Identification and characterization of a new class of cognitive enhancers based on inhibition of insulin-regulated aminopeptidase

Approximately one-quarter of people over the age of 65 are estimated to suffer some form of cognitive impairment, underscoring the need for effective cognitive-enhancing agents. Insulin-regulated aminopeptidase (IRAP) is potentially an innovative target for the development of cognitive enhancers, as its peptide inhibitors exhibit memory-enhancing effects in both normal and memory-impaired rodents. Using a homology model of the catalytic domain of IRAP and virtual screening, we have identified a class of nonpeptide, small-molecule inhibitors of IRAP. Structure-based computational development of an initial "hit" resulted in the identification of two divergent families of compounds. Subsequent medicinal chemistry performed on the highest affinity compound produced inhibitors with nanomolar affinities (Ki 20–700 nM) for IRAP. In vivo efficacy of one of these inhibitors was demonstrated in rats with an acute dose (1 nmol in 1 µl) administered into the lateral ventricles, improving performance in both spatial working and recognition memory paradigms. We have identified a family of specific IRAP inhibitors that is biologically active which will be useful both in understanding the physiological role of IRAP and potentially in the development of clinically useful cognitive enhancers. Notably, this study also provides unequivocal proof of principal that inhibition of IRAP results in memory enhancement.

Identifying multi-view patterns with hierarchy and granularity based multimodal (HGM) cognitive model

Humans perceive entities such as objects, patterns, events, etc. as concepts, which are the basic units in human intelligence and communications. In addition, perceptions of these entities could be abstracted and generalised at multiple levels of granularity. In particular, such granulation allows the formation and usage of concepts in human intelligence. Such natural granularity in human intelligence could inspire and motivate the design and development of pattern identification approach in Data Mining. In our opinion, a pattern could be perceived at multiple levels of granularity and thus we advocate for the co-existence of hierarchy and granularity. In addition, granular patterns exist across different sources of data (multimodality). In this paper, we present a cognitive model that incorporates the characteristics of Hierarchy, Granularity and Multimodality for multi-view patterns identification in crime domain. Such framework is implemented with Growing Self Organising Maps (GSOM) and some experimental results are presented and discussed.

Design of a valid simulation for researching physical, physiological and cognitive performance in volunteer firefighters during bushfire deployment.

Every year, Australian firefighters protect our nation from the devastation of bushfire. Understanding the impact of consecutive long shifts in hot, smoky conditions is essential for making decisions during campaign fires. At present, the evidence-base for such decisions is limited to laboratory studies with little relevance to bushfire suppression or field research where the impact of environmental and workload stressors cannot be measured. To counter these limitations, we have developed a three-day simulation that mimics the work and environment of campaign bushfire suppression. Construction of the simulation involved three stages; 1) data collection and analysis; 2) design and development; and 3) trial and refinement. The frequency, intensity, duration and type of physical work performed on the fireground is well documented and a modified applied cognitive task analysis, using experienced firefighters was used as a framework to describe in detail the non-physical aspects of the work. The design and development of the simulation incorporated the physical and non-physical aspects of the work into simulated tasks. Finally, experienced firefighters participated in trials of the simulation and reviewed digital recordings to ensure that the simulation accurately represented campaign bushfire suppression work. The outcome of this project is a valid, realistic, and reliable simulation of the physiological, physical and cognitive aspects of a volunteer firefighter on a three-day bushfire deployment.

Cognitive intervention in autism using multimedia stimulus

We demonstrate an open multimedia-based system for delivering early intervention therapy for autism. Using exible multi-touch interfaces together with principled ways to access rich content and tasks, we show how a syllabus can be translated into stimulus sets for early intervention. Media stimuli are able to be presented agnostic to language and media modality due to a semantic network of concepts and relations that are fundamental to language and cognitive development, which enable stimulus complexity to be adjusted to child performance. Being open, the system is able to assemble enough media stimuli to avoid children over-learning, and is able to be customised to a specific child which aids with engagement. Computer-based delivery enables automation of session logging and reporting, a fundamental and time-consuming part of therapy.

