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.

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.

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.

Volatiles produced by soil-borne endophytic bacteria increase plant pathogen resistance and affect tritrophic interactions

Volatile organic compounds (VOCs) released by soil microorganisms influence plant growth and pathogen resistance. Yet, very little is known about their influence on herbivores and higher trophic levels. We studied the origin and role of a major bacterial VOC, 2,3-butanediol (2,3-BD), on plant growth, pathogen and herbivore resistance, and the attraction of natural enemies in maize. One of the major contributors to 2,3-BD in the headspace of soil-grown maize seedlings was identified as Enterobacter aerogenes, an endophytic bacterium that colonizes the plants. The production of 2,3-BD by E. aerogenes rendered maize plants more resistant against the Northern corn leaf blight fungus Setosphaeria turcica. On the contrary, E. aerogenes-inoculated plants were less resistant against the caterpillar Spodoptera littoralis. The effect of 2,3-BD on the attraction of the parasitoid Cotesia marginiventris was more variable: 2,3-BD application to the headspace of the plants had no effect on the parasitoids, but application to the soil increased parasitoid attraction. Furthermore, inoculation of seeds with E. aerogenes decreased plant attractiveness, whereas inoculation of soil with a total extract of soil microbes increased parasitoid attraction, suggesting that the effect of 2,3-BD on the parasitoid is indirect and depends on the composition of the microbial community.

Internal Models, Vestibular Cognition, and Mental Imagery: Conceptual Considerations

Vestibular cognition has recently gained attention. Despite numerous experimental and clinical demonstrations, it is not yet clear what vestibular cognition really is. For future research in vestibular cognition, adopting a computational approach will make it easier to explore the underlying mech- anisms. Indeed, most modeling approaches in vestibular science include a top-down or a priori component. We review recent Bayesian optimal observer models, and discuss in detail the conceptual value of prior assumptions, likelihood and posterior estimates for research in vestibular cognition. We then consider forward models in vestibular processing, which are required in order to distinguish between sensory input that is induced by active self-motion, and sensory input that is due to passive self-motion. We suggest that forward models are used not only in the service of estimating sensory states but they can also be drawn upon in an offline mode (e.g., spatial perspective transformations), in which interaction with sensory input is not desired. A computational approach to vestibular cogni- tion will help to discover connections across studies, and it will provide a more coherent framework for investigating vestibular cognition.

Effects of subthalamic nucleus stimulation on cognition and mood in Parkinson’s disease (PD)

Objective: To assess the neuropsychological outcome as a safety measure and quality control in patients with subthalamic nucleus (STN) stimulation for PD. Background: Deep brain stimulation (DBS) is considered a relatively safe treatment used in patients with movement disorders. However, neuropsychological alterations have been reported in patients with STN DBS for PD. Cognition and mood are important determinants of quality of life in PD patients and must be assessed for safety control. Methods: Seventeen consecutive patients (8 women) who underwent STN DBS for PD have been assessed before and 4 months after surgery. Besides motor symptoms (UPDRS-III), mood (Beck Depression Inventory, Hamilton Depression Rating Scale) and neuropsychological aspects, mainly executive functions, have been assessed (mini mental state examination, semantic and phonematic verbal fluency, go-no go test, stroop test, trail making test, tests of alertness and attention, digit span, wordlist learning, praxia, Boston naming test, figure drawing, visual perception). Paired t-tests were used for comparisons before and after surgery. Results: Patients were 61.6±7.8 years old at baseline assessment. All surgeries were performed without major adverse events. Motor symptoms ‘‘on’’ medication remained stable whereas they improved in the ‘‘off’’ condition (p<0.001). Mood was not depressed before surgery and remained unchanged at follow-up. All neuropsychological assessment outcome measures remained stable at follow-up with the exception of semantic verbal fluency and wordlist learning. Semantic verbal fluency decreased by 21±16% (p<0.001) and there was a trend to worse phonematic verbal fluency after surgery (p=0.06). Recall of a list of 10 words was worse after surgery only for the third attempt of recall (13%, p<0.005). Conclusions: Verbal fluency decreased in our patients after STN DBS, as previously reported. The procedure was otherwise safe and did not lead to deterioration of mood.

Cognition and Student Learning Through the Arts

An increasing number of recent research studies suggest connections between cognition, social and emotional development, and the arts. Some studies indicate that students in schools where the arts are an integral part of the academic program tend to do better in school than those students where that is not the case. This study examines home/school factors that contribute most to variance in student learning and achievement and the arts from over 8,000 students in grade 5. The findings suggest in-school arts programs may have less of an impact on student achievement than proposed by previous research.

Intervening to reach adolescents and affect health

Background. Assessing the health status of adolescents is challenging for health care providers. Personal disclosure has been associated with improved health outcomes. Story-centered care was examined as an intervention for promoting adolescent disclosure during an urgent care visit. ^ Objectives. This study explored: (1) the effectiveness of story-centered care for promoting adolescent disclosure; (2) health-associated words used by adolescents to describe pressing concerns after an urgent care visit when they had standard care (SC) or story-centered care (SCC) conducted by a Nurse Practitioner (NP). ^ Methods. Subjects were randomly assigned to SC or SCC. In SC, adolescent presenting concerns were identified and treated. In SCC, presenting concerns were treated and NP-adolescent dialogue, facilitated through a screening tool, queried matters of importance to adolescent life. After the visit, adolescents wrote about pressing concerns for 15 minutes. Written words were analyzed with Linguistic Inquiry and Word Count, a software program for analyzing narrative. Ratios were calculated for the number of words (adolescent: NP) used during the urgent care visit. Analysis of variance (ANOVA) was used to evaluate gender-intervention differences in health-associated words. ^ Results. One hundred and six adolescents [Hispanic (65%), White (35%)] completed the study. Fifty-five were female; the average age was 17 (sd = 2.1) years. ^ Adolescents in the story intervention used more words (adolescent: NP, 1:1.3) than those in standard intervention (adolescent: NP, 1:2.7) in proportion to the number of words used by the NP during the urgent care visit. There were gender-intervention differences (p < .01) in positive emotion words and past-tense words in writings about pressing concerns. Males who received the story intervention used more positive emotion and less past-tense words than adolescent males with standard care. Females used more social words (p < .01) in their writings regardless of intervention group. ^ Conclusion. SCC enhanced adolescent disclosure during an urgent care visit. Adolescents will talk to health care providers during episodic visits and males may benefit more than girls may from this approach. Evidence suggests there is value in attending to both presenting and pressing concerns of adolescents. ^