Neurofilament light level correlates with brain atrophy, and cognitive and motor performance

Peer reviewe

Synergistic associations of cognitive and motor impairments with functional outcome in covert cerebral small vessel disease

Background Cognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their combined effects on functional outcome have not been elucidated. This study investigated the interactions and mediating effects of cognitive and motor functions on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH). Methods Participants of the Helsinki Small Vessel Disease Study (n = 152) were assessed according to an extensive clinical, physical, neuropsychological and MRI protocol. Volumes of WMH and gray matter (GM) were obtained with automated segmentation. Results Cognitive (global cognition, executive functions, processing speed, memory) and motor functions (gait speed, single-leg stance, timed up-and-go) had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on informant-evaluated IADL, but not on self-evaluated quality of life. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up-and-go performance. Conclusion The results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than their individual effects. Patients with both impairments are at disproportionate risk for poor outcome. WMH and brain atrophy contribute to disability through cognitive and motor impairment.Peer reviewe

Protocol for motor and language mapping by navigated TMS in patients and healthy volunteers; workshop report

Navigated transcranial magnetic stimulation (nTMS) is increasingly used for preoperative mapping of motor function, and clinical evidence for its benefit for brain tumor patients is accumulating. In respect to language mapping with repetitive nTMS, literature reports have yielded variable results, and it is currently not routinely performed for presurgical language localization. The aim of this project is to define a common protocol for nTMS motor and language mapping to standardize its neurosurgical application and increase its clinical value. The nTMS workshop group, consisting of highly experienced nTMS users with experience of more than 1500 preoperative nTMS examinations, met in Helsinki in January 2016 for thorough discussions of current evidence and personal experiences with the goal to recommend a standardized protocol for neurosurgical applications. nTMS motor mapping is a reliable and clinically validated tool to identify functional areas belonging to both normal and lesioned primary motor cortex. In contrast, this is less clear for language-eloquent cortical areas identified by nTMS. The user group agreed on a core protocol, which enables comparison of results between centers and has an excellent safety profile. Recommendations for nTMS motor and language mapping protocols and their optimal clinical integration are presented here. At present, the expert panel recommends nTMS motor mapping in routine neurosurgical practice, as it has a sufficient level of evidence supporting its reliability. The panel recommends that nTMS language mapping be used in the framework of clinical studies to continue refinement of its protocol and increase reliability.Peer reviewe

Results from the CERN pilot CLOUD experiment

During a 4-week run in October–November 2006, a pilot experiment was performed at the CERN Proton Synchrotron in preparation for the Cosmics Leaving OUtdoor Droplets (CLOUD) experiment, whose aim is to study the possible influence of cosmic rays on clouds. The purpose of the pilot experiment was firstly to carry out exploratory measurements of the effect of ionising particle radiation on aerosol formation from trace H2SO4 vapour and secondly to provide technical input for the CLOUD design. A total of 44 nucleation bursts were produced and recorded, with formation rates of particles above the 3 nm detection threshold of between 0.1 and 100 cm -3 s -1, and growth rates between 2 and 37 nm h -1. The corresponding H2O concentrations were typically around 106 cm -3 or less. The experimentally-measured formation rates and htwosofour concentrations are comparable to those found in the atmosphere, supporting the idea that sulphuric acid is involved in the nucleation of atmospheric aerosols. However, sulphuric acid alone is not able to explain the observed rapid growth rates, which suggests the presence of additional trace vapours in the aerosol chamber, whose identity is unknown. By analysing the charged fraction, a few of the aerosol bursts appear to have a contribution from ion-induced nucleation and ion-ion recombination to form neutral clusters. Some indications were also found for the accelerator beam timing and intensity to influence the aerosol particle formation rate at the highest experimental SO2 concentrations of 6 ppb, although none was found at lower concentrations. Overall, the exploratory measurements provide suggestive evidence for ion-induced nucleation or ion-ion recombination as sources of aerosol particles. However in order to quantify the conditions under which ion processes become significant, improvements are needed in controlling the experimental variables and in the reproducibility of the experiments. Finally, concerning technical aspects, the most important lessons for the CLOUD design include the stringent requirement of internal cleanliness of the aerosol chamber, as well as maintenance of extremely stable temperatures (variations below 0.1 °C

Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes

The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward β cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic and permanently autoantibody negative. Individuals who developed diabetes had reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth, reduced levels of triglycerides and antioxidant ether phospholipids throughout the follow up, and increased levels of proinflammatory lysoPCs several months before seroconversion to autoantibody positivity. The lipid changes were not attributable to HLA-associated genetic risk. The appearance of insulin and glutamic acid decarboxylase autoantibodies was preceded by diminished ketoleucine and elevated glutamic acid. The metabolic profile was partially normalized after the seroconversion. Autoimmunity may thus be a relatively late response to the early metabolic disturbances. Recognition of these preautoimmune alterations may aid in studies of disease pathogenesis and may open a time window for novel type 1 diabetes prevention strategies