Total antioxidant status correlates with cognitive impairment in patients with recurrent depressive disorder

Depressive disorder is a multifactorial diseases, that one of the typical feature are cognitive impairments. The aim of this study was to determine the total antioxidant status (TAS) in patients with recurrent depressive disorder (rDD) and to define relationship between plasma levels of TAS and the cognitive performance. Design and methods: the study comprised 74 subjects: patients with rDD (n = 45) and healthy subjects (n = 29). Cognitive function assessment was based on: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Statistically significant differences were found in the intensity of depression symptoms, measured by the Hamilton Depression Rating Scale (HDRS) on therapy onset versus the examination results after 8 weeks of treatment (p < 0.001). The level of TAS was substantially higher in patients with rDD (p = 0.01). For rDD patients, elevated TAS levels were associated with worse cognitive test performance. The higher was the concentration of plasma TAS, the greater was the severity of depressive symptoms measured by HDRS before and after pharmacotherapy. (1) Higher concentration of plasma TAS in rDD patients is associated with the severity of depressive symptoms. (2) Elevated levels of plasma TAS are related to impairment of short-term declarative memory, long-term declarative-memory, verbal fluency and working memory.

Putting the cog into cognitive : the theory behind teaching practice.

During teacher education programs, lecturers introduce students to the joys of studying a range of theorists. Sadly, many teachers appear to put theoretical perspectives of practice behind them immediately the essay-writing is over. The purpose of this paper is to breathe life into the work of theorist, relevant to early childhood teaching. I aim to inspire teachers to gain a new depth of satisfaction from their teaching as they critically reflect on their practice and gain a deeper understanding of teaching strategies that support children’s learning and development.

Does the cognitive interview promote the coherence of narrative accounts in children with and without an intellectual disability?

We examined whether the cognitive interview (CI) procedure enhanced the coherence of narrative accounts provided by children with and without intellectual disabilities (ID), matched on chronological age. Children watched a videotaped magic show; one day later, they were interviewed using the CI or a structured interview (SI). Children interviewed using the CI reported more correct details than those interviewed using the SI. Additionally, children interviewed using the CI reported more contextual background details, more logically ordered sequences, more temporal markers, and fewer inconsistencies in their stories than those interviewed using the SI. However, the CI did not increase the number of story grammar elements compared with the SI. Overall children interviewed with the CI told better stories than those interviewed with the SI. This finding provided further support for the effectiveness of the CI with vulnerable witnesses, particularly children with ID.

Assessing the effectiveness of the cognitive interview for children with severe intellectual disabilities

We examined whether the cognitive interview (CI) procedure increased event recall in children with severe intellectual disabilities (ID) compared with children with no ID. Forty-six children with and without ID watched a videotaped event; they were aged between eight and 11 years. The next day they were individually interviewed using the CI or a structured interview (SI). Interviews consisted of free recall and specific questions, some of which contained leading or misleading information. The leading and misleading questions determined children’s susceptibility to information presented after the event. Overall, children without ID reported more correct information than children with ID. For all children, the CI led to more correct recall than the SI without increases in incorrect details or confabulations. Although the CI did not decrease children’s susceptibility to the misleading questions compared with the SI, children without ID disagreed with more of the misleading suggestions than children with ID. These results suggest that the CI may indeed be a valuable tool to elicit information from very vulnerable witnesses.

Effects of N-acetyl cysteine on cognitive function in bipolar disorder

Aims

Bipolar disorder is characterized by progressive changes in cognition with declines in executive functioning, memory and sustained attention. Current pharmacotherapies for bipolar disorder target mood symptoms but have not addressed these cognitive changes resulting in euthymic individuals who still experience cognitive deficits. N-acetyl cysteine (NAC) has been shown to have effects on antioxidant status, glutamate transmission, inflammation and neurogenesis. Adjunctive treatment with NAC improves the symptoms experienced by those with bipolar disorder, particularly depression, and it was hypothesized that cognition may also be improved following NAC treatment.
Methods

As part of a larger randomized, double-blind, placebo-controlled trial, participants in the current report were tested at baseline and 6 months to assess changes in cognitive function following either 2000 mg of NAC daily or placebo.
Results

This study failed to find changes in cognitive function following treatment with NAC compared to placebo.
Conclusions

While an important pilot study, this study had a small sample size and included a limited battery of cognitive tests. Further investigations on the effects of NAC on cognitive performance in bipolar disorder are required.