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- Bäckström, David C, M.D. 1978-
(författare)
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The biology of cognitive decline and reduced survival in Parkinson disease : prognostic factors in a population-based cohort
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson disease (PD) is a progressive neurodegenerative disease that affects about 1% of the population over 60 years. The cardinal symptoms are motor disabilities but cognitive decline is also common. About 50% of all persons with PD develop dementia within 10 years after disease onset. Dementia in PD account for high social costs and has large, negative effects on quality of life. Aims. The aim of the study was to investigate clinical, neurobiological and genetic factors of importance for progression and for the prognosis in PD and parkinsonism. First, we aimed to describe mortality and risk factors for death, including possible associations with cognitive dysfunction, in patients with idiopathic parkinsonism. Second, we aimed to study if biomarkers in the cerebrospinal fluid (CSF) are useful for the diagnosis of different forms of idiopathic parkinsonism and prediction of cognitive decline in PD. Methods. A population-based cohort consisting of patients with new-onset, idiopathic parkinsonism was studied prospectively. After screening in a catchment area of ~142 000 inhabitants in Sweden, 182 patients with parkinsonism were included. The patients were investigated comprehensively, including neuropsychological testing, multimodal neuroimaging and genetic and biosample analyses. During follow up, 143 patients were diagnosed with PD, 13 with multiple system atrophy (MSA), and 18 with progressive supranuclear palsy (PSP). A total of 109 patients died. Results. Patients with MSA and PSP had the shortest life expectancy. PD patients who presented with normal cognitive function had a largely normal life expectancy. In contrast, the mortality was increased in PD patients with cognitive impairment, freezing of gait, hyposmia, and mildly elevated leukocytes in the CSF. Of importance for the prognosis, patients with PD with an early CSF pattern of high Neurofilament light protein, low β-amyloid, and high heart fatty acid binding protein had an 11.8 times increased risk of developing PD dementia (95% CI 3.3-42.1, p <0.001), compared with PD patients with a more ”normal” CSF pattern. Variation in genes associated with dopamine function was also associated with some effects on cognitive functions in PD. Conclusions. PD subtypes, for instance the subtype characterized by cognitive decline, have distinguishing clinical, neurochemical and neurobiological traits, which are of importance for the prognosis and the survival. An early CSF analysis is useful for predicting cognitive decline. The finding of a low-grade immune reaction in the CSF of patients with PD may have clinical implications. In clinical practice, CSF biomarkers could be useful for improving diagnosis and prognostication.
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| 2. |
- Sperens, Maria, 1958-
(författare)
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Att leva med Parkinsons sjukdom : med fokus på konsekvenser i dagligt liv för kvinnor och män
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson’s disease (PD) is a common, progressive neurodegenerative disorder. It is characterized by motor symptoms, such as stiff muscles, slowness of movements, tremor, gait and balance difficulties, and also by non-motor symptoms such as depression, sleeping disorders, fatigue, sexual dysfunction, cognitive decline and pain. In an advanced stage of the disease, dementia can be developed. The disease occurs in all ethnic groups and affects both women and men. In 2016, the world wide prevalence of PD was estimated to 6.1 million people (2.9 million women, 3.1 men). In Sweden there are currently about 20 000 persons diagnosed with PD. There is no cure for PD. The main goal of treatment is for the patient to achieve best possible quality of life. The basic treatment for PD is oral medication, but for some, with a more advanced disease, alternative ways to distribute medicine, and/or neurosurgery (deep brain stimulation, DBS) may be an alternative. Today, there is an increasing awareness of the need of medical research, based on sex/gender. Among those living with PD, more men than women undergo highly specialised treatment with neurosurgery, even though women after surgery experienced greater benefit in ADL, in emotions and in social life. In a progressive disease as PD, changes in ADL can appear both suddenly and gradually. Earlier studies have shown that PD affects ADL already in an early stage of the disease, and also that maintenance of activities is important for well-being in daily life.The overall aim of this thesis was to gain knowledge of daily life among women and men with Parkinson’s disease and to explore how they relate to and manage aspects of consequences of the disease. The specific aims were to investigate how persons with moderately advanced Parkinson’s disease manage consequences of the disease in their daily life, how they reason about DBS as a treatment alternative, to evaluate the development of ADL over time in persons living with PD, from the time of diagnosis up to eight years, and finally, to explore similarities and differences among women and men.Method: Qualitative interviews were conducted with 24 persons with PD (PwPD), 14 men and 10 women. The interviews were analysed according to Grounded Theory (GT). Comparisons between patterns in men and women were made. The quantitative study included 129 PwPD from the NYPUM project (Ny Parkinsonism in UMeå). Data from baseline assessment, and then from follow-ups at one, three, five and eight years have been used. Participants estimated their ability to perform daily activities based on the ADL-taxonomy. Data have been analysed statistically with respect to development over time, as well as differences between men and women. Linear