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.     

Structure and stimulus familiarity: a study of memory in chess-players with functional magnetic resonance imaging

A grandmaster and an international chess master were compared with a group of novices in a memory task with chess and non-chess stimuli, varying the structure and familiarity of the stimuli, while functional magnetic resonance images were acquired. The pattern of brain activity in the masters was different from that of the novices. Masters showed no differences in brain activity when different degrees of structure and familiarity where compared; however, novices did show differences in brain activity in such contrasts. The most important differences were found in the contrast of stimulus familiarity with chess positions. In this contrast, there was an extended brain activity in bilateral frontal areas such as the anterior cingulate and the superior, middle, and inferior frontal gyri; furthermore, posterior areas, such as posterior cingulate and cerebellum, showed great bilateral activation. These results strengthen the hypothesis that when performing a domain-specific task, experts activate different brain systems from that of novices. The use of the experts-versus-novices paradigm in brain imaging contributes towards the search for brain systems involved in cognitive processes.     

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.     

Weathering the storm: children's long-term recall of Hurricane Andrew

Children who experienced a highly stressful natural disaster, Hurricane Andrew, were interviewed within a few months of the event, when they were 3-4 years old, and again 6 years later, when they were 9-10 years old. Children were grouped into low, moderate, or high stress groups depending on the severity of the experienced storm. All children were able to recall this event in vivid detail 6 years later. In fact, children reported over twice as many propositions at the second interview as at the first. At the initial interview, children in the high stress group reported less information than children in the moderate stress group, but 6 years later, children in all three stress groups reported similar amounts of information. However children in the high stress group needed more questions and prompts than children in the other stress groups. Yet children in the high stress group also reported more consistent information between the two interviews, especially about the storm, than children in the other stress groups. Implications for children's developing memory of stressful events are discussed.     

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.     

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.     

Parent-adolescent relations and adolescent functioning: self-esteem, substance abuse, and delinquency

The present study examined parental support and monitoring as they relate to adolescent outcomes. It was hypothesized that support and monitoring would be associated with higher self-esteem and less risky behavior during adolescence. The diverse sample included 16,749 adolescents assessed as part of the National Educational Longitudinal Study. Both high parental support and parental monitoring were related to greater self-esteem and lower risk behaviors. The findings partially confirm, as well as extend, propositions in attachment theory.     

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.