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Given rapid global population aging, developing interventions against age-associated cognitive decline is an important medical and societal goal. We evaluated a cognitive training protocol combined with transcranial direct current stimulation (tDCS) on trained and non-trained functions in non-demented older adults.Fifty-six older adults (65-80 years) were randomly assigned to one of two interventional groups, using age and baseline performance as strata. Both groups performed a nine-session cognitive training over 3 weeks with either concurrent anodal tDCS (atDCS, 1 mA, 20 minutes) over the left dorsolateral prefrontal cortex (target intervention) or sham stimulation (control intervention). Primary outcome was performance on the trained letter updating task immediately after training. Secondary outcomes included performance on other executive and memory (near and far transfer) tasks. All tasks were administered at baseline, post-intervention, and at 1- and 7-month follow-up assessments. Prespecified analyses to investigate treatment effects were conducted using mixed-model analyses.No between-group differences emerged in the trained letter updating and Markov decision-making tasks at post-intervention and at follow-up timepoints. Secondary analyses revealed group differences in one near-transfer task: Superior n-back task performance was observed in the tDCS group at post-intervention and at follow-up. No such effects were observed for the other transfer tasks. Improvements in working memory were associated with individually induced electric field strengths.Cognitive training with atDCS did not lead to superior improvement in trained task performance compared to cognitive training with sham stimulation. Thus, our results do not support the immediate benefit of tDCS-assisted multi-session cognitive training on the trained function. As the intervention enhanced performance in a near-transfer working memory task, we provide exploratory evidence for effects on non-trained working memory functions in non-demented older adults that persist over a period of 1 month.

Spatial navigation relies on multiple mnemonic mecha- nisms and previous work in younger adults has described two separate types of spatial memory. One type uses directional as well as boundary- related information for spatial memory and mainly implicates the hippo- campal formation. The other type has been linked to directional and landmark-related information and primarily involves the striatum. Using a virtual reality navigation paradigm, we studied the impacts of aging and a single nucleotide polymorphism (SNP rs17070145) of the KIBRA gene (official name: WWC1) on these memory forms. Our data showed that older adult's spatial learning was preferentially related to process- ing of landmark information, whereas processing of boundary informa- tion played a more prominent role in younger adults. Moreover, among older adults T-allele carriers of the examined KIBRA polymorphism showed better spatial learning compared to C homozygotes. Together these findings provide the first evidence for an effect of the KIBRA rs17070145 polymorphism on spatial memory in humans and age differ- ences in the reliance on landmark and boundary-related spatial informa- tion. V C 2013 Wiley Periodicals, Inc.

Aim Hepatic steatosis is an important histopathological feature of chronic hepatitis C virus (HCV) infection. Silent information regulator 1 (SIRT1) plays key role in regulation of hepatic lipid metabolism. We investigated the possible effect of HCV replication on lipid metabolism of hepatocytes and expression of SIRT1 using Huh-7.5 cells harboring HCV replicon. Methods The level of reactive oxygen species (ROS) and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), and the value of nicotinamide adenine dinucleotide (NAD+)/NADH was detected. The level of triacylglycerol (TG), total cholesterol (TC) and fatty acid β-oxidation rate was detected. The activity and expression levels of SIRT1 and expression of its downstream lipid-metabolism genes were measured. Results In replicon cells, the level of ROS and MDA increased, SOD activity and the value of NAD+/NADH decreased, then the activity and expression level of mRNA and protein of SIRT1 reduced. Inhibition of SIRT1 decreased phosphorylation of forkhead box O1 (FoxO1), which not only upregulated SREBP-1c, FAS, ACC, SREBP-2, HMGR and HMGS genes and increased fatty acid synthesis; but also downregulated PPAR-α and CPT1A genes and decreased fatty acid β-oxidation. Interferon treatment restored aforementioned changes. SIRT1 activator improved lipid metabolism disorders by an increase in fatty acid β-oxidation and a decrease in TG and TC synthesis and inhibited HCV replication. Conclusion HCV replication decreasing NAD+/NADH ratio may downregulate the activity and the expression of SIRT1, then change the expression profile of lipid metabolism-related genes, thereby cause lipid metabolism disorders of hepatocytes and promote HCV replication. Treatment with SIRT1 activator ameliorates lipid metabolic disorders and inhibits HCV replication.

The reliability, stability, and signal-to-noise ratio (SNR) of event-related potentials (ERPs) were investigated in children, adolescents, younger adults, and older adults in performance monitoring tasks. P2, N2, P3, and P2-N2 peak-to-peak amplitude showed high odd-even split reliabilities in all age groups, ranging from .70 to .90. Multigroup analyses showed that test-retest stabilities (across 2 weeks) of ERP amplitudes did not differ among the four age groups. In contrast, relative to adolescents and younger adults, SNRs were lower in children and older adults, with higher noise levels in children and lower signal power in older adults. We conclude that age differences in the SNR of stimulus-locked ERPs can be successfully compensated by the averaging procedure with about 40 trials in the average. However, age differences in baseline noise and split-half reliability should be considered when comparing age groups in single trial measures or time-varying processes with ERPs.

