Search

Stephanie Bolton,1 Rachel Gair,2 Lars-Göran Nilsson,3 Michael Matthews,1 Louanne Stewart,1 Natasha McCullagh1 1Renal Unit, Antrim Area Hospital, Northern Health and Social Care Trust, Northern Ireland, UK; 2UK Renal Registry, Bristol, UK; 3Baxter International Inc., Lund, SwedenCorrespondence: Stephanie BoltonRenal Unit, Antrim Area Hospital, Northern Health and Social Care Trust, Northern Ireland, UKEmail Stephanie.Bolton@northerntrust.hscni.netIntroduction: Most people on hemodialysis (HD) report a high symptom burden. Fatigue and lack of energy are prominent, interfering with daily life and associated with poor outcome. Prolonged recovery time after each of the thrice weekly dialysis treatments is common. The impact of HD therapies, like expanded hemodialysis (HDx), on patient reported recovery time and symptom burden is unclear.Methods: A dialysis unit decided to perform regular assessments of patient-reported symptom burden, using the POS-S Renal Symptom questionnaire and the “Recovery time from last dialysis session” question as part of routine patient focused care. At a similar time, a clinical evidence-based decision was taken to switch the in-center dialysis cohort from regular high-flux dialysis membrane to medium cut-off (MCO) membrane, introducing HDx therapy.Results: Quarterly assessment of patient-reported symptom burden was well accepted. A sustained clinically relevant reduction in post-dialysis recovery time was observed following the therapy switch. In patients providing data up to 12 months (N = 58), median recovery time decreased from 210 min (IQR 7.5– 600) to 60 min (0– 210; p = 0.002) and 105 min (0– 180; p = 0.001) at 6 and 12 months, respectively. Thirty-six percent of individuals reported a recovery time longer than 360 minutes at the initial assessment, which decreased to 9% at 12 months. The POS-S Renal total symptom score showed a decrease at 6 months but no difference from baseline at 12 months. The “fatigue/lack of energy” symptom showed a sustained improvement; the percentage of participants scoring its impact as “severe” or “overwhelming” decreased from 28% at baseline to 16% at 12 months. Changes in other symptoms were more variable.Conclusion: Regular assessment of patient reported symptoms is feasible in routine dialysis practice and can help in evaluating the impact of clinical interventions. Observations suggest that HDx therapy may reduce post-dialysis recovery time and improve perceived fatigue level.Keywords: post-dialysis recovery time, symptom burden, fatigue, HDx therapy

Expanded hemodialysis (HDx) provides increased clearance of conventional and large middle molecules through innovative medium cutoff (MCO) membranes. However, there is a paucity of real‐world data regarding the benefits and safety of HDx. This large observational study evaluated outcomes among patients in Colombia undergoing HDx at a extended dialysis clinical services provider. This was a prospective single cohort study of prevalent patients who were treated with HDx; baseline information was collected from the most recent data before patients were started on HDx. Patients were followed prospectively for 1 year for changes in serum albumin and other laboratory parameters compared with the baseline. Survival, hospitalization and safety were assessed from the start of HDx. A total of 1000 patients were invited to enroll; 992 patients met the inclusion criteria for data analysis and 638 patients completed the year of follow‐up. Seventy‐four (8%) patients died during 866 patient‐years (PY) of follow‐up; the mortality rate was 8.54 deaths/100 PY (95% confidence interval [CI], 6.8‐10.7). There were 673 hospitalization events with a rate of 0.79 events/PY (95% CI, 0.73‐0.85) with 6.91 hospital days/PY (95% CI, 6.74‐7.09). The observed variability from baseline and maximum average change in mean serum albumin levels were −1.8% and −3.5%, respectively. No adverse events were related to the MCO membrane. HDx using an MCO membrane maintains stable serum albumin levels and is safe in terms of nonoccurrence of dialyzer related adverse events.

First published online: January 2020 Growth models (GM) of the mixed-effects and latent curve varieties have become popular methodological tools in lifespan research. One of the major advantages of GM is their flexibility in studying individual differences in change. We scrutinized the change functions of GM used in five years of publications on cognitive aging. Of the 162 publications that we identified, 88% test linear or quadratic polynomials, and fewer than 5% apply functions that are nonlinear in their parameters, such as exponential decline. This apparent bias in favor of polynomial decomposition calls for exploring what conclusions about individual differences in change are likely to be drawn if one applies linear or quadratic GMs to data simulated under a conceptually and empirically plausible model of exponential cognitive decline from adulthood to old age. Hence, we set up a simulation that manipulated the rate of exponential decline, measurement reliability, number of occasions, interval width, and sample size. True rate of decline and interval width influenced results strongly, number of occasions and measurement reliability exerted a moderate effect, and the effects of sample size appeared relatively minor. Critically, our results show that fit statistics generally do not differentiate misspecified linear or quadratic models from the true exponential model. Moreover, power to detect variance in change for the linear and quadratic GMs is low, and estimates of individual differences in level and change can be highly biased by model misspecification. We encourage researchers to also consider plausible nonlinear change functions when studying behavioral development across the lifespan.

Expanded hemodialysis (HDx), using medium cut-off membrane, is a novel therapy that effectively clears middle molecules (MMs). We aimed to compare HDx to hemodiafiltration (HDF) in an open randomized clinical study. Patients currently on HDF (age 18-80 years; on HDF >3 months) were randomized to switch to HDx (N = 21) or continue HDF (N = 22) with a 24-week follow-up. Pre- to post-dialysis reduction ratios (RR) and changes in pre-dialysis levels over time were evaluated for MMs and clinical biomarkers. Use of erythropoiesis-stimulating agents (ESAs) was assessed. HDx showed greater RR for YKL-40 while RR appeared similar between groups for beta2 -microglobulin, FGF-23, and free light chains. Intradialytic changes in inflammatory biomarkers (IL-6, CRP, PTX3) did not differ between therapies. Changes from baseline to 12 and 24 weeks did not differ between groups for MMs, inflammatory markers, albumin, fibrinogen, hemoglobin, PTH, and phosphorus. Use of ESAs tended to decrease in HDx arm while remaining stable in HDF arm. HDx appeared safe with similar clinical effectiveness as HDF. With fewer requirements and resource needs, HDx provides an attractive alternative to HDF.