The FADS1 rs174550 Genotype Modifies the n-3 and n-6 PUFA and Lipid Mediator Responses to a High Alpha-Linolenic Acid and High Linoleic Acid Diets

Scope: The fatty acid composition of plasma lipids, which is associated with biomarkers and risk of non-communicable diseases, is regulated by dietary polyunsaturated fatty acids (PUFAs) and variants of fatty acid desaturase (FADS). We investigated the interactions between dietary PUFAs and FADS1 rs174550 variant.Methods and results: Participants (n = 118), homozygous for FADS1 rs174550 variant (TT and CC) followed a high alpha-linolenic acid (ALA, 5 percent of energy (E-%)) or a high linoleic acid (LA, 10 E-%) diet during an 8-week randomized controlled intervention. Fatty acid composition of plasma lipids and PUFA-derived lipid mediators were quantified by gas and liquid chromatography mass spectrometry, respectively. The high-LA diet increased the concentration of plasma LA, but not its lipid mediators. The concentration of plasma arachidonic acid decreased in carriers of CC and remained unchanged in the TT genotype. The high-ALA diet increased the concentration of plasma ALA and its cytochrome P450-derived epoxides and dihydroxys, and cyclooxygenase-derived monohydroxys. Concentrations of plasma eicosapentaenoic acid and its mono- and dihydroxys increased only in TT genotype carriers.Conclusions: These findings suggest the potential for genotype-based recommendations for PUFA consumption, resulting in modulation of bioactive lipid mediators which can exert beneficial effects in maintaining health.</p

Global burden of small vessel disease-related brain changes on MRI predicts cognitive and functional decline

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (PPeer reviewe

Serum Lipidomics Meets Cardiac Magnetic Resonance Imaging: Profiling of Subjects at Risk of Dilated Cardiomyopathy

Peer reviewe

Triacylglycerol Fatty Acid Composition in Diet-Induced Weight Loss in Subjects with Abnormal Glucose Metabolism – the GENOBIN Study

BACKGROUND: The effect of weight loss on different plasma lipid subclasses at the molecular level is unknown. The aim of this study was to examine whether a diet-induced weight reduction result in changes in the extended plasma lipid profiles (lipidome) in subjects with features of metabolic syndrome in a 33-week intervention. METHODOLOGY/PRINCIPAL FINDINGS: Plasma samples of 9 subjects in the weight reduction group and 10 subjects in the control group were analyzed using mass spectrometry based lipidomic and fatty acid analyses. Body weight decreased in the weight reduction group by 7.8+/-2.9% (p<0.01). Most of the serum triacylglycerols and phosphatidylcholines were reduced. The decrease in triacylglycerols affected predominantly the saturated short chain fatty acids. This decrease of saturated short chain fatty acid containing triacylglycerols correlated with the increase of insulin sensitivity. However, levels of several longer chain fatty acids, including arachidonic and docosahexanoic acid, were not affected by weight loss. Levels of other lipids known to be associated with obesity such as sphingolipids and lysophosphatidylcholines were not altered by weight reduction. CONCLUSIONS/SIGNIFICANCE: Diet-induced weight loss caused significant changes in global lipid profiles in subjects with abnormal glucose metabolism. The observed changes may affect insulin sensitivity and glucose metabolism in these subjects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00621205

Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies

Funder: Dutch Scientific OrganizationFunder: Foundation Plan AlzheimerFunder: Icelandic Heart AssociationFunder: Academy of FinlandFunder: VicHealth and Cancer Council VictoriaFunder: Juselius FoundationFunder: Uppsala University Hospital and the Swedish Research Council for Health, Working Life and WelfareFunder: the Institut National de la Sante et de la Recherche MedicaleFunder: , the University Bordeaux 2 Victor SegalenFunder: Sanofi; funder-id: http://dx.doi.org/10.13039/100004339Funder: Fondation pour la Recherche Medicale, the Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, MGEN, Institut de la Longevite, Conseils Regionaux d’Aquitaine et Bourgogne, Fondation de France, Ministry of Research–Institut National de la Sante and de la Recherche Medicale Programme CohortesFunder: Caisse Nationale pour la Solidarite et l’AutonomieFunder: Swedish Research Council for Health, Working Life and Welfare, Uppsala City Council, Swedish Research Council, and Swedish Diabetes FoundationBackground: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). Methods and findings: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors. Conclusions: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D