APP23 mice as a model of Alzheimer's disease: an example of a transgenic approach to modeling a CNS disorder

Animal models are considered essential in research ensuing elucidation of human disease processes and subsequently, testing of potential therapeutic strategies. This is especially true for neurodegenerative disorders, in which the first steps in pathogenesis are often not accessible in human patients. Alzheimer's disease is vastly becoming a major medical and socioeconomic problem in our aging society. Valid animal models for this uniquely human condition should exhibit histopathological, biochemical, cognitive, and behavioral alterations observed in Alzheimer's disease patients. Major progress has been made since the understanding of the genetic basis of Alzheimer's disease and the development and improvement of transgenic mouse models. All present Alzheimer's disease models developed are partial but nevertheless essential in further unraveling the nature and spatial and temporal development of the complex molecular pathology underlying this condition. One of the more recent transgenic attempts to model Alzheimer's disease is the APP23 transgenic mouse. This article describes the development and assessment of this human amyloid precursor protein overexpression model. We summarize histopathological and biochemical, cognitive and behavioral observations made in heterozygous APP23 mice, thereby emphasizing the model's contribution to clarification of neurodegenerative disease mechanisms. In addition, the first therapeutic interventions in the APP23 model are included.     

Mood-congruent attentional bias in dysphoria: maintained attention to and impaired disengagement from negative information

Attentional bias to negative information has been proposed to be a cognitive vulnerability factor for the development of depression. In 2 experiments, the authors examined mood-congruent attentional bias in dysphoria. In both experiments, dysphoric and nondysphoric participants performed an attentional task with negative, positive, and neutral word cues preceding a target. Targets appeared either at the same or at the opposite location of the cue. Overall, results indicate that dysphoric participants show maintained attention for negative words at longer stimulus presentations, which is probably caused by impaired attentional disengagement from negative words. Furthermore, nondysphoric participants maintain their attention more strongly to positive words. These results are discussed in relation to recent developments in the pathogenesis and treatment of depression.     

Communication strategies to promote spiritual well-being among people with dementia

Declining communication skills in dementia threaten a person's sense of self. Building on enduring capabilities, pastoral visitors can significantly enhance spiritual well-being through the use of individualized, person-centered strategies. This article outlines the primary spiritual needs of older adults with dementia and some general strategies to improve communication based on enduring abilities. Detailed examples illustrate how these personhood-centered strategies can meet spiritual needs by connecting with individuals with dementia through life stories and through helping them to participate in religious life.     

Attention and inhibition in bilingual children: evidence from the dimensional change card sort task

In a previous study, a bilingual advantage for preschool children in solving the dimensional change card sort task was attributed to superiority in inhibition of attention (Bialystok, 1999). However, the task includes difficult representational demands to encode and interpret the task stimuli, and bilinguals may also have profited from superior representational abilities. This possibility is examined in three studies. In Study 1, bilinguals outperformed monolinguals on versions of the problem containing moderate representational demands but not on a more demanding condition. Studies 2 and 3 demonstrated that bilingual children were more skilled than monolinguals when the target dimensions were perceptual features of the stimulus and that the two groups were equivalent when the target dimensions were semantic features. The conclusions are that bilinguals have better inhibitory control for ignoring perceptual information than monolinguals do but are not more skilled in representation, confirming the results of the original study. The results also identify the ability to ignore an obsolete display feature as the critical difficulty in solving this task.     

Difficulties in comprehending causal relations among children with ADHD: the role of cognitive engagement

The present study examined whether time spent in long looks (i.e., >or=15 s), an index of cognitive engagement, would account for differences between children with attention deficit hyperactivity disorder (ADHD) and comparison children in understanding causal relations. Children viewed two televised stories, once in the presence of toys and once in their absence. Dependent variables were visual attention and questions tapping factual information and causal relations. Comparison children answered significantly more causal relations questions than did the children with ADHD, but only in the toys-present condition. Four lines of evidence revealed that the difficulties children with ADHD had in answering causal relations questions in the toys-present condition could be linked specifically to this group's decreased time spent in long looks.     