The second most common biological complication in fixed prosthodontics is loss of pulp vitality, which may lead to restoration loss. While reasons for loss of pulp vitality are unclear, 2 potential contributing factors, duration of the interim restoration and operator experience, have not been fully investigated.The purpose of this retrospective study was to investigate whether the duration of the interim restoration or the experience of the dentist was correlated with loss of pulp vitality.Fixed prosthetic restorations placed between 2005 and 2012 were retrospectively analyzed. Abutment teeth supporting single-unti or multiunit restorations were evaluated regarding loss of pulp vitality. The Mann-Whitney U test and simple logistic regression were used, with α=.05 for the subsequent multiple logistic regression. The experience of dental professionals was defined by the number of treatments performed and coupled with failure rate by using an analysis of variance.One hundred seventy-four dentists made 15 879 restorations, of which 1136 failed during the observation period, a failure rate of 7.2%. Two hundred fifty restorations were randomly selected from the failed restorations, and a corresponding 250 restorations were randomly selected from nonfailed restorations for the control group. Increased duration with interim replacement was linked to a higher risk of loss of pulp vitality (P.001). Failure rate in the dentist group varied from 0% to 100%. No significant differences in failure rate were found among dentists who did few restorations and those who performed larger numbers of restorations.The results of the present study suggest that operator experience does not affect failure rate. However, extended time with an interim restoration was a contributing factor to the loss of pulp vitality.

Background and Aims HDx is a dialysis therapy that uses dialyzers with newly designed medium cut-off membranes (MCOs), which show a greater capacity for purification of middle molecules than conventional dialyzers and requires less technical resources than OL-HDF. However, it is not well known if HDx has comparable clinical results with OL-HDF. Therefore, the aim of this study was to evaluate the clinical differences between patients dialyzed with HDx and OL-HDF. Method A 24-week prospective study that included 43 patients between 18 and 80 years old, in OL-HDF at least 3 months before the start of the study, stratified by residual function; and randomized for HDx or HDF-OL therapy. Twenty-one patients assigned to HDx used the Theranova® 500 dialyzer with MCO membrane; and 22 patients with HDF-OL with Polyflux® 170H dialyzer. Variables related to dialysis were analyzed: blood flow rate (Qb), ultrafiltration volume (VUF), dialysis time, Kt/V, and complications; anemia [Hemoglobin (Hb), transferrin saturation (TSAT), Ferritin, erythropoietin stimulating agent (ESA) dosage (IU/week), erythropoietin resistance index (ERI), iron dose]; the bone mineral metabolism [calcium (Ca), phosphorus (Pi), product CaxPi, Paratohormone (PTH), fibroblast growth factor 23 (FGF-23)]; and healthcare resource utilization (hospitalization, cardiovascular events, infectious events and death). Results The substitution volume in the OL-HDF group was 24.4±3.2 liters. No significant differences were found in time of treatment, QB, residual diuresis or VUF. The Kt/V was similar in both groups HDx: 1.8±0.26; OL-HDF: 1.8±0.28. No significant differences in the number of adverse events during hemodialysis between the two groups. No differences in the levels of P, Ca, PTH between both groups. However, there were differences in FGF-23 at week 12 compared to baseline (HDx: -188±1351 pg/mL; OL-HDF: +218±1293 pg/mL, p=0.48). The iron dose showed no significant differences between both groups. The use of ESA was lower in the HDx group at the end of the study (HDx: 5605±7115 IU/Week; OL-HDF: 7667±5867 IU/Week), maintaining hemoglobin values stable throughout the study in both treatment groups (HDx: 11.2±1; OL-HDF: 11.7±0.8 g/dl at 24-week). Serum TSAT was comparable between the groups at all timepoints in the study. Serum ferritin levels were slightly higher in HDx group and showed an overall increase at Week 24. Both treatments were effective in maintaining pre-dialysis albumin levels. At 12 weeks (HDx: 0.06±0.47; OL-HDF: -0.01±0.26, p=0.889) and 24 weeks of treatment (HDx: -0.02±0.25; OL-HDF: - 0.02±0.34, p=0.5948) versus baseline. The assessment of rates of hospitalizations, cardiovascular events, infective episodes and death showed no substantial differences between both groups. Conclusion In our experience, HDx with Theranova® 500 is a safe and effective hemodialysis technique. A short-term HDx therapy decreases FGF23 levels and the needs of EPO compared to OL-HDF. Both techniques are similar in the other parameters analysed.

