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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.

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.

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.

To determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period.Prospective cohort study.Betula Study, Umeå, Sweden.A population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).Olfactory performance using the Scandinavian Odor-Identification Test (SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade.Within the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71-0.77, P.001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables (HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction.Poor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.

Supplemental Material, JBD851576_supplemental_material for On the use of growth models to study normal cognitive aging by Paolo Ghisletta, Fabio Mason, Timo von Oertzen, Christopher Hertzog, Lars-Göran Nilsson and Ulman Lindenberger in International Journal of Behavioral Development

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.

The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memory and olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45-90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10-20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by >1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator.

Identification of novel candidate genes for schizophrenia (SZ) and bipolar disorder (BP), two psychiatric disorders with large epidemiological impacts, is a key research area in neurosciences and psychiatric genetics. Previous evidence from genome-wide studies suggests an important role for genes involved in synaptic plasticity in the risk for SZ and BP. We used a convergent genomics approach, combining different lines of biological evidence, to identify genes involved in the cAMP/PKA/CREB functional pathway that could be novel candidates for BP and SZ: CREB1, CREM, GRIN2C, NPY2R, NF1, PPP3CB and PRKAR1A. These 7 genes were analyzed in a HapMap based association study comprising 48 common SNPs in 486 SZ, 351 BP patients and 514 control individuals recruited from an isolated population in Northern Sweden. Genetic analysis showed significant allelic associations of SNPs in PRKAR1A with SZ and of PPP3CB and PRKAR1A with BP. Our results highlight the feasibility and the importance of convergent genomic data analysis for the identification of candidate genes and our data provide support for the role of common inherited variants in synaptic genes and their involvement in the etiology of BP and SZ. (C) 2016 Elsevier B.V. All rights reserved.

Recent findings indicate that bilingualism delay the onset of dementia. Using data from the Betula longitudinal cohort study on memory, health and aging (www.betula.su.se) the issue of a possible protective effect of bilingualism was addressed. Monolingual (n = 736) and bilingual (n = 82) participants (≥ 60 years) without dementia at inclusion were followed for incident dementia over a time-period up to 10 years. In total, 112 participants developed dementia. Analyses were performed with Cox proportional hazards regression adjusted for age, sex, and presence/absence of the Apolipoprotein E (APOE) ɛ4 allele, with dementia outcome as the dependent variable. Results showed no delayed onset of dementia in bilinguals compared to monolinguals. However, because of the findings from a study using participants from the same population showing beneficial longitudinal effects of bilingualism on episodic memory; we argue that our results may depend on the frequency of use of the second language after retirement.

Background Automated peritoneal dialysis (APD) is a growing PD modality but as with other home dialysis methods, the lack of monitoring of patients’ adherence to prescriptions is a limitation with potential negative impact on clinical outcome parameters. Remote patient monitoring (RPM) allowing the clinical team to have access to dialysis data and adjust the treatment may overcome this limitation. The present study sought to determine clinical outcomes associated with RPM use in incident patients on APD therapy. Methods A retrospective cohort study included 360 patients with a mean age of 57 years (diabetes 42.5%) initiating APD between 1 October 2016 and 30 June 2017 in 28 Baxter Renal Care Services (BRCS) units in Colombia. An RPM program was used in 65 (18%) of the patients (APD-RPM cohort), and 295 (82%) were treated with APD without RPM. Hospitalizations and hospital days were recorded over 1 year. Propensity score matching 1:1, yielding 63 individuals in each group, was used to evaluate the association of RPM exposure with numbers of hospitalizations and hospital days. Results After propensity score matching, APD therapy with RPM ( n = 63) compared with APD-without RPM ( n = 63) was associated with significant reductions in hospitalization rate (0.36 fewer hospitalizations per patient-year; incidence rate ratio [IRR] of 0.61 [95% confidence interval (CI) 0.39 – 0.95]; p = 0.029) and hospitalization days (6.57 fewer days per patient-year; IRR 0.46 [95% CI 0.23 – 0.92]; p = 0.028). Conclusions The use of RPM in APD patients is associated with lower hospitalization rates and fewer hospitalization days; RPM could constitute a tool for improvement of APD therapy.

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 ...

Testing memory typically enhances subsequent re-encoding of information (“indirect” testing effect) and, as compared to restudy, it also benefits later long-term retention (“direct” testing effect). We investigated the effect of testing on subsequent restudy and 1-week retention of action events (e.g. “water the plant”). In addition, we investigated if the type of recall practice (noun-cued vs. verb-cued) moderates these testing benefits. The results showed an indirect testing effect that increased following noun-cued recall of verbs as compared to verb-cued recall of nouns. In contrast, a direct testing effect on the forgetting rate of performed actions was not reliably observed, neither for noun- nor verb-cued recall. Thus, to the extent that this study successfully dissociated direct and indirect testing-based enhancements, they seem to be differentially effective for performed actions, and may rely on partially different mechanisms.

