveraging previously gathered neuroimaging clinical data for research purposes to better characterize the associations between symptom progression, disease risk, and health outcomes.

Inadequate Choline Intake in Pregnant Women in Germany.

Choline is an essential nutrient that is involved in various developmental processes during pregnancy. While the general adequate choline intake (AI) for adults has been set at 400 mg/day by the European Food Safety Authority (EFSA), an AI of 480 mg/day has been derived for pregnant women. To date, the choline intake of pregnant women in Germany has not been investigated yet. Therefore, in this survey, the total choline intake from dietary and supplementary sources in pregnant women was estimated using an online questionnaire. A total of 516 pregnant women participated in the survey, of which 283 met the inclusion criteria (13 to 41 weeks of gestational age, 19-45 years). 224 (79%) of the participants followed an omnivorous diet, 59 (21%) were vegetarian or vegan. Median choline intake was 260.4 (±141.4) mg/day, and only 19 women (7%) achieved the adequate choline intake. The median choline intake of omnivores was significantly higher than that of vegetarians/vegans (269.5 ± 141.5 mg/day vs. 205.2 ± 101.2 mg/day; p < 0.0001). 5% (13/283) of pregnant women took choline-containing dietary supplements. In these women, dietary supplements provided 19% of the total choline intake. Due to the importance of choline for the developmental processes during pregnancy, the study results prove the urgent need for an improved choline supply for pregnant women.

Feasibility and implications of using subject-specific macromolecular spectra to model short echo time magnetic resonance spectroscopy data.

Expert consensus recommends linear-combination modeling (LCM) of 1 H MR spectra with sequence-specific simulated metabolite basis function and experimentally derived macromolecular (MM) basis functions. Measured MM basis functions are usually derived from metabolite-nulled spectra averaged across a small cohort. The use of subject-specific instead of cohort-averaged measured MM basis functions has not been studied widely. Furthermore, measured MM basis functions are not widely available to non-expert users, who commonly rely on parameterized MM signals internally simulated by LCM software. To investigate the impact of the choice of MM modeling, this study, therefore, compares metabolite level estimates between different MM modeling strategies (cohort-mean measured; subject-specific measured; parameterized) in a lifespan cohort and characterizes its impact on metabolite-age associations. 100 conventional (TE = 30 ms) and metabolite-nulled (TI = 650 ms) PRESS datasets, acquired from the medial parietal lobe in a lifespan cohort (20-70 years of age), were analyzed in Osprey. Short-TE spectra were modeled in Osprey using six different strategies to consider the MM baseline. Fully tissue- and relaxation-corrected metabolite levels were compared between MM strategies. Model performance was evaluated by model residuals, the Akaike information criterion (AIC), and the impact on metabolite-age associations. The choice of MM strategy had a significant impact on the mean metabolite level estimates and no major impact on variance. Correlation analysis revealed moderate-to-strong agreement between different MM strategies (r > 0.6). The lowest relative model residuals and AIC values were found for the cohort-mean measured MM. Metabolite-age associations were consistently found for two major singlet signals (total creatine (tCr])and total choline (tCho)) for all MM strategies; however, findings for metabolites that are less distinguishable from the background signals associations depended on the MM strategy. A variance partition analysis indicated that up to 44% of the total variance was related to the choice of MM strategy. Additionally, the variance partition analysis reproduced the metabolite-age association for tCr and tCho found in the simpler correlation analysis. In summary, the inclusion of a single high signal-to-noise ratio MM basis function (cohort-mean) in the short-TE LCM leads to more lower model residuals and AIC values compared with MM strategies with more degrees of freedom (Gaussian parametrization) or subject-specific MM information. Integration of multiple LCM analyses into a single statistical model potentially allows to identify the robustness in the detection of underlying effects (e.g., metabolite vs. age), reduces algorithm-based bias, and estimates algorithm-related variance.

Brain proton magnetic resonance spectroscopy in patients with Parkinson's disease.

