In this thesis, we have used the kernel based orthogonal projection to latent structures (K-OPLS) method to discriminate between Alzheimer's Disease patients (AD) and healthy control subjects (CTL), and to predict conversion from mild cognitive impairment (MCI) to AD. In this regard three cohorts were used to create two different datasets; a small dataset including 63 subjects based on the Alzheimer’s Research Trust (ART) cohort and a large dataset including 1074 subjects combining the AddNeuroMed (ANM) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts. In the ART dataset, 34 regional cortical thickness measures and 21 volumetric measures from MRI in addition to 3 metabolite ratios from MRS, altogether 58 variables obtained for 28 AD and 35 CTL subjects. Three different K-OPLS models were created based on MRI and MRS measures and their combination. Combining the MRI and the MRS measures significantly improved the discriminant power resulting in a sensitivity of 96.4% and a specificity of 97.1%. In the combined dataset (ADNI and AddNeuroMed), the Freesurfer pipeline was utilized to extract 34 regional cortical thickness measures and 23 volumetric measures from MRI scans of 295 AD, 335 CTL and 444 MCI subjects. The classification of AD and CTL subjects using the K-OPLS model resulted in a high sensitivity of 85.8% and a specificity of 91.3%. Subsequently, the K-OPLS model was used to prospectively predict conversion from MCI to AD, according to the one year follow up diagnosis. As a result, 78.3% of the MCI converters were classified as AD-like and 57.5% of the MCI non-converters were classified as control-like. Furthermore, an age correction method was proposed to remove the effect of age as a confounding factor. The age correction method successfully removed the age-related changes of the data. Also, the age correction method slightly improved the performance regarding to classification and prediction. This resulted in that 82.1% of the MCI converters were correctly classified. All analyses were performed using 7-fold cross validation. The K-OPLS method shows strong potential for classification of AD and CTL, and for prediction of MCI conversion.

Individuals with mild cognitive impairment (MCI) show variable impairment in autobiographical memory function, source memory function and reduced integrity in the brain’s default mode network (DMN). There is overlap between the DMN, such as the medial posterior cortical hub, and brain regions that are active when participants recall autobiographical memories. To assess the association between autobiographical memory and the DMN, 14 MCI and eleven age and education-matched healthy control participants were assessed using the autobiographical memory interview (AMI) and underwent resting state fMRI scans. The same participants underwent a test of source memory which assessed both recognition and source memory. The MCI group showed significantly increased semantic as well episodic memory impairments using the AMI, evident across the lifespan for episodic memory but not for childhood semantic memory. Significantly poorer DMN connectivity, using a goodness of fit index (GOF) of the DMN template, was evident in the MCI group. MCI participants showed poorer performance on both recognition and source memory relative to HC participants. A modest association between AMI semantic memory (r=0.4) scores, but not episodic memory scores (r=0.09), and DMN connectivity was found in these participants. For future study the predictive value of MR imaging in the DMN of MCI participants should be explored.

Background: Mild Cognitive Impairment (MCI) is a clinical construct reputed to represent an intermediate stage on a continuum between normal aging and cognitive decline. Conceptual and prognostic ambiguity can lead to significant diagnostic challenges and there is a need for accurate screening tests which can assist clinicians with decision-making. A diagnosis of MCI is also associated with considerable uncertainty for patients who may be adjusting to cognitive difficulties along with an increased risk of developing dementia. Beliefs about MCI may influence psychosocial adjustment, and individual differences in ‘psychological flexibility (PF)’, as conceptualised by the Acceptance and Commitment Therapy (ACT) model, may also be involved in this process. Objectives: In order to evaluate the accuracy and clinical utility of a recently developed screening tool for MCI, the Montreal Cognitive Assessment (MoCA), a systematic review of validation and diagnostic test accuracy (DTA) studies for this measure was conducted. Psychosocial adjustment to a diagnosis of MCI was also a key focus. An empirical study was therefore carried out with the aim of evaluating the possible relationships between cognitive impairment, illness representations about MCI, psychological wellbeing and quality of life (QoL), and to assess the potential involvement of PF. Method: Following a systematic search of relevant electronic databases and reference lists, validation and DTA studies of the MoCA were identified and evaluated for methodological quality. For the empirical study, patients recently diagnosed with MCI were recruited from local NHS memory clinic services and completed the MoCA and a questionnaire pack assessing illness representations, PF, mood, anxiety and QoL. Results: The systematic review identified 18 validation and DTA studies. Few of the studies achieved high ratings for methodological quality and problems with representativeness and generalisability were identified. Nevertheless, sensitivity levels appeared robust across studies, though specificity was variable. For the present empirical study, participants reported a spectrum of positive and negative beliefs about MCI. Distress attributed to MCI was associated with anxiety, along with perceptions of more serious illness consequences, while higher PF was associated with higher perceived QoL and mood. Lived experience of MCI appeared to have more relevance to psychosocial adjustment than objective cognitive impairment. Conclusions: The results of the systematic review indicate that while the MoCA is a robust tool overall in the identification of cognitive impairment, estimates of accuracy may be exaggerated by inter-study variation and bias. More rigorous validation studies are therefore needed. Implications for clinical decision-making regarding MCI are discussed and recommendations for future accuracy studies are outlined. The empirical study supported the findings of previous studies of the relevance of illness representations to psychosocial adjustment in MCI and added to the evidence base by providing preliminary support for the possible involvement of PF. The results suggest that both cognitive content and PF may represent possible vehicles for therapeutic change in patients with adjustment difficulties, and indicate that further investigation of these factors is warranted. Conclusions are limited, however, by small sample size and low statistical power. Replication of these findings with a larger and more representative sample is therefore recommended.