The objective of the study was to examine the degree of stability of interindividual differences in general cognitive ability (g) across the adult life span. To this end, we examined a sample of me ...

OBJECTIVES: To examine the association between self-reported memory failures and incident dementia in individuals aged 60 and older. DESIGN: Longitudinal, community based. SETTING: Betula Prospective Cohort Study, a population-based study in Umea, Sweden. PARTICIPANTS: Individuals with a mean age of 71.5 +/- 8.8 (range 60-90) (N = 1,547). MEASUREMENTS: Participants rated the frequency of everyday memory failures using the 16-item Prospective and Retrospective Memory Questionnaire (PRMQ) and underwent objective memory testing at baseline. Participant self-reports of complaints of poor memory by family and friends were evaluated. Dementia status was followed-up for 10 to 12 years. RESULTS: Over the study period, 225 participants developed dementia (132 with Alzheimer's disease (AD)). In Cox proportional hazard regression models adjusted for demographic factors, PRMQ z-scores predicted incident dementia (hazard ratio (HR) = 1.21 for all-cause dementia; HR = 1.25 for AD, Ps < .01). The significant associations remained when depressive symptoms and objective memory performance were adjusted for, when low performers on objective memory (= 1 standard deviations below the age group mean) were excluded, and in analyses with delayed entry (survival time = 5 years). Similar patterns were observed for the prospective and retrospective subscales, although including how often participants self-reported that others complained about their poor memory eliminated the association between PRMQ scores and dementia and itself emerged as a significant predictor. CONCLUSION: Self-reported memory failure predicted future dementia or AD independent of objective memory performance. Subjective reports of complaints by family and friends appear to be an even more-important indicator of preclinical impairments, and physicians should not ignore them, even in the absence of objective memory deficits.

Cognitive decline has been suggested as an early marker for later onset of Alzheimer’s disease. We therefore explored the relationship between decline in episodic memory and β-amyloid using positron emission tomography (PET) and [11C]AZD2184, a radioligand with potential to detect low levels of amyloid deposits. Healthy elderly subjects with declining (n = 10) or stable (n = 10) episodic memory over 15 years were recruited from the population-based Betula study and examined with PET. Brain radioactivity was measured after intravenous administration of [11C]AZD2184. The binding potential BP ND was calculated using linear graphical analysis with the cerebellum as reference region. The binding of [11C]AZD2184 in total grey matter was generally low in the declining group, whereas some binding could be observed in the stable group. Mean BP ND was significantly higher in the stable group compared to the declining group (p = 0.019). An observation was that the three subjects with the highest BP ND were ApoE e4 allele carriers. We conclude that cognitive decline in the general population does not seem to stand by itself as an early predictor for amyloid deposits.

We investigated the factorial structure of the Perceived Stress Questionnaire (PSQ-recent; Levenstein, Prantera, Varvo et al., 1993) in a large (N = 1516; 35-95 years) population-based Swedish sample (Nilsson, Adolfsson, Bäckman et al., 2004; Nilsson, Bäckman, Erngrund et al., 1997). Exploratory principal components analysis (PCA) was conducted on a first, randomly drawn subsample (n = 506). Next, the model based on the PCA was tested in a second sample (n = 505). Finally, a third sample (n = 505) was used to cross-validate the model. Five components were extracted in the PCA (eigenvalue1) and labeled "Demands," "Worries/Tension," "Lack of joy," "Conflict," and "Fatigue," respectively. Twenty-one out of the 30 original PSQ items were retained in a confirmatory factor analysis (CFA) model that included the five (first-order) factors and, additionally, a general (second-order) stress factor, not considered in prior models. The model showed reasonable goodness of fit [χ(2)(184) = 511.2, p0.001; CFI = 0.904; RMSEA = 0.059; and SRMR = 0.063]. Multigroup confirmatory factor analyses supported the validity of the established model. The results are discussed in relation to prior investigations of the factorial structure of the PSQ.

Introduction The serotonin 5-HT1B receptor subtype is involved in the modulation of serotonin release and is a target of interest for neuroreceptor imaging. Previous studies have shown that the serotonin system is affected in Parkinson's disease (PD). Cognitive function, frequently impaired in PD, has been linked to the serotonin system. The aim of this study was to examine whether 5-HT1B receptor availability in the brain of healthy subjects and PD patients is associated with measures of cognitive function. Methods Twelve control subjects and ten PD patients with normal mini-mental state examination scores were included in this study. Cognitive function was evaluated by assessment of semantic, episodic, and working memory, as well as fluency and visual attention. Creative ability, a measure of divergent thinking, was examined with the alternative uses of objects task. PET measurements were performed with the 5-HT1B receptor-radioligand [11C]AZ10419369 using the HRRT system. Results PD patients showed statistically significant lower measures of semantic and episodic memory, as well as creative ability, compared with control subjects. Statistically significant positive correlations were found in control subjects between creative ability and average 5-HT1B receptor availability in grey matter, and in PD patients between scores of Beck Depression Inventory-II and creative ability. Conclusion Though creativity has been conventionally linked to dopamine function, our findings in control subjects suggest a link between 5-HT1B receptor availability and creative ability. In PD patients, creative ability was significantly associated with depressive symptoms but not with 5-HT1B receptor availability. This finding deserves further investigation in future studies. Synapse 69:365–374, 2015. © 2015 Wiley Periodicals, Inc.

