3 research outputs found
Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States
No full textß-amyloid (Aß) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here we explored potential relationships between functional connectivity patterns within the default-mode network (DMN), age, CSF biomarkers (Aß42 and pTau181) and cognitive status in older adults. Multiple measures of functional connectivity were explored including a novel time series based measure (Total Interdependence; TI). In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aß42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of functional connectivity in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults
Investigation into factors associated with the provision of effective education for children with autistic spectrum disorders
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis investigates the factors associated with provision of education for children with autism spectrum disorders. The child is at the centre of this investigation, as the issues and constraints clearly impact on the quality of the provision delivered. Educational provision for children with autism also affects families and social agencies. The family is usually first to recognise that their child is not developing as he or she should. Typically, a diagnosis of autism or autistic spectrum disorder leads the family to the LEA in an effort to get the child's educational needs met within a school setting.
Improvement in educational provision for children can only be obtained when it is based on research in this area. This is especially true for the case of children diagnosed with autism, as research is limited. What research does exist focuses on specific methodologies or proposed causes, and does not explore the effects that appropriate provision has on a child.
To aid this thesis, systems theory has been employed to explore the tensions and dilemmas that exist. This ecosystemic approach is useful when teasing apart the influences both proximal and distal that benefit the child's educational experience. These influences can come from the school, home, LEA or the interactions between and among these partners. This study will examine these influences. Through the use of a case study, the researcher observed a school during its day-to-day implementation of educational provision. In addition, the views of an LEA and parents were sought through the use of interviews and a survey.
The main research findings showed several factors as having influence on the child in regards to educational provision. Investigation into a school showed the difficulties associated with putting provision into practice. When faced with severe staffing shortages, absence of active leadership,, and extreme behavioural problems of the children, teaching activity was thwarted. Survey results revealed the difficulties faced by parents in securing provision. Parents reported high levels of stress that this research correlated to longer waiting times, late diagnosis, type of provision, and guidance from specialists. Significant also, was the finding that survey parents reported a statistically significant decrease in the age of diagnosis of the children. Significant findings revealed through LEA interviews found that although striving to work with families, efforts were frustrated by increasing numbers of children, limitations on the number of children accepted into favoured placements, and parental self imposed restrictions on placement choice.
Lastly, this research proposed several key suggestions based on the literature review and the research undertaken to improve and promote best practice in the agreement, allocation and enactment of educational provision
Role of environmental confounding in the association between FKBP5 and first-episode psychosis
No full textBackground: Failure to account for the etiological diversity that typically occurs in psychiatric cohorts may increase the potential for confounding, as a proportion of genetic variance will be specific to exposures that have variable distribution in cases. This study investigated whether minimizing the potential for such confounding strengthened the evidence for a genetic candidate currently unsupported at the genome-wide level.Methods: 291 first-episode psychosis cases from South London UK, and 218 unaffected controls were evaluated for a functional polymorphism at the rs1360780 locus in FKBP5. The relationship between FKBP5 and psychosis was modelled using logistic regression. Cannabis use (Cannabis Experiences Questionnaire) and parental separation (Childhood Experience of Care and Abuse Questionnaire) were modelled as confounders in the analysis.Results: Association at rs1360780 was not detected until the effects of the two environmental factors had been adjusted for in the model (OR=2.81, 95% CI 1.23-6.43, p=0.02). A statistical interaction between rs1360780 and parental separation was confirmed by stratified tests (OR=2.8, p=0.02 vs. OR=0.89, p=0.80). The genetic main effect was directionally-consistent with findings in other (stress-related) clinical phenotypes. Moreover, the variation in effect magnitude was explained by the level of power associated with different cannabis constructs used in the model (r=0.95).Conclusions: Our results suggest that the extent to which genetic variants in FKBP5 can influence susceptibility to psychosis may depend on the other etiological factors involved. This finding requires further validation in other large independent cohorts. Potentially this work could have translational implications, as the ability to discriminate between genetic etiologies, based on a case-by-case understanding of exposure history would confer an important clinical advantage that would benefit the delivery of personalizable treatment strategie