Background and Aims Expanded hemodialysis (HDx) with a medium cut-off dialyzer, Theranova® 500, can achieve a middle molecule clearance but its efficacy or comparison with HDF is still unknown. It is still unknown on how large middle molecules and inflammation markers are affected over time with a medium cut-off dialyzer. This study compared the purifying effectiveness of Theranova® 500 dialyzer with respect to online Hemodiafiltration (OL-HDF). Method Sixty-three patients who were already receiving HDF were evaluated and 43 were randomized by residual renal function. Twenty-one patients received treatment with HDx using Theranova® 500 and 22 patients remained in HDF in post-dilution mode, using a high-flux dialyzer, Polyflux® 170H, for up to 24 weeks. The dialysis time and the adequacy parameters for both arms were the same. Large middle molecules were measured (kappa immunoglobulin free light chains [κ-FLC], lambda immunoglobulin free light chains [λ-FLC], chitinase-3-like protein 1 [YKL-40], fibroblast growth factor 23 [FGF-23] and serum beta-2 microglobulin [β2M]), ; and inflammatory markers (high sensitivity C-reactive protein [hs-CRP], pentraxin - 3 [PTX-3], interleukin-6 [IL-6], interleukin-10 [IL-10]) at 12 weeks of treatment; and its change from baseline to weeks 12 and 24 in mid-week pre-dialysis. The method of measurement was the immunoassay. Siemens immunoassay was used for FLCs. Results HDx with Theranova® 500 demonstrated comparable results to OL-HDF with convective volume 24.4±3.2 L in terms of reduction rate (RR) of middle molecules (κ-FLC, λ-FLC, FGF-23 and β2M) at 12 weeks of treatment. HDx demonstrated similar performance to HDF in mid-week pre-dialysis plasma levels of middle molecules from baseline, at 12 and 24 weeks of treatment. Greater RR of YKL-40 at 12 weeks of treatment was seen in HDx group when compared to HDF (58.1% vs 42.4%; p≤0.0001), and there was a difference in the pre-dialysis β2M change from Baseline values between the groups (-0.60 for HDx arm and +3.28 for HDF arm, p=0.46). HDx with Theranova® 500 demonstrated comparable results to HDF in terms of reduction rate (RR) of inflammatory markers (hs-CRP, PTX-3, IL-6 and IL-10) at 12 weeks of treatment. There were no differences in the parameters of adequacy of dialysis between both arms. Both treatments were effective in maintaining pre-dialysis albumin and fibrinogen levels throughout the study. There were no significant adverse events related to the safety of Theranova. Conclusion HDx with Theranova® 500 is an emergent, effective and safe hemodialysis therapy that showed a purifying efficacy at least comparable to OL-HDF.

A process is described to assess the commutability of a reference material (RM) intended for use as a calibrator, trueness control, or external quality assessment sample based on the difference in bias between an RM and clinical samples (CSs) measured using 2 different measurement procedures (MPs). This difference in bias is compared with a criterion based on a medically relevant difference between an RM and CS results to make a conclusion regarding commutability. When more than 2 MPs are included, the commutability is assessed pairwise for all combinations of 2 MPs. This approach allows the same criterion to be used for all combinations of MPs included in the assessment. The assessment is based on an error model that allows estimation of various random and systematic sources of error, including those from sample-specific effects of interfering substances. An advantage of this approach is that the difference in bias between an RM and the average bias of CSs at the concentration (i.e., amount of substance present or quantity value) of the RM is determined and its uncertainty estimated. An RM is considered fit for purpose for those MPs for which commutability is demonstrated.

Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules.In two prospective, open-label, controlled, randomized, crossover pilot studies, 39 prevalent hemodialysis (HD) patients were studied in four dialysis treatments as follows: study 1, three MCO prototype dialyzers (AA, BB and CC with increasing permeability) and one high-flux dialyzer in HD; and study 2, two MCO prototype dialyzers (AA and BB) in HD and high-flux dialyzers in HD and hemodiafiltration (HDF). Primary outcome was lambda free light chain (λFLC) overall clearance. Secondary outcomes included overall clearances and pre-to-post-reduction ratios of middle and small molecules, and safety of MCO HD treatments.MCO HD provided greater λFLC overall clearance [least square mean (standard error)] as follows: study 1: MCO AA 8.5 (0.54), MCO BB 11.3 (0.51), MCO CC 15.0 (0.53) versus high-flux HD 3.6 (0.51) mL/min; study 2: MCO AA 10.0 (0.58), MCO BB 12.5 (0.57) versus high-flux HD 4.4 (0.57) and HDF 6.2 (0.58) mL/min. Differences between MCO and high-flux dialyzers were consistently significant in mixed model analysis (each P0.001). Reduction ratios of λFLC were greater for MCO. Clearances of α1-microglobulin, complement factor D, kappa FLC (κFLC) and myoglobin were generally greater with MCO than with high-flux HD and similar to or greater than clearances with HDF. Albumin loss was moderate with MCO, but greater than with high-flux HD and HDF.MCO HD removes a wide range of middle molecules more effectively than high-flux HD and even exceeds the performance of high-volume HDF for large solutes, particularly λFLC.

Background. Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules. Methods. In two prospective, open-label, controlled, randomized, crossover pilot studies, 39 prevalent hemodialysis (HD) patients were studied in four dialysis treatments as follows: study 1, three MCO prototype dialyzers (AA, BB and CC with increasing permeability) and one high-flux dialyzer in HD; and study 2, two MCO prototype dialyzers (AA and BB) in HD and high-flux dialyzers in HD and hemodiafiltration (HDF). Primary outcome was lambda free light chain (λFLC) overall clearance. Secondary outcomes included overall clearances and pre-to-post-reduction ratios of middle and small molecules, and safety of MCO HD treatments. Results. MCO HD provided greater λFLC overall clearance [least square mean (standard error)] as follows: study 1: MCO AA 8.5 (0.54), MCO BB 11.3 (0.51), MCO CC 15.0 (0.53) versus high-flux HD 3.6 (0.51) mL/min; study 2: MCO AA 10.0 (0.58), MCO BB 12.5 (0.57) versus high-flux HD 4.4 (0.57) and HDF 6.2 (0.58) mL/min. Differences between MCO and high-flux dialyzers were consistently significant in mixed model analysis (each P < 0.001). Reduction ratios of λFLC were greater for MCO. Clearances of α1-microglobulin, complement factor D, kappa FLC (κFLC) and myoglobin were generally greater with MCO than with high-flux HD and similar to or greater than clearances with HDF. Albumin loss was moderate with MCO, but greater than with high-flux HD and HDF. Conclusions. MCO HD removes a wide range of middle molecules more effectively than high-flux HD and even exceeds the performance of high-volume HDF for large solutes, particularly λFLC.

