Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model

Latrepirdine (Dimebon) is a pro-neurogenic, antihistaminic compound that has yielded mixed results in clinical trials of mild to moderate Alzheimer's disease, with a dramatically positive outcome in a Russian clinical trial that was unconfirmed in a replication trial in the United States. We sought to determine whether latrepirdine (LAT)-stimulated amyloid precursor protein (APP) catabolism is at least partially attributable to regulation of macroautophagy, a highly conserved protein catabolism pathway that is known to be impaired in brains of patients with Alzheimer's disease (AD). We utilized several mammalian cellular models to determine whether LAT regulates mammalian target of rapamycin (mTOR) and Atg5-dependent autophagy. Male TgCRND8 mice were chronically administered LAT prior to behavior analysis in the cued and contextual fear conditioning paradigm, as well as immunohistological and biochemical analysis of AD-related neuropathology. Treatment of cultured mammalian cells with LAT led to enhanced mTOR- and Atg5-dependent autophagy. Latrepirdine treatment of TgCRND8 transgenic mice was associated with improved learning behavior and with a reduction in accumulation of Aβ42 and α-synuclein. We conclude that LAT possesses pro-autophagic properties in addition to the previously reported pro-neurogenic properties, both of which are potentially relevant to the treatment and/or prevention of neurodegenerative diseases. We suggest that elucidation of the molecular mechanism(s) underlying LAT effects on neurogenesis, autophagy and behavior might warranty the further study of LAT as a potentially viable lead compound that might yield more consistent clinical benefit following the optimization of its pro-neurogenic, pro-autophagic and/or pro-cognitive activities.

Executive functioning, metacognition, and self-perceived competence in elementary school children: An explorative study on their interrelations and their role for school achievement

In the present study, associations between executive functioning, metacognition, and self-perceived competence in the context of early academic outcomes were examined. A total of 209 children attending first grade were initially assessed in terms of their executive functioning and academic self-concept. One year later, children’s executive functioning, academic self-concept, metacognitive monitoring and control, as well as their achievement in mathematics and literacy were evaluated. Structural equation modeling revealed that executive functioning was significantly related to metacognitive control, both cross-sectionally and longitudinally, and that self-concept was substantially associated with metacognitive monitoring, both cross-sectionally and longitudinally. Individual differences in executive functioning and metacognitive control were significantly related to academic outcomes, with metacognitive control appearing to yield a more circumscribed influence on academic outcomes (only literacy) compared to executive functioning (literacy and mathematics).

Spatial cognition, body representation and affective processes: the role of vestibular information beyond ocular reflexes and control of posture

A growing number of studies in humans demonstrate the involvement of vestibular information in tasks that are seemingly remote from well-known functions such as space constancy or postural control. In this review article we point out three emerging streams of research highlighting the importance of vestibular input: (1) Spatial Cognition: Modulation of vestibular signals can induce specific changes in spatial cognitive tasks like mental imagery and the processing of numbers. This has been shown in studies manipulating body orientation (changing the input from the otoliths), body rotation (changing the input from the semicircular canals), in clinical findings with vestibular patients, and in studies carried out in microgravity. There is also an effect in the reverse direction; top-down processes can affect perception of vestibular stimuli. (2) Body Representation: Numerous studies demonstrate that vestibular stimulation changes the representation of body parts, and sensitivity to tactile input or pain. Thus, the vestibular system plays an integral role in multisensory coordination of body representation. (3) Affective Processes and Disorders: Studies in psychiatric patients and patients with a vestibular disorder report a high comorbidity of vestibular dysfunctions and psychiatric symptoms. Recent studies investigated the beneficial effect of vestibular stimulation on psychiatric disorders, and how vestibular input can change mood and affect. These three emerging streams of research in vestibular science are—at least in part—associated with different neuronal core mechanisms. Spatial transformations draw on parietal areas, body representation is associated with somatosensory areas, and affective processes involve insular and cingulate cortices, all of which receive vestibular input. Even though a wide range of different vestibular cortical projection areas has been ascertained, their functionality still is scarcely understood.