Background: The accuracy of current laboratory and imaging studies for diagnosis and monitoring of Parkinson's disease (PD) severity is low and diagnosis is mainly dependent on clinical examination. Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique that can assess the chemical profile of the brain. In this study, we evaluated the utility of proton MRS in diagnosis of PD and determination of its severity. Methods: Patients with PD and healthy age-matched controls were studied using proton MRS. The level of N-acetylaspartate (NAA), total creatine (Cr), and total choline (Cho), and their ratios were calculated in substantia nigra (SN), putamen (Pu), and motor cortex. PD severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr scale. Results: Compared to 25 healthy controls (18 men, age: 59.00 ± 8.39 years), our 30 patients with PD (24 men, age: 63.80 ± 12.00 years, 29 under treatment) showed no significant difference in the metabolite ratios in SN, Pu, and motor cortex. Nigral level of NAA/Cr was significantly correlated with total UPDRS score in patients with PD (r = -0.35, P = 0.08). Moreover, patients with PD with Hoehn and Yahr scale score ≥ 2 had a lower NAA/Cr level in SN compared to patients with a lower stage. Conclusion: This study shows that 1.5 tesla proton MRS is unable to detect metabolite abnormalities in patients with PD who are under treatment. However, the NAA/Cr ratio in the SN might be a useful imaging biomarker for evaluation of disease severity in these patients.

Longitudinal Monitoring of Microstructural Alterations in Cerebral Ischemia with in Vivo Diffusion-weighted MR Spectroscopy.

Background The time course of cellular damage after acute ischemic stroke (IS) is currently not well known, and specific noninvasive markers of microstructural alterations linked to inflammation are lacking, which hinders the monitoring of anti-inflammatory treatment. Purpose To evaluate the temporal pattern of neuronal and glial microstructural changes after stroke using in vivo single-voxel diffusion-weighted MR spectroscopy. Materials and Methods In this prospective longitudinal study, participants with IS and healthy volunteers (HVs) underwent MRI at 3.0 T. In participants with IS, apparent diffusion coefficients (ADCs) and concentrations of total N-acetyl-aspartate (tNAA), total creatine (tCr), and total choline (tCho) were measured in volumes of interest (VOIs), including the lesion VOI (VOIles) and the contralateral VOI (VOIcl) at 2 weeks, 1 month, and 3 months after IS. HVs were examined once, with VOIs located in the same brain regions as participants with IS. Within- and between-group differences and longitudinal changes were examined using linear mixed-effects models. Results Twenty participants with IS (mean age, 61 years ± 13 [SD]; 12 women) and 20 HVs (mean age, 59 years ± 13; 12 women) were evaluated. No differences in ADCs or concentrations were observed in VOIcl between HVs and participants with IS. In participants with IS, the ADC of tCr was higher in VOIles than in VOIcl at 1 month (+14.4%, P = .004) and 3 months after IS (+19.0%, P < .001), while the ADC of tCho was higher only at 1 month (+16.7%, P = .001). No difference in the ADC of tNAA was observed between the two VOIs at any time point. tNAA and tCr concentrations were lower in VOIles than in VOIcl and were stable over time (approximately -50% and -30%, respectively; P < .001). Conclusion High diffusivity of choline-containing compounds and total creatine (tCr) in the ischemic lesion 1 month after ischemic stroke (IS) indicates glial morphologic changes, suggesting that active inflammation is still ongoing at this time point. High tCr diffusivity up to 3 months after IS likely reflects the presence of astrogliosis at the chronic stage of cerebral ischemia. Clinical trial registration no. NCT02833961 © RSNA, 2022 Online supplemental material is available for this article.

Effect of high-intensity interval training on hippocampal metabolism in older adolescents

Introduction: Accumulating evidence supports the benefits of physical activity and fitness for young people’s cognitive function. Although well-evidenced in older adults, the effects of exercise on the hippocampus in youth is relatively unknown. This study examined the impact of a 6-month school-based physical activity intervention involving high-intensity interval training (Burn 2 Learn [B2L]) on hippocampal metabolism in adolescents using magnetic resonance spectroscopy (MRS). We hypothesized that the B2L intervention would increase concentrations of N-acetylaspartate (NAA), glutamate+glutamine (Glx), total Creatine and total Choline, and decrease concentrations of Myo-inositol.