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.

Introduction The objective was to examine whether subjective memory impairment (SMI) predicts all-cause dementia or Alzheimer's disease (AD) in a population-based study with long-term follow-up (median = 10 years). Methods A total of 2043 initially dementia-free participants (≥ 60 years) made three memory ratings ("compared with others", "compared with five years ago", and "complaints from family/friends") at baseline. During follow-up, 372 participants developed dementia (208 with AD). Results Cox regression revealed that subjective memory impairment ratings predicted all-cause dementia in models adjusting for age and sex (hazard ratio or HR from 2.04 to 3.94), with even higher values for AD (HR from 2.29 to 5.74). The result persisted in models including other covariates, including baseline episodic memory performance, and in analyses restricted to participants with long time to dementia diagnosis (≥ 5 years). Discussion The findings underscore the usefulness of subjective memory assessment in combination with other factors in identifying individuals at risk for developing dementia.

Although Lake Vänern is the largest freshwater reservoir in Western Europe, it remains relatively unknown to the scientific community outside of Scandinavia. Therefore, we aim to give a brief outline of the lake and its geological history, in particular the landscape transformation, resource utilization, pollution history, and environmental development of the region. The landscape around Lake Vänern was shaped into its present form during the latest glaciations some 10,000 years ago. Large variation exists in its tributaries, with forest in the north and agricultural areas in the south. Human influence on the landscape was relatively small until the mid-18th century. Later, in the mid-19th century, the agriculture, forestry and shipping industries underwent large transformations as the towns around the lake grew and the economy changed. Development of fishing equipment, processes and changes in catching methods industrialized the fishing industry after mid-20th century. In the 1960s the lake was considered to be one of the most heavily mercury-polluted lakes in the world. After the passing of the first national environmental protection law in Sweden the lake turned into a success story: It has been declared to be healthy. However, old pollution still affects the fishing industry. With this new focus on the environment, the scientific community started to be interested in the lake. The lake has also played a very important role as the largest hydropower reservoir in Sweden. Here, too, the environmental question is in focus and the effects of the water regulation are still under debate. The result has been loss of biodiversity and an increased risk of an inflow of invasive species from international shipping. However, still many questions remain to be answered regarding the lake and effect of ongoing climate change on the sustainable development of the lake region.

Background Previous studies have suggested a link between herpes simplex virus (HSV) type 1 and the development of Alzheimer's disease (AD). Methods The present analysis included 3432 persons (53.9% women, mean age at inclusion 62.7 ± 14.4 years) with a mean follow-up time of 11.3 years. The number of incident AD cases was 245. Serum samples were analyzed for anti-HSV antibodies (immunoglobulin (Ig)G and IgM) by enzyme-linked immunosorbent assays. Results The presence of anti-HSV IgG antibodies was not associated with an increased risk for AD, controlled for age and sex (hazard ratio, HR, 0.993, P = .979). However, the presence of anti-HSV IgM at baseline was associated with an increased risk of developing AD (HR 1.959, P = .012). Conclusion Positivity for anti-HSV IgM, a sign of reactivated infection, was found to almost double the risk for AD, whereas the presence of anti-HSV IgG antibodies did not affect the risk.

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.

Impairment of the central serotonin system in Parkinson's disease (PD) has been shown postmortem and in vivo with positron emission tomography (PET). The aim of this PET study was to examine and compare the availability of the 5-hydroxytryptamine (5-HT)(1B)-receptor subtype in patients with PD and age-matched control subjects. Twelve control subjects and 12 PD patients were examined with PET using the 5-HT(1B)-radioligand [(11)C]AZ10419369. In PD patients, 5-HT(1B)-receptor availability in the right orbitofrontal cortex was lower than in control subjects. A statistically significant negative correlation between 5-HT(1B)-receptor availability and age was obtained for the right temporal cortex in control subjects and for the right midbrain and left parahippocampal gyrus in PD patients. The lower regional 5-HT(1B)-receptor availability is in line with previous studies showing a decrease of serotonin imaging markers in PD and corroborates a role of the serotonin system in the pathophysiology of PD. The demonstrated age effect on 5-HT(1B) receptors suggest a physiologic and PD-related decline of serotonin function, indicating the importance of controlling for age in clinical studies.

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