| 1. |
- Brusini, Irene
(författare)
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Methods for the analysis and characterization of brain morphology from MRI images
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Brain magnetic resonance imaging (MRI) is an imaging modality that produces detailed images of the brain without using any ionizing radiation. From a structural MRI scan, it is possible to extract morphological properties of different brain regions, such as their volume and shape. These measures can both allow a better understanding of how the brain changes due to multiple factors (e.g., environmental and pathological) and contribute to the identification of new imaging biomarkers of neurological and psychiatric diseases. The overall goal of the present thesis is to advance the knowledge on how brain MRI image processing can be effectively used to analyze and characterize brain structure.The first two works presented in this thesis are animal studies that primarily aim to use MRI data for analyzing differences between groups of interest. In Paper I, MRI scans from wild and domestic rabbits were processed to identify structural brain differences between these two groups. Domestication was found to significantly reshape brain structure in terms of both regional gray matter volume and white matter integrity. In Paper II, rat brain MRI scans were used to train a brain age prediction model. This model was then tested on both controls and a group of rats that underwent long-term environmental enrichment and dietary restriction. This healthy lifestyle intervention was shown to significantly affect the predicted brain age trajectories by slowing the rats' aging process compared to controls. Furthermore, brain age predicted on young adult rats was found to have a significant effect on survival.Papers III to V are human studies that propose deep learning-based methods for segmenting brain structures that can be severely affected by neurodegeneration. In particular, Papers III and IV focus on U-Net-based 2D segmentation of the corpus callosum (CC) in multiple sclerosis (MS) patients. In both studies, good segmentation accuracy was obtained and a significant correlation was found between CC area and the patient's level of cognitive and physical disability. Additionally, in Paper IV, shape analysis of the segmented CC revealed a significant association between disability and both CC thickness and bending angle. Conversely, in Paper V, a novel method for automatic segmentation of the hippocampus is proposed, which consists of embedding a statistical shape prior as context information into a U-Net-based framework. The inclusion of shape information was shown to significantly improve segmentation accuracy when testing the method on a new unseen cohort (i.e., different from the one used for training). Furthermore, good performance was observed across three different diagnostic groups (healthy controls, subjects with mild cognitive impairment and Alzheimer's patients) that were characterized by different levels of hippocampal atrophy.In summary, the studies presented in this thesis support the great value of MRI image analysis for the advancement of neuroscientific knowledge, and their contribution is mostly two-fold. First, by applying well-established processing methods on datasets that had not yet been explored in the literature, it was possible to characterize specific brain changes and disentangle relevant problems of a clinical or biological nature. Second, a technical contribution is provided by modifying and extending already-existing brain image processing methods to achieve good performance on new datasets.
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| 2. |
- Lövheim, Hugo, 1981-
(författare)
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Psychotropic and analgesic drug use among old people : with special focus on people living in institutional geriatric care
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Old people in general, and those affected by dementia disorders in particular, are more sensitive to drug side effects than younger people. Despite this, the use of nervous system drugs and analgesics among old people is common, and has increased in recent years.Institutional geriatric care accommodates people who need round-the-clock supervision and care, due to somatic, psychiatric, cognitive or behavioral symptomatology. A majority of those living in institutional geriatric care suffers from dementia disorders.This thesis is based on three different data collections. Two large cross-sectional studies, the AC1982 and AC2000 data collections, including all those living in institutional geriatric care in the county of Västerbotten in May 1982 and 2000 respectively (n=3195 and n=3669) and one study, the GERDA/Umeå 85+ data collection, including a sample of very old people, living at home and in institutions (n=546), in the municipalities of Umeå, Sweden and Vaasa and Mustasaari, Finland, in 2005-2006.The use of psychotropic drugs and analgesics was common among old people living in geriatric care and among very old people in general. A higher proportion of people with dementia received certain nervous system drugs, such