Functional analysis and treatment of inappropriate sexual behavior

The results of a functional analysis showed that inappropriate sexual behaviors exhibited by a 9-year-old boy who had been diagnosed with traumatic brain injury were maintained by positive reinforcement in the form of social attention. An intervention consisting of functional communication training and extinction resulted in reduced levels of inappropriate sexual behaviors.     

Project Trust: breaking down barriers between middle school children

This paper analyzes the success of a camp retreat weekend called Project Trust involving middle school students and teachers. The goal of the camp is to break down barriers between cliques identified as active in the school. The camp focuses on building team relationships across clique membership and incorporates elements of peace education and conflict resolution. A treatment group (campers) and comparison group (noncampers) were administered an adaptation of the Bogardus Social Distance Test and the Piers-Harris Children's Self-Concept Scale before and after the camp. Attendance was found to lower social distance scores for nine of the ten groups/cliques. Campers also had higher self-concept scores after the retreat.     

The relative strengths of indirect and direct word learning

Indirect word learning lacks many of the overt social-pragmatic cues to reference available in direct word learning, yet the two result in equally robust mappings when comprehension is assessed immediately after learning. The 3 studies reported here investigated how 3-year-olds (N=96) respond to more challenging tests of the relative strengths of indirect and direct word learning. In Study 1, children's comprehension of indirectly and directly learned proper and common names was tested after a 2-day delay. Both types of learning resulted in proper name mappings that picked out an individual and in common name mappings that could be extended to another category member. In Studies 2 and 3, children's comprehension was tested after they had been provided with additional, and sometimes inconsistent, information about the scope of previously learned words. There was a hint of a difference between indirect and direct word learning. but results overall suggested that the two were equivalent.     

Large-scale ensemble averaging of ambulatory impedance cardiograms

Impedance cardiography has been used increasingly to measure human physiological responses to emotional and mentally engaging stimuli. The validity of large-scale ensemble averaging of ambulatory impedance cardiograms was evaluated for preejection period (PEP), interbeat interval, and dZ/dt_(min) amplitude. We tested whether the average of “classical” 60-sec ensemble averages across periods with fixed activity, posture, physical load, social situation, and location could be accurately estimated from a single large-scale ensemble average spanning these entire periods. Impedance and electrocardiograms were recorded for about 24-h from 21 subjects. Recordings were scored by seven raters, using both methods for each subject. Good agreement (average intraclass correlation coefficient was .91) between both ensemble averaging methods was found for all three cardiac function measures. The results indicate that for unambiguous ambulatory impedance cardiograms, large-scale ensemble averaging is valid, which makes measuring prolonged changes in cardiac sympathetic activity by measuring ambulatory PEP feasible even in large epidemiological samples.     

Acquired ‘theory of mind'' impairments following stroke

The ability to attribute thoughts and feelings to self and others (‘theory of mind') has been hypothesised to have an innate neural basis and a dedicated cognitive mechanism. Evidence in favour of this proposal has come from autism; a brain-based developmental disorder which appears to be characterised by impaired theory of mind, despite sometimes good general reasoning skills/IQ. To date no case of specific acquired theory of mind impairment has been reported. The present study examined theory of mind in adults who had suffered right hemisphere stroke, a group known to show pragmatic and social difficulties. In one study using story materials and two using cartoons, patients' understanding of materials requiring attribution of mental states (e.g. ignorance, false belief) was significantly worse than their understanding of non-mental control materials. Data from healthy elderly subjects, and a small group of left hemisphere patients (who received the tasks in modified form), suggest that this impairment on mental state tasks is not a function of task difficulty. The findings support the notion of a dedicated cognitive system for theory of mind, and suggest a role for the healthy right hemisphere in the attribution of mental states.