Is dietary choline intake related to dementia and Alzheimer’s disease risks? Results from the Framingham Heart Study

The positive association of choline for cognition has been reported in both animal and human studies, yet the associations of choline with the risks of incident dementia or Alzheimer's disease (AD) in humans is unclear. Our objective was to test the hypothesis that lower or higher dietary choline intake is associated with increased or decreased, respectively, risks of incident dementia and AD. Data from the Framingham Heart Study Offspring Cohort exam 5 to exam 9 were used. Participants were free of dementia and stroke, with a valid self-reported 126-item Harvard FFQ at exam 5. The intakes of total choline, its contributing compounds, and betaine were estimated based on a published nutrient database. The intakes were updated at each exam to represent the cumulative average intake across the 5 exams. The associations between dietary choline intakes and incident dementia and AD were examined in mixed-effect Cox proportional hazard models, adjusting for covariates. A total of 3224 participants (53.8% female; mean ± SD age, 54.5 ± 9.7 y) were followed up for a mean ± SD of 16.1 ± 5.1 y (1991-2011). There were 247 incident dementia cases, of which 177 were AD. Dietary choline intake showed nonlinear relationships with incident dementia and AD. After adjusting for covariates, low choline intake (defined as ≤ 219 and ≤ 215 mg/d for dementia and AD, respectively) was significantly associated with incident dementia and incident AD. Low choline intake was associated with increased risks of incident dementia and AD.

Elevated GABA level in the precuneus and its association with pain intensity in patients with postherpetic neuralgia: An initial proton magnetic resonance spectroscopy study

PurposeThis study aimed to explore the changes in gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, and their correlations with clinical indicators in patients with postherpetic neuralgia (PHN). MethodsA totally of 22 PHN patients and 21 sex-, age-, and education-matched healthy controls (HCs) underwent proton magnetic resonance spectroscopy scanning. The spectral data of GABA in the precuneus was obtained by Mescher-Garwood point-resolved spectroscopy, whereas the spectral data of Glu, total N-acetyl-l-aspartic acid (tNAA) and total choline (tCho) were obtained by point-resolved spectroscopy. The pain intensity of PHN was assessed by numeric rating scales (NRS). The edited GABA signal was displayed as GABA+ due to overlapping macromolecules and homocarnosine signals. Total creatine (tCr) level in individual was used as an endogenous reference. The neurometabolites levels of PHN patients were compared with those of healthy individuals and the correlations with clinical variables (pain duration and intensity) were analyzed. ResultsPHN patients had higher GABA+/tCr levels in the precuneus than HCs (P = 0.009), with no significant differences in the levels of Glu/ tCr, tNAA/ tCr and tCho/ tCr (all P > 0.05). The GABA+/ tCr levels were positively correlated with the NRS scores of the PHN patients (r = 0.473, P = 0.030). ConclusionIncreased GABA+/tCr levels in the precuneus and their association with pain intensity of PHN patients suggested a key role of the abnormalities of regional GABAergic neurons in the pathophysiological mechanisms of pain in PHN.

One-carbon metabolism-related nutrients intake is associated with lower risk of preeclampsia in pregnant women: a matched case-control study

Many studies have suggested that folate plays a role in preeclampsia (PE) risks, but few studies have assessed folate-related 1-carbon metabolism (OCM)-related nutrients with the risk of PE. We hypothesized that OCM-related nutrients are associated with PE. A 1:1 matched case-control study was conducted to explore the association between dietary OCM-related nutrients intake and the risk of PE in pregnant Chinese women. Four hundred and forty pairs of pregnant women with PE and hospital-based, healthy pregnant women, matched according to gestational week (±1 week) and age (±3 years), were recruited. Dietary intake was assessed using a validated 78-item semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. Restricted cubic splines were plotted to evaluate the dose-response relationship between dietary OCM-related nutrient intake and the risk of PE. Intake of folate, vitamin B6, vitamin B12, methionine, and total choline were inversely related to the risk of PE after adjustment for covariates (all P trend < .05). Adjusted ORs (95% CIs) for quartile 4 versus quartile 1 were 0.71 (0.55-0.93) for folate, 0.66 (0.50-0.87) for vitamin B6, 0.68 (0.52-0.88) for vitamin B12, 0.77 (0.60-0.81) for methionine, and 0.67 (0.51-0.87) for total choline. This study suggests that dietary OCM-related nutrients intake is associated with lower odds of PE in pregnant Chinese women.

Longitudinal evaluation of proton magnetic resonance spectroscopy metabolites as biomarkers in Huntington's disease.