Head movement synchrony in social interactions of patients with schizophrenia indicates symptoms, cognition and social functioning

Background: Disturbed interpersonal communication is a core problem in schizophrenia. Patients with schizophrenia often appear disconnected and "out of sync" when interacting with others. This may involve perception, cognition, motor behavior, and nonverbal expressiveness. Although well-known from clinical observation, mainstream research has neglected this area. Corresponding theoretical concepts, statistical methods, and assessment were missing. In recent research, however, it has been shown that objective, video-based measures of nonverbal behavior can be used to reliably quantify nonverbal behavior in schizophrenia. Newly developed algorithms allow for a calculation of movement synchrony. We found that the objective amount of movement of patients with schizophrenia during social interactions was closely related to the symptom profiles of these patients (Kupper et al., 2010). In addition and above the mere amount of movement, the degree of synchrony between patients and healthy interactants may be indicative of various problems in the domain of interpersonal communication and social cognition. Methods: Based on our earlier study, head movement synchrony was assessed objectively (using Motion Energy Analysis, MEA) in 378 brief, videotaped role-play scenes involving 27 stabilized outpatients diagnosed with paranoid-type schizophrenia. Results: Lower head movement synchrony was indicative of symptoms (negative symptoms, but also of conceptual disorganization and lack of insight), verbal memory, patients’ self-evaluation of competence, and social functioning. Many of these relationships remained significant even when corrected for the amount of movement of the patients. Conclusion: The results suggest that nonverbal synchrony may be an objective and sensitive indicator of the severity of symptoms, cognition and social functioning.

How need for cognition affects the processing of achievement-related information

The present article analyzed, how need for cognition (NFC) influences the formation of performance expectancies. When processing information, individuals with lower NFC often rely on salient information and shortcuts compared to individuals higher in NFC. We assume that these preferences of processing will also make individuals low in NFC more responsive to salient achievement-related cues because the processing of salient cues is cognitively less demanding than the processing of non-salient cues. Therefore, individuals lower in NFC should tend to draw wider ranging inferences from salient achievement-related information. In a sample of N = 197 secondary school students, achievement-related feedback (grade on an English examination) affected changes in expectancies in non-corresponding academic subjects (e.g., expectation of final grade in mathematics or history) when NFC was lower, whereas for students with higher NFC, changes in expectancies in non-corresponding academic subjects were not affected.

High-school students' need for cognition, self-control capacity, and school achievement: testing a mediation hypothesis

In the present article, we examine the hypothesis that high-school students' motivation to engage in cognitive endeavors (i.e., their need for cognition; NFC) is positively related to their dispositional self-control capacity. Furthermore, we test the prediction that the relation between NFC and school achievement is mediated by self-control capacity. A questionnaire study with grade ten high-school students (N = 604) revealed the expected relations between NFC, self-control capacity, and school achievement. Sobel tests showed that self-control capacity mediated the relation between NFC and school grades as well as grade retention.

University and school students' motivation for effortful thinking: Factor structure, reliability, and validity of the German Need for Cognition Scale

Need for cognition (NFC) reflects a relatively stable trait regarding the degree to which one enjoys and engages in cognitive endeavors. We examined whether the previously demonstrated one-dimensional structure of the German NFC Scale could be replicated in three samples of undergraduates and secondary school students. Moreover, we investigated the test-retest reliability of the German NFC Scale, which has not yet been tested. Further, we investigated whether the scale would be valid in a sample of secondary school students. Multigroup confirmatory factor analyses established the one-dimensional factor structure of the long form as well as the short form of the German NFC Scale for undergraduates (N = 559), students of academic track secondary schools (German Gymnasium; N = 555), and students of vocational track secondary schools (German Realschule; N = 486). The scale proved to have a high test-retest reliability in a university student sample (N = 43). For secondary school students, we again found a high test-retest reliability (N = 157), and also found the scale to be valid (N = 181).

Passionate thinkers feel better: Self-control capacity as mediator of the relationship between need for cognition and affective adjustment

The present study tested a possible explanation for the positive relationship between the motivation to engage in cognitive endeavors (need for cognition, NFC) and indicators of affective adjustment (e.g., higher self-esteem, lower depression) that has been demonstrated in previous studies. We suggest that dispositional self-control capacity mediates this relationship, since NFC has been found to be related to self-control capacity, and self-control capacity is crucial for adjustment. NFC, dispositional self-control capacity, self-esteem, habitual depressive mood, and tendency to respond in a socially desirable manner were measured among 150 university students via self-report. Regression analyses and Sobel tests revealed that self-control capacity was a potential mediator of the positive relationship between NFC and affective adjustment. The findings were robust in terms of social desirability.