Objective Elevated cortisol levels with aging have been associated with atrophy of the hippocampus and prefrontal cortex (PFC), as well as with impaired cognitive functions in men. However, coexisting diseases have confounded many studies examining these relationships. Studies in women are lacking. Our objective was to test whether salivary cortisol levels were related to morphology of the hippocampus and the PFC, and to cognitive performance. Design A cross-sectional study including 200 elderly (55–80 years old) men and women. Method We used magnetic resonance imaging, tests of episodic-, semantic-, and working memory, visuospatial ability, and cortisol levels in four saliva samples collected during 1 day. Results Area under the curve (AUC) for cortisol levels was negatively related to cortical surface area of the left anterior cingulate gyrus (caudal PP=0.006), right lateral orbitofrontal cortex (P=0.004), and right rostral middle frontal gyrus (P=0.003). In women, there was also a negative relationship with cortical surface area in the left rostral middle frontal gyrus (P=0.006). No relationship was found between cortisol levels and hippocampal volume. Conclusion This study suggests that the structure of the medial PFC is related to cortisol levels in both elderly women and men.

Age-related differences in sensory functioning, processing speed, and working memory have been identified as three significant predictors of the age-related performance decline observed in complex ...

BACKGROUND We used a difference in bias approach to evaluate the commutability of 4 frozen serum pools for 8 direct methods for measurement of HDL and LDL cholesterol (HDLC and LDLC). METHODS Freshly collected nonfrozen sera from 138 diseased and 37 nondiseased patients and 4 frozen pools from the CDC Lipid Standardization Program were measured by direct methods and by the beta-quantification reference measurement procedure of the CDC. We used an error components model to estimate the difference in the bias component of error plus its uncertainty for frozen pools vs patient samples between the direct method and the reference procedure. Frozen pools with bias differences less than a critical value determined by either medical requirements for bias or the random error components of the measurement procedures were considered commutable. RESULTS On the basis of medical requirement criteria, 1 of the 4 frozen pools was commutable for most of the HDLC methods for both diseased and nondiseased patients, and none was commutable for LDLC methods. On the basis of random error criteria, all of the frozen pools were generally commutable for all of the HDLC methods for both diseased and nondiseased patients, and 1 of the 4 frozen pools was generally commutable for most of the LDLC methods for both diseased and nondiseased patients. CONCLUSIONS Commutability was assessed as the closeness of agreement of the difference in bias between a reference material and a set of patient samples. Criteria for commutability could be based on fixed medical requirements for bias or on random error components.

Background:The objective was to examine whether aspects of social relationships in old age are associated with all-cause dementia and Alzheimer's disease (AD).Methods:We studied 1,715 older adults (≥ 65 years) who were dementia-free at baseline over a period of up to 16 years. Data on living status, contact/visit frequency, satisfaction with contact frequency, and having/not having a close friend were analyzed using Cox proportional hazards regressions with all-cause dementia or AD as the dependent variable. To control for reverse causality and to identify potential long-term effects, we additionally performed analyses with delayed entry.Results:We identified 373 incident cases of dementia (207 with AD) during follow-up. The variable visiting/visits from friends was associated with reduced risk of all-cause dementia. Further, a higher value on the relationships index (sum of all variables) was associated with reduced risk of all-cause dementia and AD. However, in analyses with delayed entry, restricted to participants with a survival time of three years or more, none of the social relationship variables was associated with all-cause dementia or AD.Conclusions:The results indicate that certain aspects of social relationships are associated with incident dementia or AD, but also that these associations may reflect reverse causality. Future studies aimed at identifying other factors of a person's social life that may have the potential to postpone dementia should consider the effects of reverse causality.

Commutability is a property of a reference material (RM) that relates to the closeness of agreement between results for an RM and results for clinical samples (CSs) when measured by ≥2 measurement procedures (MPs). Commutability of RMs used in a calibration traceability scheme is an essential property for them to be fit for purpose. Similarly, commutability of trueness controls or external quality assessment samples is essential when those materials are used to assess trueness of results for CSs. This report is part 1 of a 3-part series describing how to assess commutability of RMs. Part 1 defines commutability and addresses critical components of the experimental design for commutability assessment, including selection of individual CSs, use of pooled CSs, qualification of MPs for inclusion, establishing criteria for the determination that an RM is commutable, generalization of commutability conclusions to future measurements made with the MPs included in the assessment, and information regarding commutability to be included in the certificate for an RM. Parts 2 and 3 in the series present 2 different statistical approaches to commutability assessment that use fixed criteria related to the medical decisions that will be made using the laboratory test results.