Proton magnetic resonance spectroscopy is a non-invasive method of exploring cerebral metabolism. In Huntington's disease, altered proton magnetic resonance spectroscopy-determined concentrations of several metabolites have been described; however, findings are often discrepant and longitudinal studies are lacking. Proton magnetic resonance spectroscopy metabolites may represent a source of biomarkers, thus their relationship with established markers of disease progression require further exploration to assess prognostic value and elucidate pathways associated with neurodegeneration. In a prospective single-site controlled cohort study with standardized collection of CSF, blood, phenotypic and volumetric imaging data, we used 3 T proton magnetic resonance spectroscopy in conjunction with the linear combination of model spectra method to quantify seven metabolites (total n-acetylaspartate, total creatine, total choline, myo-inositol, GABA, glutamate and glutathione) in the putamen of 59 participants at baseline (15 healthy controls, 15 premanifest and 29 manifest Huntington's disease gene expansion carriers) and 48 participants at 2-year follow-up (12 healthy controls, 13 premanifest and 23 manifest Huntington's disease gene expansion carriers). Intergroup differences in concentration and associations with CSF and plasma biomarkers; including neurofilament light chain and mutant Huntingtin, volumetric imaging markers; namely whole brain, caudate, grey matter and white matter volume, measures of disease progression and cognitive decline, were assessed cross-sectionally using generalized linear models and partial correlation. We report no significant groupwise differences in metabolite concentration at baseline but found total creatine and total n-acetylaspartate to be significantly reduced in manifest compared with premanifest participants at follow-up. Additionally, total creatine and myo-inositol displayed significant associations with reduced caudate volume across both time points in gene expansion carriers. Although relationships were observed between proton magnetic resonance spectroscopy metabolites and biofluid measures, these were not consistent across time points. To further assess prognostic value, we examined whether baseline proton magnetic resonance spectroscopy values, or rate of change, predicted subsequent change in established measures of disease progression. Several associations were found but were inconsistent across known indicators of disease progression. Finally, longitudinal mixed-effects models revealed glutamine + glutamate to display a slow linear decrease over time in gene expansion carriers. Altogether, our findings show some evidence of reduced total n-acetylaspartate and total creatine as the disease progresses and cross-sectional associations between select metabolites, namely total creatine and myo-inositol, and markers of disease progression, potentially highlighting the proposed roles of neuroinflammation and metabolic dysfunction in disease pathogenesis. However, the absence of consistent group differences, inconsistency between baseline and follow-up, and lack of clear longitudinal change suggests that proton magnetic resonance spectroscopy metabolites have limited potential as Huntington's disease biomarkers.

Association between dietary intake of one-carbon metabolism nutrients and hyperglycemia in coal-burning fluorosis areas of Guizhou, China.

Background and aimsThere are limited studies describing the association between dietary intake of one-carbon metabolism nutrients and hyperglycemia. The present study aimed to investigate the association of habitual dietary intake of one-carbon metabolism nutrients with hyperglycemia in a fluorosis area in China, and explored the interaction between these nutrients and fluorosis related to hyperglycemia.MethodIn a cross-sectional study, we recruited 901 villagers, ages ranging from 18–75, in Guizhou Province. Dietary data and other covariate data were obtained through an interviewer-administered questionnaire. We collected venous blood samples from participants who had fasted for one night to obtain fasting blood glucose levels and we categorized dietary intake of betaine, total choline, methionine, folate, vitamins B6 and B12, and choline subclasses into quartiles (Q1–Q4). The lowest quartile (Q1) served as the reference group. An unconditional logistic regression model was used to evaluate the protective effects of a dietary intake of one-carbon nutrients against hyperglycemia. We calculated Odds Ratios (ORs) with 95% confidence intervals (CIs). A presence or absence of fluorosis subgroup analysis was performed to determine the potential effect of fluorosis on hyperglycemia.ResultAfter adjusting for potential confounding factors, we found that a greater intake of dietary vitamin B6, total choline and methyl-donor index was inversely associated with the occurrence of hyperglycemia (P-trend <0.05). However, there were no significant associations between hyperglycemia and the dietary intake of folate, vitamin B12, methionine, and betaine. As for the choline subgroups, it showed that the dietary intake of free choline, phosphatidylcholine, and glycerol phosphatidylcholine was negatively correlated with the occurrence of hyperglycemia (P < 0.05). In contrast, there was no statistical association between dietary phosphatidylcholine and sphingomyelin and hyperglycemia (all P > 0.05). The results of subgroup analysis showed that dietary intake of folate, vitamin B6, total choline, free choline, glycerol phosphorylcholine, and phosphocholine had a protective effect against the occurrence of hyperglycemia in the non-fluorosis subgroup, although no effects were observed in the fluorosis subgroup. There were significant interactions between these nutrients and fluorosis (P = 0.010–0.048).ConclusionThe study demonstrated that higher dietary intake of vitamin B6, total choline, methyl-donor index, free choline, glycerol phosphorylcholine, and phosphocholine in choline compounds were associated with a lower incidence of hyperglycemia. Moreover, the associations were modified by the presence or absence of fluorosis. Further investigation is needed to test the association in large-scale follow-up studies.

