PET and MR imaging in Parkinson’s disease patients with cognitive impairment. A study of dopaminergic dysfunction, amyloid deposition, cortical hypometabolism and brain atrophy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by a severe loss of substantia nigra dopaminergic neurons leading to dopamine depletion in the striatum. PD affects movement, producing motor symptoms such as rigidity, tremor and bradykinesia. Non-motor symptoms include autonomic dysfunction, neurobehavioral problems and cognitive impairment, which may lead to dementia. The pathophysiological basis of cognitive impairment and dementia in PD is unclear. The aim of this thesis was to study the pathophysiological basis of cognitive impairment and dementia in PD. We evaluated the relation between frontostriatal dopaminergic dysfunction and the cognitive symptoms in PD patients with [18F]Fdopa PET. We also combined [C]PIB and [¹⁸F]FDG PET and magnetic resonance imaging in PD patients with and without dementia. In addition, we analysed subregional striatal [¹⁸F]Fdopa PET data to find out whether a simple ratio approach would reliably separate PD patients from healthy controls. The impaired dopaminergic function of the frontostriatal regions was related to the impairment in cognitive functions, such as memory and cognitive processing in PD patients. PD patients with dementia showed an impaired glucose metabolism but not amyloid deposition in the cortical brain regions, and the hypometabolism was associated with the degree of cognitive impairment. PD patients had atrophy, both in the prefrontal cortex and in the hippocampus, and the hippocampal atrophy was related to impaired memory. A single 15-min scan 75 min after a tracer injection seemed to be sufficient for separating patients with PD from healthy controls in a clinical research environment. In conclusion, the occurrence of cognitive impairment and dementia in PD seems to be multifactorial and relates to changes, such as reduced dopaminergic activity, hypometabolism, brain atrophy and rarely to amyloid accumulation.

Kjærlighet i forbundethet : en kraft i gamle menneskers åndelighet og verdighet

The thesis is rooted in caring science and the notion that the human being is an indivisible unity of body, soul and spirit. The purpose is to search for new, or expanded knowledge and understanding of the substance of the human’s spiritual space, as well as aspects that may constitute a foundation for the safeguard of human dignity. The clinical research study concerns the importance of spirituality and dignity in the care for older people. The thesis consists of three substudies with four articles, and the methodology is based on Gadamer’s philosophical hermeneutics. Through a metasynthesis of 17 research articles, sub-study I searched for understanding of the concept of spirituality as it may appear in reality (deduction). 17 older people were interviewed in sub-study II. This sub-study sought understanding for spirituality and dignity in the specific reality (induction). Sub-study III searched for theory development regarding spirituality, through a literature review of 20 research articles and a text by Tillich (abduction). The findings imply that spirituality entails human beings’ connectedness with one’s inner space and connectedness beyond oneself. Love in connectedness appears as a force in both spirituality and dignity. Themes portrayed include understanding of the spiritual space, religiousness, dignity, and spiritual care. The relationship between dignity and spirituality can be seen in the confirmation of human worth and care for the whole human being, including the spiritual dimension, and this is understood as a prerequisite for perceived dignity. It seems to be important that older people feel valued, loved, not abandoned, and alive. The theoretical model portrays love as a reunifying and connecting force that may foster confirmation, serving, longing and holiness. The movement towards connectedness may create room for the human being’s perception of dignity and holiness, and as such, it may be a force in the search for wholeness and becoming in health.

Enhancing the Availability of Electronic Health Records for Secondary Purposes – A Case Study

Due to the sensitive nature of patient data, the secondary use of electronic health records (EHR) is restricted in scientific research and product development. Such restrictions pursue to preserve the privacy of respective patients by limiting the availability and variety of sensitive patient data. Current limitations do not correspond with the actual needs requested by the potential secondary users. In this thesis, the secondary use of Finnish and Swedish EHR data is explored for the purpose of enhancing the availability of such data for clinical research and product development. Involved EHR-related procedures and technologies are analysed to identify the issues limiting the secondary use of patient data. Successful secondary use of patient data increases the data value. To explore the identified circumstances, a case study of potential secondary users and use intentions regarding EHR data was carried out in Finland and Sweden. The data collection for the conducted case study was performed using semi-structured interviews. In total, 14 Finnish and Swedish experts representing scientific research, health management, and business were interviewed. The motivation for the corresponding interviews was to evaluate the protection of EHR data used for secondary purposes. The efficiency of implemented procedures and technologies was analysed in terms of data availability and privacy preserving. The results of the conducted case study show that the factors affecting EHR availability are divided to three categories: management of patient data, preservation of patients' privacy, and potential secondary users. Identified issues regarding data management included laborious and inconsistent data request procedures and the role and effect of external service providers. Based on the study findings, two secondary use approaches enabling the secondary use of EHR data are identified: data alteration and protected processing environment. Data alteration increases the availability of relevant EHR data, further decreasing the value of such data. Protected processing approach restricts the amount of potential users and use intentions while providing more valuable data content.

Clinical Learning Environment and Supervision. Development and Validation of the CLES Evaluation Scale

The purpose of the study is: (1) to describe how nursing students' experienced their clinical learning environment and the supervision given by staff nurses working in hospital settings; and (2) to develop and test an evaluation scale of Clinical Learning Environment and Supervision (CLES). The study has been carried out in different phases. The pilot study (n=163) explored the association between the characteristics of a ward and its evaluation as a learning environment by students. The second version of research instrument (which was developed by the results of this pilot study) were tested by an expert panel (n=9 nurse teachers) and test-retest group formed by student nurses (n=38). After this evaluative phase, the CLES was formed as the basic research instrument for this study and it was tested with the Finnish main sample (n=416). In this phase, a concurrent validity instrument (Dunn & Burnett 1995) was used to confirm the validation process of CLES. The international comparative study was made by comparing the Finnish main sample with a British sample (n=142). The international comparative study was necessary for two reasons. In the instrument developing process, there is a need to test the new instrument in some other nursing culture. Other reason for comparative international study is the reflecting the impact of open employment markets in the European Union (EU) on the need to evaluate and to integrate EU health care educational systems. The results showed that the individualised supervision system is the most used supervision model and the supervisory relationship with personal mentor is the most meaningful single element of supervision evaluated by nursing students. The ward atmosphere and the management style of ward manager are the most important environmental factors of the clinical ward. The study integrates two theoretical elements - learning environment and supervision - in developing a preliminary theoretical model. The comparative international study showed that, Finnish students were more satisfied and evaluated their clinical placements and supervision with higher scores than students in the United Kingdom (UK). The difference between groups was statistical highly significant (p= 0.000). In the UK, clinical placements were longer but students met their nurse teachers less frequently than students in Finland. Arrangements for supervision were similar. This research process has produced the evaluation scale (CLES), which can be used in research and quality assessments of clinical learning environment and supervision in Finland and in the UK. CLES consists of 27 items and it is sub-divided into five sub-dimensions. Cronbach's alpha coefficient varied from high 0.94 to marginal 0.73. CLES is a compact evaluation scale and user-friendliness makes it suitable for continuing evaluation.