We compared weight, height, waist and hip circumferences (hip), body mass index (BMI), and waist-to-hip ratio in acute myocardial infarction (MI) patients and individually sex-and age-matched control subjects from the general population in the catchment area of the patients and predicted the risk of MI status by these basic anthropometric measures. The study cohort comprised 748 patients = 66 years). Risk of MI was assessed by conditional logistic regression. A narrow hip in men >66 years was the single strongest risk factor of MI among the anthropometric measures. The combination of hip and weight was particularly efficient in discriminating men >= 66 years with MI from their controls (area under the receiver operating characteristic (AUROC) curve = 0.82). In men = 66 years, the best discriminatory model contained only waist-to-hip ratio (AUROC = 0.67), whereas in women Corrigendum in: Journal of Obesity, Volume 2018, Article ID 3126805, https://doi.org/10.1155/2018/3126805

The dorsolateral pFC (DLPFC) is a key region for working memory. It has been proposed that the DLPFC is dynamically recruited depending on task demands. By this view, high DLPFC recruitment for low-demanding tasks along with weak DLPFC upregulation at higher task demands reflects low efficiency. Here, the fMRI BOLD signal during working memory maintenance and manipulation was examined in relation to aging and catechol-O-methyltransferase (COMT) Val158Met status in a large representative sample (n = 287). The efficiency hypothesis predicts a weaker DLPFC response during manipulation, along with a stronger response during maintenance for older adults and COMT Val carriers compared with younger adults and COMT Met carriers. Consistent with the hypothesis, younger adults and met carriers showed maximal DLPFC BOLD response during manipulation, whereas older adults and val carriers displayed elevated DLPFC responses during the less demanding maintenance condition. The observed inverted relations support a link between dopamine and DLPFC efficiency.

Human memory is a highly heritable polygenic trait with complex inheritance patterns. To study the genetics of memory and memory-related diseases, hippocampal functioning has served as an intermediate phenotype. The importance of investigating gene-gene effects on complex phenotypes has been emphasized, but most imaging studies still focus on single polymorphisms. APOE ε4 and BDNF Met, two of the most studied gene variants for variability in memory performance and neuropsychiatric disorders, have both separately been related to poorer episodic memory and altered hippocampal functioning. Here, we investigated the combined effect of APOE and BDNF on hippocampal activation (N=151). No non-additive interaction effects were seen. Instead, the results revealed decreased activation in bilateral hippocampus and parahippocampus as a function of the number of APOE ε4 and BDNF Met alleles present (neither, one, or both). The combined effect was stronger than either of the individual effects, and both gene variables explained significant proportions of variance in BOLD signal change. Thus, there was an additive gene-gene effect of APOE and BDNF on medial temporal lobe (MTL) activation, showing that a larger proportion of variance in brain activation attributed to genetics can be explained by considering more than one gene variant. This effect might be relevant for the understanding of normal variability in memory function as well as memory-related disorders associated with APOE and BDNF.

BACKGROUND Urine albumin is the primary biomarker for detection and monitoring of kidney damage. Because fixed decision criteria are used to identify patients with increased values, we investigated if commonly used routine measurement procedures gave comparable results. METHODS Results from 17 commercially available urine albumin measurement procedures were investigated vs an isotope dilution mass spectrometry (IDMS) procedure. Nonfrozen aliquots of freshly collected urine from 332 patients with chronic kidney disease, diabetes, cardiovascular disease, and hypertension were distributed to manufacturers to perform urine albumin measurements according to the respective instructions for use for each procedure. Frozen aliquots were used for measurements by the IDMS procedure. An error model was used to determine imprecision and bias components. RESULTS Median differences between the largest positive and negative biases vs IDMS were 45%, 37%, and 42% in the concentration intervals of 12–30 mg/L, 31–200 mg/L, and 201–1064 mg/L, respectively. Biases varied with concentration for most procedures and exceeded ±10% over the concentration interval for 14 of 16 quantitative procedures. Mean biases ranged from −35% to 34% at 15 mg/L. Dilution of samples with high concentrations introduced bias for 4 procedures. The combined CV was >10% for 5 procedures. It was not possible to estimate total error due to dependence of bias on concentration. CVs for sample-specific influences were 0% to 15.2%. CONCLUSIONS Bias was the dominant source of disagreement among routine measurement procedures. Consequently, standardization efforts will improve agreement among results. Variation of bias with concentration needs to be addressed by manufacturers.

Objectives. The aim of this study was to investigate whether leisure activity is associated with incident dementia in an older sample.

leukocyte telomere length (TL) is considered a marker of biological aging. Several studies have investigated the link between leukocyte TL and aging-associated functional attributes of the brain, but no prior study has investigated whether TL can be linked to brain atrophy and white matter hyperintensities (WMHs); two prominent structural manifestations of brain aging.we investigated whether leukocyte TL was related to brain atrophy and WMHs in a sample of 102 non-demented individuals aged 64-75 years.shorter TL was related to greater degree of subcortical atrophy (β = -0.217, P = 0.034), but not to cortical atrophy. Furthermore, TL was 371 bp shorter (P = 0.041) in participants exhibiting subcortical WMHs, and 552 bp shorter (P = 0.009) in older participants exhibiting periventricular WMHs.this study provides the first evidence of leukocyte TL being associated with cerebral subcortical atrophy and WMHs, lending further support to the concept of TL as a marker of biological aging, and in particular that of the aging brain.

Background:The impact of stressful life events as a risk factor of dementia diseases is inconclusive. We sought to determine whether stressful negative life events are associated with incidental dementia in a population-based study with long-term follow-up. We also tested the hypothesis that the occurrence of positive life events could mitigate or overcome the possible adverse effects of negative life events on dementia conversion.Methods:The study involved 2,462 dementia-free participants aged 55 years and older. Information on life events was ascertained at baseline from a comprehensive Life Event Inventory, which included 56 questions about specific life events. For each life event, the emotional impact (both positive and negative) and emotional adjustment were asked for.Results:During follow-up, 423 participants developed dementia; of these, 240 developed Alzheimer's disease (AD). Cox regression analysis showed no association between the total number of negative life events and the incidence of dementia when adjusted solely for age and gender (hazard ratio = 0.97, 95% CI = 0.92–1.02), or with multiple adjustments for a range of covariates (hazard ratio = 0.96, 95% CI = 0.91–1.01). Similarly, neither emotional impact nor emotional adjustment to these life events was associated with incident dementia. A separate analysis of AD did not alter the results.Conclusions:The result of this population-based study finds no association between negative or positive life events and dementia. Accordingly, our results reject the hypothesis that stressful life events trigger the onset of dementia diseases.