The contribution of the 1H-MRS lipid signal to cervical cancer prognosis: a preliminary study

BackgroundThe aim of this study was to investigate the role of the lipid peak derived from 1H magnetic resonance (MR) spectroscopy in assessing cervical cancer prognosis, particularly in assessing response to neoadjuvant chemotherapy (NACT) of locally advanced cervical cancer (LACC).MethodsWe enrolled 17 patients with histologically proven cervical cancer who underwent 3-T MR imaging at baseline. In addition to conventional imaging sequences for pelvic assessment, the protocol included a single-voxel point-resolved spectroscopy (PRESS) sequence, with repetition time of 1,500 ms and echo times of 28 and 144 ms. Spectra were analysed using the LCModel fitting routine, thus extracting multiple metabolites, including lipids (Lip) and total choline (tCho). Patients with LACC were treated with NACT and reassessed by MRI at term. Based on tumour volume reduction, patients were classified as good responder (GR; tumour volume reduction > 50%) and poor responder or nonresponder (PR-or-NR; tumour volume reduction ≤ 50%).ResultsOf 17 patients, 11 were LACC. Of these 11, only 6 had both completed NACT and had good-quality 1H-MR spectra; 3 GR and 3 PR-or-NR. A significant difference in lipid values was observed in the two groups of patients, particularly with higher Lip values and higher Lip/tCho ratio in PR-NR patients (p =0.040). A significant difference was also observed in choline distribution (tCho), with higher values in GR patients (p = 0.040).ConclusionsAssessment of lipid peak at 1H-MR spectroscopy could be an additional quantitative parameter in predicting the response to NACT in patients with LACC.

The Role of [18F]F-Choline PET/CT in the Initial Management and Outcome Prediction of Prostate Cancer: A Real-World Experience from a Multidisciplinary Approach.

Initial staging of prostate cancer (PCa) is usually performed with conventional imaging (CI), involving computed tomography (CT) and bone scanning (BS). The aim of this study was to analyze the role of [18F]F-choline positron emission tomography (PET)/CT in the initial management and outcome prediction of PCa patients by analyzing data from a multidisciplinary approach. We retrospectively analyzed 82 patients who were discussed by the uro-oncology board of the University Hospital of Ferrara for primary staging newly diagnosed PCa (median age 72 (56–86) years; median baseline prostate specific antigen (PSA) equal to 8.73 ng/mL). Patients were divided into three groups based on the imaging performed: group A = only CI; group B = CI + [18F]F-choline PET/CT; group C = only [18F]F-choline PET/CT. All data on imaging findings, therapy decisions and patient outcomes were retrieved from hospital information systems. Moreover, we performed a sub-analysis of semiquantitative parameters extracted from [18F]F-choline PET/CT to search any correlation with patient outcomes. The number of patients included in each group was 35, 35 and 12, respectively. Patients with higher values of initial PSA were subjected to CI + PET/CT (p = 0.005). Moreover, the use of [18F]F-choline PET/CT was more frequent in patients with higher Gleason score (GS) or ISUP grade (p = 0.013). The type of treatment performed (surgery n = 33; radiation therapy n = 22; surveillance n = 6; multimodality therapy n = 6; systemic therapy n = 13; not available n = 2) did not show any relationship with the modality adopted to stage the disease. [18F]F-choline PET/CT induced a change of planned therapy in 5/35 patients in group B (14.3%). Moreover, patients investigated with [18F]F-choline PET/CT alone demonstrated longer biochemical recurrence (BCR)-free survival (30.8 months) in comparison to patients of groups A and B (15.5 and 23.5 months, respectively, p = 0.006), probably due to a more accurate selection of primary treatment. Finally, total lesion choline kinase activity (TLCKA) of the primary lesion, calculated by multiplying metabolic tumor volume and mean standardized uptake value (SUVmean), was able to more effectively discriminate patients who had recurrence after therapy compared to those without (p = 0.03). In our real-world experience [18F]F-choline PET/CT as a tool for the initial management of PCa had a relevant impact in terms of therapy selection and was associated with longer BCR-free survival. Moreover, TLCKA of the primary lesion looks a promising parameter for predicting recurrence after curative therapy.