On the relationship between need for cognition and self-control capacity

In the present study, we examined the hypothesis that individuals’ motivational tendency to engage in effortful information processing (i.e., their need for cognition; NFC) is positively related to their self-control capacity. This hypothesis was based on previous findings that effortful information processing and self-control both depend on a joint strength resource, and that this resource is boosted by frequent use. NFC was assessed via questionnaire. One week later, the participants (N = 46) completed a test of self-control capacity (Stroop Task). As expected, NFC was positively related to self-control capacity but unrelated to general processing speed.

Prospective memory, executive functions, and metacognition are already differentiated in young elementary school children: Evidence from latent factor modelling

This study investigated the empirical differentiation of prospective memory, executive functions, and metacognition and their structural relationships in 119 elementary school children (M = 95 months, SD = 4.8 months). These cognitive abilities share many characteristics on the theoretical level and are all highly relevant in many everyday contexts when intentions must be executed. Nevertheless, their empirical relationships have not been examined on the latent level, although an empirical approach would contribute to our knowledge concerning the differentiation of cognitive abilities during childhood. We administered a computerized event-based prospective memory task, three executive function tasks (updating, inhibition, shifting), and a metacognitive control task in the context of spelling. Confirmatory factor analysis revealed that the three cognitive abilities are already empirically differentiable in young elementary school children. At the same time, prospective memory and executive functions were found to be strongly related, and there was also a close link between prospective memory and metacognitive control. Furthermore, executive functions and metacognitive control were marginally significantly related. The findings are discussed within a framework of developmental differentiation and conceptual similarities and differences.

Prospective Memory, Retrospective Memory, Executive Functions, and Metacognition: How they are linked longitudinally in young elementary school children

Succeeding in everyday activities often requires executive functioning (EF), metacognitive abilities (MC) and memory skills such as prospective memory (PM) and retrospective memory (RM). These cognitive abilities seem to gradually develop in childhood, possibly influencing each other during development. From a theoretical point of view, it is likely that they are closely interrelated, especially in children. Their empirical relation, however, is less clear. A model that links these cognitive abilities can help to better understand the relation between PM and RM and other cognitive processes. In this project we studied the longitudinal development of PM, RM, EF, and MC in 7-8 year old elementary school children across half a year. 119 second graders (MT1 = 95 months, SDT1, = 4.8 months) completed the same PM, RM, EF and MC tasks twice with a time-lag of 7 months. The developmental progression was analysed using paired t-tests, the longitudinal relationships were analysed using confirmatory factor analysis and all fit indices are in accordance with Hu and Bentler (1998). In general, performance improved significantly (ps < .001) and effect sizes ranged from .45 to .62 (Cohen’s d). CFA revealed a good model fit, c2(227, 119) = 242.56, p = .23, TLI = .973, CFI = .979, RMSEA = .024. At T1, significant cross-sectional links were found between PM T1 and RM T1, between PM T1 and EF T1, and between EF T1 and MC T1. Moreover, significant longitudinal links were found between EFT1 and PMT2 and between EFT1 and MCT2; EF T1 and RM T2 were marginally linked. Results underline previous findings showing that PM, RM, EF, and MC develop significantly during childhood, even within this short time period. Results also indicate that these cognitive abilities are linked not only cross-sectionally, but longitudinally. Most relevant, however, is the predictive role of EF for both metacognition and memory.

Longitudinal relationships between prospective memory, executive functions, and metacognition in young elementary school children

Prospective Memory (PM), executive functions (EF) and metacognition (MC) are relevant cognitive abilities for everyday functioning. They all seem to develop gradually in childhood and appear to be theoretically closely related; however, their empirical links remain unclear, especially in children. As a recent study revealed significant cross-sectional links between PM and EF, and a weaker but close link between PM and MC in 2nd graders (Spiess, Meier, & Roebers, submitted), this study focused on their short-term relationships and on their development. 119 children (MT1 =95 months, SDT1, = 4.8 months) completed the same tasks (one PM, three EF, one MC task) twice with a time-lag of 7 months. T-tests showed significant improvements in all tasks, except in the updating task. Different structural equation models were contrasted (AMOS); the best fitting model revealed that PMT2 was similarly predicted by PMT1 (r = .33) and EFT1 (r = .34). Additionally, EFT1 predicted MCT2 (r = .44), chi2(118, 119) = 128.91, p = .23, TLI = .968, CFI = .978, RMSEA = .028. Results show that PM, EF, and MC develop during childhood and also demonstrate that they are linked not only cross-sectionally, but longitudinally. Findings are discussed in a broader developmental framework.