Several judgment and decision-making tasks are assumed to involve memory functions, but significant knowledge gaps on the memory processes underlying these tasks remain. In a study on 568 adults between 25 and 80 years of age, hypotheses were tested on the specific relationships between individual differences in working memory, episodic memory, and semantic memory, respectively, and 6 main components of decision-making competence. In line with the hypotheses, working memory was positively related with the more cognitively demanding tasks (Resistance to Framing, Applying Decision Rules, and Under/Overconfidence), whereas episodic memory was positively associated with a more experience-based judgment task (Recognizing Social Norms). Furthermore, semantic memory was positively related with 2 more knowledge-based decision-making tasks (Consistency in Risk Perception and Resistance to Sunk Costs). Finally, the age-related decline observed in some of the decision-making tasks was (partially or totally) mediated by the age-related decline in working memory or episodic memory. These findings are discussed in relation to the functional roles fulfilled by different memory processes in judgment and decision-making tasks.

The study adopted CFA to investigate the factorial structure and reduce the number of items of the Cognitive Dysfunction Questionnaire (CDQ; Vestergren, Ronnlund, Nyberg, & Nilsson, 2011). The ...

Motor-function encoding action phrases, facilitates recollection more than verbal encoding (enactment effect, c.f. Nilsson, 2000). Further, if the phrases are intended to be recalled via motor-function encoding it also leads to higher memory accessibility, referred to as the intention-superiority effect (Goschke & Kuhl, 1993) or the intended enactment effect (Freeman & Ellis, 2003), depending on whether the same process or different processes are assumed to underlie both effects. In three experiments, both effects were studied as a function of list length (18, 30, 60, or 90 items), retrieval measures (free recall, cued recall and recognition). Additionally, different moderator variables for these effects were investigated (familiarity, degree of motor involvement of the action phrases, individual differences in action orientation). Similar effects of intended and actual enactment were found for memory accuracy and accessibility (i.e., response latencies), but the effects were moderated by the nature of the action phrase and action orientation. State-oriented individuals and highly motoric action phrases showed a pronounced (intended) enactment effect. The results, at least partially, support a common explanation for both effects.

By integrating behavioral measures and imaging data, previous investigations have explored the relationship between biological markers of aging and cognitive functions. Evidence from functional and structural neuroimaging has revealed that hippocampal volume and activation patterns in the medial temporal lobe (MTL) may predict cognitive performance in old age. Most past demonstrations of age-related differences in brain structure-function were based on cross-sectional comparisons. Here, the relationship between 6-year intraindividual change in functional magnetic resonance imaging (fMRI) signal and change in memory performance over 2 decades was examined. Correlations between intraindividual change in fMRI signal during episodic encoding and change in memory performance measured outside of scanning were used as an estimate for relating brain-behavior changes. The results revealed a positive relationship between activation change in the hippocampus (HC) and change in memory performance, reflecting reduced hippocampal activation in participants with declining performance. Using a similar analytic approach as for the functional data, we found that individuals with declining performance had reduced HC volume compared with individuals with intact performance. These observations provide a strong link between cognitive change in older adults and MTL structure and function and thus provide insights into brain correlates of individual variability in aging trajectories.

Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated the effect of KIBRA on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal activation in noncarriers of the T allele during retrieval. Noncarriers were interpreted to need more hippocampal activation to reach the same performance level as T carriers. Using large behavioral (N= 2230) and fMRI (N= 83) samples, we replicated the KIBRA effect on episodic memory performance, but found increased hippocampal activation in T carriers during episodic retrieval. There was no evidence of compensatory brain activation in noncarriers within the hippocampal region. In the main fMRI sample, T carriers performed better than noncarriers during scanning but, importantly, the difference in hippocampus activation remained afterpost hocmatching according to performance, sex, and age (N= 64). These findings link enhanced memory performance in KIBRA T allele carriers to elevated hippocampal functioning, rather than to neural compensation in noncarriers.

The catechol O-methyltransferase (COMT) gene—encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)—contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic–phasic hypothesis, individuals carrying the low-enzyme-activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic–phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic–phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val158met polymorphism on different components of working memory.

The use of immobilization matrix in bio-processing is a promising approach to immobilize a catalytic strain for production of biomolecules. In this study, a novel immobilization system of agarose-alginate cryogel was developed in the format of beads and characterized to facilitate the effective cell immobilization followed by enhanced solvent production compared to other immobilization matrix. Cryogel beads showed macroporous internal architecture and nano-range grooves on outer periphery. Study suggests that these grooves facilitate the convective medium transport throughout the cryogel beads in order to eliminate the substrate and product inhibition and also prevent cell leakage. The immobilization study was carried out on a typical anaerobic system of Clostridium acetobutylicum ATCC 824 for butanol production. The experiment was carried out in three different sets (A, B and C) with varying medium and substrate concentration. The adsorption of cells on agarose-alginate cryogel beads produced 11.79 g/l of butanol and 21.64 g/l total ABE (acetone, butanol and ethanol), while entrapment of cells on agarose-alginate cryogel beads showed high glucose consumption, high butanol and total ABE production that was 92.16%, 14.47 g/l and 27.80 g/l, respectively, which was much higher than the control and other matrices.