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This thesis presents research investigating objectively and subjectively examined cognitive impairment in Bipolar Disorder (BD) in comparison to disorders with similar cognitive symptomatologies. First, a systematic review and meta-analyses compared the cognitive performance between BD and Mild Cognitive Impairment (MCI) or dementia. Studies included in this review and meta-analyses assessed cognitive performances using multiple objective cognitive assessments. Results from these meta-analyses found greater impairment in BD relative to MCI on motor initiative abilities. Additionally, there were similarities in cognitive deficits on delayed memory recall and visuoconstructional abilities between BD and MCI. For the comparison between BD and dementia, we analyzed the findings of studies comparing BD across different mood states with different types of dementia, where BD in acute mood episode demonstrated greater deficits in attention, working memory, verbal memory, and executive function than behavioral variant frontotemporal dementia (bvFTD). In contrast, overall cognitive functioning and verbal fluency was more impaired in Alzheimer’s disease (AD) in comparison to BD during euthymia. Next, we shifted the focus on examining subjective cognitive complaints in BD relative to Major Depressive Disorder (MDD). Our study is unique from previous literature with the same aim considering that it only involved patients recently diagnosed with BD, and subjective complaints were assessed with the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA), an instrument specific to cognitive complaints detected in BD. The findings demonstrate higher subjective cognitive complaints in euthymic BD in comparison to euthymic MDD, suggesting greater self-perceived difficulties in BD, even in the beginning of the illness. Taken together, findings from the studies presented in this thesis highlight the importance of early detection and intervention of cognitive impairments in BD, with the aim of enhancing cognitive abilities, and prevention of further cognitive degradation with the progression of the disorder / Thesis / Master of Science (MSc)

In 1997 the Management Charter Initiative (MCI) officially launched the new Management NVQs (National Vocational Qualifications), benchmarks which attempted to describe the work performed by British managers. This article is a review of those qualifications. It remembers some of the main problems associated with the original Management NVQs and, drawing on some of the best theoretical and empirical accounts of managerial work, argues that the new qualifications have failed to live up to the MCI¿s original promise, to assist the development and training of managers.

The theoretical part explains terms such as environment, atmosphere and climate in the class. It deals with the social climate and all factors shaping it, i.e. with the teacher, the schoolchild, parents and the school environment. The next part of the theoretical work is devoted to the class as a social group and to small class schools and their specialties. Furthermore ? there is stated an overview of teaching methods used at the first stage of the elementary school on. The practical part is focused on a research of social climate in the classes of the small-class schools from the teachers´ and schoolchildren´ perspective. The respondents were schoolchildren of the four classes and their teachers. The methods used: a standardized questionnaire "My Class Inventory", observation and interview. The results are presented in tables and graphs, completed with comments. There are also mentioned positives and negatives of the grades, which are joined into one classroom and the teaching methods used in small class schools.

My thesis coucerns in a level of a climate among the schoolmates in the 5. class in the small school and subsequently in the 6. class in the fully organized primary school. The climate was compared by the same scholars during two classes. The sample coucerns in 3 classes in the small schools in the villages in the surroundings of Jindřichův Hradec and 3 classes in the fully organized schools in the Down. In the practical part was used a questionnaire MCI, specifically, his current form. Aime of a thesis was to find out which chmate there is in the small schools, if the participants further work with this situation and, finály, whether the chmate ganges with a transfer the pupils into a fully organized primary school.