In this paper, we review the current literature to highlight relations between age-associated declines in dopaminergic and serotonergic neuromodulation and adult age differences in adaptive goal-directed behavior. Specifically, we focus on evidence suggesting that deficits in neuromodulation contribute to older adults’ behavioral disadvantages in learning and decision making. These deficits are particularly pronounced when reward information is uncertain or the task context requires flexible adaptations to changing stimulus–reward contingencies. Moreover, emerging evidence points to age-related differences in the sensitivity to rewarding and aversive outcomes during learning and decision making if the acquisition of behavior critically depends on outcome processing. These age-related asymmetries in outcome valuation may be explained by age differences in the interplay of dopaminergic and serotonergic neuromodulation. This hypothesis is based on recent neurocomputational and psychopharmacological approaches, which suggest that dopamine and serotonin serve opponent roles in regulating the balance between approach behavior and inhibitory control. Studying adaptive regulation of behavior across the adult life span may shed new light on how the aging brain changes functionally in response to its diminishing resources.

Background and Aims: Chronic hepatitis B virus (HBV) infection is a major global health issue, and the prognosis of patients with HBV-associated acute-on-chronic hepatic failure (ACLF) is extremely poor. In this study, the efficacy of lamivudine was investigated in patients with ACLF. The effects of HBV DNA load and its related factors on the prognosis were also further explored. Methods: A matched retrospective cohort study using data on ACLF patients derived from our hospital database was conducted. One hundred and thirty patients receiving lamivudine were selected into the lamivudine treatment group with another 130 without lamivudine treatment studied as control. They were matched for sex, age and imaging finding with the lamivudine treatment group. All the patients were followed up for 3 months and the survival rates were compared. The influential factors on the mortality were studied by the Cox proportional hazards model. Results: The cumulative survival rates of patients in the lamivudine group were higher than those of the control group (χ2 = 9.50, P = 0.0021). The mortality of patients in the high virus load group (71/95, 74.7%) was higher than that of those in the low virus load group (15/29, 51.7%) (χ2 = 5.536, P = 0.019). For patients with a Model for End-Stage Liver Disease (MELD) score of 20–30 by week 4, the mortality of those with HBV DNA that was undetectable or declined for more than 2 log10 (2/12, 16.7%; 18/40, 45.0%) was lower than that of those with a less than 2 log10 decline (18/23, 78.3%) (χ2 = 10.106, P = 0.001). In the Cox proportional hazards model, for patients with a MELD score of 20–30, treatment method (P = 0.002), pretreatment HBV DNA load (P = 0.007) and decline of HBV DNA load during therapy (P = 0.003) were independent predictors; for those with a MELD score of above 30, MELD score (P = 0.008) was the only independent predictor. Conclusion: Lamivudine can significantly decrease the 3-month mortality of patients with a MELD score of 20–30, and a low pretreatment viral load and rapid decline of HBV DNA load are good predictors for the outcome of the treatment.

Phenomena of aging effects on intellectual and cognitive functioning are investigated by research approaches at the psychometric, information-processing, and biological levels. Evidence from these approaches complements each other and should be considered conjointly for a comprehensive overview of aging and intelligence. Recent neurcomputational approaches help to integrate theory and data across these levels. Keywords: intelligence; psychometric; neurocomputational; processing speed; executive control

OBJECTIVE To study the virological features of patients coinfected with hepatitis B virus (HBV) and hepatitis C virus (HCV) and the efficacy of combination therapy with peginterferon alpha-2a and ribavirin in these patients. METHODS The epidemiological and virological data of 50 patients coinfected with HBV and HCV were analysed. The virological response rates of patients treated with peginterferon alpha-2a and ribavirin between the HBV and HCV coinfection group and the HCV monoinfection group were compared. RESULTS HCV-dominant virus strains accounted for 92.0% of the 50 coinfected individuals, and HCV- and HBV-dominant virus strains accounted for the remaining 8.0%. The HBV DNA level of the patients coinfected with HBV and HCV was 4.6+/-0.9 log(10) copies/ml, which was significantly lower than that in the HBV monoinfection group (5.9+/-1.2 log(10) copies/ml) (t=5.964, P

Founded in 1981 by the late Paul B. Baltes, the Center for Lifespan Psychology at the Max Planck Institute for Human Development has helped to establish lifespan psychology as a distinct conceptual approach within developmental psychology. Recently, the Center has extended its research programme into developmental behavioural neuroscience. Here, we provide an overview of the Center's conceptual agenda, and present two of its seven research projects in greater detail. Work at the Center is guided by three propositions: (1) to study lifespan changes in behaviour as interactions among maturation, learning, and senescence; (2) to develop theories and methods that integrate empirical evidence across domains of functioning, timescales, as well as behavioural and neuronal levels of analysis; (3) to identify mechanisms of development by exploring age‐graded differences in plasticity. The Intra‐Person Dynamics Project studies the organization of cognitive abilities within individuals of different ages, and investi...

Executive functions that are dependent upon the frontal‐parietal network decline considerably during the course of normal aging. To delineate neuroanatomical correlates of age‐related executive impairment, we investigated the relation between cortical thickness and executive functioning in 73 younger (20–32 years) and 56 older (60–71 years) healthy adults. Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). Cortical thickness was measured at each location of the cortical mantle using surface‐based segmentation procedures on high‐resolution T1‐weighted magnetic resonance images. For regions involved in WCST performance, such as the lateral prefrontal and parietal cortices, we found that thicker cortex was related to higher accuracy. Follow‐up ROI‐based analyses revealed that these associations were stronger in older than in younger adults. Moreover, among older adults, high and low performers differed in cortical thickness within regions generally linked to WCST performance. Our results indicate that the structural cortical correlates of executive functioning largely overlap with previously identified functional patterns. We conclude that structural preservation of relevant brain regions is associated with higher levels of executive performance in old age, and underscore the need to consider the heterogeneity of brain aging in relation to cognitive functioning. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.