Background: Methods from 7 manufacturers and 1 distributor for directly measuring HDL cholesterol (C) and LDL-C were evaluated for imprecision, trueness, total error, and specificity in nonfrozen serum samples.Methods: We performed each direct method according to the manufacturer’s instructions, using a Roche/Hitachi 917 analyzer, and compared the results with those obtained with reference measurement procedures for HDL-C and LDL-C. Imprecision was estimated for 35 runs performed with frozen pooled serum specimens and triplicate measurements on each individual sample. Sera from 37 individuals without disease and 138 with disease (primarily dyslipidemic and cardiovascular) were measured by each method. Trueness and total error were evaluated from the difference between the direct methods and reference measurement procedures. Specificity was evaluated from the dispersion in differences observed.Results: Imprecision data based on 4 frozen serum pools showed total CVs Conclusions: Six of 8 HDL-C and 5 of 8 LDL-C direct methods met the National Cholesterol Education Program total error goals for nondiseased individuals. All the methods failed to meet these goals for diseased individuals, however, because of lack of specificity toward abnormal lipoproteins.

Background: The common cause account suggests that there is a third factor causing aging effects in both sensory and cognitive functioning, hypothesized to be the integrity of the central nervous system [Lindenberger and Baltes; Psychol Aging 1994;9:339–355]. Importantly, the common cause account was developed based on cross-sectional data, which are especially biased by cohort effects. However, cohort effects can be controlled for in narrow age cohort (NAC) designs and by longitudinal examination. Findings from the few longitudinal studies that have studied the relation between age-related changes in sensory and cognitive functions are complex and give only partial support to the common cause account. Objective: The present paper examines the common cause account within a longitudinal setting. Method: Our study is unique in the sense that it tests the common cause account within a longitudinal NAC design using data from the Betula project. The participants (n = 1,057) were in the age range of 45–90 years. Results: The findings indicate that the relationship between sensory and memory functioning in both a longitudinal age-heterogeneous and a longitudinal NAC design are much weaker than that detected by an age-heterogeneous cross-sectional design. Conclusion: The demonstrated weak age-associated sensory-cognitive link raises questions regarding the explanatory value of the common cause account and related theoretical accounts for accounting for age-related cognitive changes.

Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10−08). Suggestive associations (Meta P value

Background Exposure to ambient air pollution is suspected to cause cognitive effects, but a prospective cohort is needed to study exposure to air pollution at the home address and the incidence of dementia. Objectives We aimed to assess the association between long-term exposure to traffic-related air pollution and dementia incidence in a major city in northern Sweden. Methods Data on dementia incidence over a 15-year period were obtained from the longitudinal Betula study. Traffic air pollution exposure was assessed using a land-use regression model with a spatial resolution of 50 m × 50 m. Annual mean nitrogen oxide levels at the residential address of the participants at baseline (the start of follow-up) were used as markers for long-term exposure to air pollution. Results Out of 1,806 participants at baseline, 191 were diagnosed with Alzheimer’s disease during follow-up, and 111 were diagnosed with vascular dementia. Participants in the group with the highest exposure were more likely than those in the group with the lowest exposure to be diagnosed with dementia (Alzheimer’s disease or vascular dementia), with a hazard ratio (HR) of 1.43 (95% CI: 0.998, 2.05 for the highest vs. the lowest quartile). The estimates were similar for Alzheimer’s disease (HR 1.38) and vascular dementia (HR 1.47). The HR for dementia associated with the third quartile versus the lowest quartile was 1.48 (95% CI: 1.03, 2.11). A subanalysis that excluded a younger sample that had been retested after only 5 years of follow-up suggested stronger associations with exposure than were present in the full cohort (HR = 1.71; 95% CI: 1.08, 2.73 for the highest vs. the lowest quartile). Conclusions If the associations we observed are causal, then air pollution from traffic might be an important risk factor for vascular dementia and Alzheimer’s disease. Citation Oudin A, Forsberg B, Nordin Adolfsson A, Lind N, Modig L, Nordin M, Nordin S, Adolfsson R, Nilsson LG. 2016. Traffic-related air pollution and dementia incidence in northern Sweden: a longitudinal study. Environ Health Perspect 124:306–312; http://dx.doi.org/10.1289/ehp.1408322

Background: Bipolar disorders are often not recognized. Several instruments were developed but none primarily focused on hypomania. The Hypomania Checklist (HCL) is aimed at the identification of bipolarity in outpatients. Using a German and Swedish sample, we investigated if the factor structure in nonclinical samples is similar to the one reported for outpatient samples. Furthermore, we tested if people who probably had a lifetime history of hypomania report more depression or other signs of impairment and if current depression is associated with lifetime hypomania. Method: In the German study, participants completed the HCL-32 as an online questionnaire that also included questions about lifetime and current depression (n = 695), whereas the Swedish data relied on the paper-and-pencil version of the HCL-32 completed by a random sample from a representative population sample (n = 408). Results: The factor structure of the HCL-32 was fairly similar in both samples and to the ones presented by Angst et al (J Affect Disord 2005;88:217-33). People reporting “highs” (≥4 days and experiencing negative consequences) not only endorsed more HCL-32 symptoms but also had higher rates of current and former depression and psychotherapy. Level of current depression was also associated with lifetime hypomanic symptoms. Discussion and limitation: An “active-elated” and “risk-taking/irritable” factor of hypomania can be distinguished with the HCL-32 in clinical and nonclinical samples. Based on our results, the HCL-32 might even be useful as screening tool in nonclinical samples and not only in depressed outpatients. However, our data do not allow estimating sensitivity and specificity of the HCL-32 because structured clinical interviews were not included.