Mixed Model was chosen for analyses.Results: To achieve the best possible everyday life, in spite of the difficulties PD caused, it was important for the participants to adapt to their medication regime and also to ongoing changes in their abilities. The interviewees tried to think in a positive way, prioritize among social relations and activities, to take advantage of positive environments and to exercise physically. Participants had a good knowledge of DBS as an alternative treatment method although it was not their choice at the actual time point. They worried about the neurosurgical procedure and were hesitant about the outcome of DBS. The treatment was seen as a step-way process, and DBS was seen as the last option. In the quantitative study, nine out of 12 activity domains showed a statistically significant change over time. Seven of these were basic, needed to be performed almost every day. The two remaining ADL-domains (Shopping and Cleaning) also showed a statistically significant difference between women and men, showing that women experienced a higher degree of detoriation. Those 32 remaining at eight years, still fulfilling the ADL-taxonomy, did not seem to experience that PD had a big impact on their ADL-ability. Overall, in these studies, there were more similarities than differences between women and men.Discussion: Our results support the importance of PwPD maintain routines regarding food, medicine and daily activities, adapt their way to perform tasks, and engage in meaningful and values activities as a way to achieve a good, daily life. Occupational therapists with good knowledge in PD could contribute in facilitating to use this strategies. Concerning DBS, the participants had comparatively low expectations on the outcome. This might be explained by a high level of education and a high percentage being member in a PD-society. Of the nine ADL domains showing change over time, seven were likely to be needed to be performed every day (e.g. Mobility and Dressing). The two remaining, (Shopping and Cleaning) are activities that are challenging for PwPD. They are also such activities where it is generally known that there are differences between women and men.Conclusion: Various aspects of activity appear to be important factors in the assessment, treatment and follow-up of PwPD. Meaningful activities, adapting the way of performing various tasks, as well as a functioning schedule based on food, medicines and activity are important elements in the strive for a good daily life. Deep brain stimulation (DBS) seems to be considered as the last step in a step-by-step approach to treatment options. Those who still perform self-assessment according to the ADL taxonomy at eight years follow-up, do not seem to experience that PD have a major impact on their perceived ability. The results also implies that men and women have a similar development over time regarding ADL ability and that they reason in a similar way with regard to strategies for achieving good daily life and about deep DBS as a treatment option.
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| 3. |
- Wagner, Ryan G, 1984-
(författare)
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The Burden of Epilepsy : using population-based data to define the burden and model a cost-effective intervention for the treatment of epilepsy in rural South Africa
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rationale Epilepsy is a common, chronic, neurological condition that disproportionately affects individuals living in low- and middle- income countries, including much of sub-Saharan Africa. Epilepsy is treatable, with the majority of individuals who take anti-epileptic drugs experiencing a reduction, or elimination, of seizures. Yet the number of individuals taking and adhering to medication in Africa is low and interventions aimed at improving treatment are lacking.Aims To define the epidemiology of convulsive epilepsy in rural South Africa in terms of incidence, mortality and disability-adjusted life years; to determine outpatient, out-of-pocket costs resulting from epilepsy treatment; to establish the level of adherence to anti-epileptic drugs amongst people with epilepsy; and, to determine whether the introduction of routine visits to people with epilepsy by community health workers is a cost-effective intervention for improving adherence to anti-epileptic drugs.Methods Nested within the Agincourt Health and Demographic Surveillance System, this work utilized a cohort of individuals diagnosed with convulsive epilepsy in 2008 to determine health care utilization and out-of-pocket costs due to care sought for epilepsy. Additionally, using blood samples from the cohort, anti-epileptic drug adherence was measured and, following the cohort, mortality rates were determined. Using these collected epidemiological parameters, disability-adjusted life years due to convulsive epilepsy were determined. Finally, combining the epidemiological and cost parameters, a community health worker intervention was modeled to determine its incremental cost-effectiveness ratio.Key Findings The burden of convulsive epilepsy is lower in rural South Africa than other parts of Africa, likely due to lower levels of known risk factors. Yet the burden, especially in terms of mortality, remains high, as does the treatment gap and health care utilization. Findings from the economic evaluation found the introduction of a community health worker to be highly cost-effective and would likely lower the burden of epilepsy in rural South Africa.Implications Epilepsy contributes to the burden of disease in rural South Africa, with high levels of mortality and a substantial treatment gap. The introduction of a community-health worker is likely to be one cost-effective, community based intervention that would lower the burden of epilepsy by improving adherence to anti-epileptic drugs. Implementing this intervention, based on these findings, is a justified and important next step.
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