as antipsychotic drugs. The use of antipsychotic drugs among people with cognitive impairment living in geriatric care was found to be correlated to several behaviors and symptoms that are not proper indications for antipsychotic drug use, and also factors related more to the staff and the caring situation.Over the course of eighteen years, from 1982 to 2000, there has been a manifold increase in the use of antidepressants, anxiolytics and hypnotics in geriatric care, but the use of antipsychotics had decreased slightly. During the same time, the prevalence of several depressive symptoms decreased significantly, correcting for demographical changes. One analysis of calculated numbers needed to treat, however, indicated poor remission rates, suggesting that even better results might be achievable. The prevalence of depressive symptoms among people with moderate cognitive impairment remained unchanged between 1982 and 2000, despite the fact that about 50% were receiving treatment with antidepressants in 2000. One possible explanation might be that depressive symptoms have different etiologies in different stages of a dementia disorder.Approximately a quarter of the people experiencing pain in geriatric care were not receiving any regular analgesic treatment. One possible reason might be misconceptions among the caring staff regarding whether or not the residents were receiving analgesic treatment. Such misconceptions were found to be common.In conclusion, psychotropic and analgesic drug use among old people in geriatric care, and very old people in general, was found to be common and in many cases possibly inappropriate. The use of antipsychotics among people with dementia deserves particular concern, because of the high risk of severe adverse events and the limited evidence for positive effects. The use of antidepressants, on the other hand, might have contributed to a lower prevalence of depressive symptoms among old people.
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| 3. |
- Nägga, Katarina, 1962-
(författare)
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Aspects on clinical diagnosis of dementia, with focus on biological markers
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The clinical dementia diagnosis has become more complex with increasing knowledge of the heterogeneity of the disorder and its different aetiological aspects. A clinical dementia population and a control group were investigated with the following aims: I. To study the CSF levels of tau phosphorylated at threonine 181 (P-tau), total tau (T-tau) and ß-amyloid1-42 (Aß42) in the different diagnoses. II. To study associations between dementia disorder, cobalamin and/or folate deficiency, and gastritis. III. To study the presence and severity of CT brain changes in different dementia diagnoses. IV. To investigate to what extent different biomarkers and disease history contribute to the diagnostics of clinical dementia.I. CSF Levels of P-tau, T-tau and Aß42 were analysed with ELISA methods. Elevated CSF levels of P-tau were found in probable Alzheimer's disease (AD) patients compared with cognitively non-disturbed controls. Increased CSF T-tau, and decreased levels of Aß42 were found in both AD, mixed type of dementia, and vascular dementia (VaD) patients compared with the controls. Increased P-tau levels were more specific for AD pathology, but there was still an overlap with the controls, mixed dementia and VaD patients.II. Serological markers for cobalamin and folate deficiencies, and for gastritis were assessed in patients with different dementia diagnoses. Hyperhomocysteinaemia were commonly found in dementia without predominance in any of the investigated categories. Low levels of serum cobalamin or blood folate rarely reflected the elevated Hey levels. A lack of association between serological markers for cobalamin and folate deficiencies and for gastritis was demonstrated.III. A protocol for evaluation of the CT scans was used. Atrophy on the CT scans, although common in dementia, is an unspecific fmding in dementia of different backgrounds. White-matter changes and lacunes, indicating small-vessel disease, were common in dementia of different aetiologies. Dementia of mixed-type pathology was underestimated. More distinct criteria for this diagnostic category are warranted.IV. Partial Least Squares Discriminant Analysis (PLS-DA) was used on a large number of variables covering cognitive and biological markers and disease history. There were good discriminations of subgroups of dementia from the controls. However, the included variables were not able to distinguish between the investigated groups, indicating that several clinical parameters used in diagnosing dementia are in fact observed across different subtypes of dementia.It is concluded that there are no known biomarkers available that can provide a precise differential diagnosis of dementia. The clinical dementia diagnosis must still be based on a combination of a careful disease history, evaluation of risk factors, symptomatology, clinical findings, neurocognitive tests, blood analysis and other available methods such as CT and CSF markers.
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