Background/Aims: Early dementia diagnosis is a considerable challenge. The present study examined the predictive value of cognitive performance for a future clinical diagnosis of late-onset Alzheimer's disease or vascular dementia in a random population sample. Methods: Cognitive performance was retrospectively compared between three groups of participants from the Betula longitudinal cohort. Group 1 developed dementia 11-22 years after baseline testing (n = 111) and group 2 after 1-10 years (n = 280); group 3 showed no deterioration towards dementia during the study period (n = 2,855). Multinomial logistic regression analysis was used to investigate the predictive value of tests reflecting episodic memory performance, semantic memory performance, visuospatial ability, and prospective memory performance. Results: Age- and education-corrected performance on two free recall episodic memory tests significantly predicted dementia 10 years prior to clinical diagnosis. Free recall performance also predicted dementia 11-22 years prior to diagnosis when controlling for education, but not when age was added to the model. Conclusion: The present results support the suggestion that two free recall-based tests of episodic memory function may be useful for detecting individuals at risk of developing dementia 10 years prior to clinical diagnosis.

Background: Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. Methods: We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 +/- 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. Results: A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity. Conclusions: This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

This study examined age differences in the use of an electronic three-dimensional (3D) environment, and how the age differences were affected by the use of an overview map as a navigation aid. Task performance and the subjects' acquisition of configural knowledge of the 3D-environment were assessed. Impact of spatial ability and prior experience on these measurements were also investigated. One group of older subjects (n = 24) and one group of younger subjects (n = 24) participated. An overall hypothesis for the work presented here was that differences in learning to and performing navigational tasks in the physical world are similar in learning and performing navigational tasks in the virtual world. The results showed that the older participants needed more time to solve the tasks; and similar to navigation in the physical world, the older participants were less likely to create configural knowledge. It could not be established that older participants benefited more from an overview map as cognitive support than younger subjects, except in the subjective sense: the older users felt more secure when the map was there. The map seemed to have supported the older users in creating a feeling of where objects were located within the environment, but it did not make them more efficient. The results have implications for design; in particular, it brings up the difficult issue of balancing design goals such as efficiency in terms of time and functionality, against maintaining a sense of direction and location in navigational situations.

To explore neural correlates of cognitive decline in aging, we used longitudinal behavioral data to identify two groups of older adults (n = 40) that differed with regard to whether their performance on tests of episodic memory remained stable or declined over a decade. Analysis of structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline. Manual tracing of hippocampal volume showed significant reduction in those older adults with a declining memory performance as did DTI-measured fractional anisotropy in the anterior corpus callosum. Functional magnetic resonance imaging during incidental episodic encoding revealed increased activation in left prefrontal cortex for both groups and additional right prefrontal activation for the elderly subjects with the greatest decline in memory performance. Moreover, mean DTI measures in the anterior corpus callosum correlated negatively with activation in right prefrontal cortex. These results demonstrate that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggest that increased activation is either caused by structural disruption or is a compensatory response to such disruption.

This paper presents the cognitive test battery used in the Cascade Study (Cardiovascular Determinants of Dementia) for examining the consequences of cerebral white matter lesions and atrophy. The test battery includes nine different tasks assessing memory, executive function, and global cognitive function. Three episodic memory tasks were used in combinations to assess the role of attention and speed on encoding. Estimates of short- and long-term memory capacity were also derived from these three memory tasks. Semantic memory production / frontal lobe functions were assessed by means of a word fluency test. The Letter Digit Substitution test and the Stroop test were used to assess speed of processing and attention. Motor speed was measured with the Purdue Pegboard test, and global cognitive function was assessed by the Mini Mental State Examination. Overall performance data for the whole Cascade sample and for each of eight study centers are presented for each test. Possible reasons for performan...

Diabetic patients are at increased risk for stroke, but little is known about the presence of other brain lesions. We studied the association of magnetic resonance imaging–detected brain lesions to diabetes in 1,252 individuals aged 65–75 years who were randomly selected from eight European population registries or defined working populations. All scans were centrally read for brain abnormalities, including infarcts, white matter lesions, and atrophy. We used a three-point scale to rate periventricular white matter lesions, and the volume of subcortical lesions was calculated according to their number and size. Subjective grading of cortical atrophy by lobe and summation of the lobar grades resulted in a total cortical atrophy score. The mean of three linear measurements of the ventricular diameter relative to the intracranial cavity defined the severity of subcortical atrophy. After adjustment for possible confounders, diabetes was associated with cortical brain atrophy but not with any focal brain lesions or subcortical atrophy. There was a strong interaction of diabetes and hypertension, such that the association between diabetes and cortical atrophy existed only in hypertensive but not in normotensive participants. Cognitive and pathological data are needed to determine the clinical significance of these findings as well as to understand the mechanisms underlying these associations.

We examined recollective experience as a function of sex for olfactory and verbal information. In the first study, men and women studied a set of highly familiar odors with incidental or intentional encoding instructions. In the second study, participants were presented with a number of sentences. At recognition, participants indicated whether their positive response was based on conscious recollection (remembering), a feeling of familiarity (knowing), or guessing. The results indicated that recollection was higher among women than men, and that familiarity-based recognition was equally large across sex for both types of information.The finding that the sex-related experiential difference disappeared when controlling for verbal proficiency suggests that sex-related differences in activating verbal information play an important role for sex differences in recollective experience.

Robust statistical, genetic and functional evidence supports a role for DISC1 in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders. In this study, CNV analysis of DISC1 and its binding partners PAFAH1B1, NDE1, NDEL1, FEZ1, MAP1A, CIT and PDE4B in Scottish and Northern Swedish population-based samples was carried out using multiplex amplicon quantification. Here, we report the finding of rare CNVs in DISC1, NDE1 (together with adjacent genes within the 16p13.11 duplication), NDEL1 (including the overlapping MYH10 gene) and CIT. Our findings provide further evidence for involvement of DISC1 and its interaction partners in neuropsychiatric disorders and also for a role of structural variants in the aetiology of these devastating diseases.