| 1. |
- Behzadi, Arvin, 1994-
(författare)
-
Biomarkers for diagnosis and prognosis in amyotrophic lateral sclerosis
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of upper and lower motor neurons, leading to paresis, muscle atrophy, and respiratory failure. ALS can be difficult to diagnose and prognosticate early.Aim: To investigate the diagnostic and prognostic characteristics of biomarkers in cerebrospinal fluid (CSF), plasma, and skeletal muscle tissue in patients with ALS.Paper I: Neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) were analyzed in CSF using enzyme-linked immunosorbent assay (ELISA), and NFL in plasma was analyzed using single-molecule array (SIMOA). CSF NFL, CSF pNFH, and plasma NFL concentrations can differentiate ALS patients from ALS mimics, and were significantly negatively correlated with the disease duration in ALS patients.Paper II: Myosin heavy chain (MyHC) isoforms in extraocular muscles were investigated using immunofluorescence. Control donors had significantly higher proportion of myofibers containing MyHCIIa and significantly lower proportion of myofibers containing MyHCeom in the global layer compared to spinal-onset ALS and bulbar-onset ALS donors. Disease duration in the spinal-onset ALS donors was significantly correlated with the proportion of myofibers containing MyHCIIa in the global layer and MyHCeom in the orbital layer.Paper III: The study combined the neurofilament concentrations from Paper I, with cytokines previously analyzed in CSF and plasma using SIMOA, to investigate distinct molecular phenotypes in ALS. Patients with bulbar-onset ALS had significantly higher concentrations of CSF tumor necrosis factor α (TNF-α) compared to ALS mimics. TNF-α and NFL were significantly correlated with each other in both CSF and plasma in ALS patients. Combined analysis of NFL and IL-6 in plasma identified molecular prognostic subgroups in ALS patients.Paper IV: Creatine kinase (CK), high-sensitivity cardiac troponin T (hs-cTnT), hs-cTnI, and cystatin C (CysC) were analyzed in plasma in a fully accredited laboratory. CK and hs-cTnT concentrations were significantly elevated in limb-onset ALS compared to controls and bulbar-onset ALS. hs-cTnT concentrations were significantly elevated in truncal-onset ALS compared to controls and bulbar-onset ALS. Multivariable Cox proportional hazards models indicated elevated concentrations of CysC as a significant marker for worse prognosis in ALS.Conclusions: The papers report diagnostic and prognostic characteristics of biomarkers in CSF, plasma, and muscle tissue in ALS patients. The significant findings for biomarkers in plasma could be of value since plasma sampling does not involve a lumbar puncture.
|
|
| 2. |
- Forsberg, Anton
(författare)
-
Amyloid imaging in Alzheimer’s disease and mild cognitive impairment by positron emission tomography
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Effectiveness of future treatment strategies in Alzheimer s disease (AD) will rely on early detection of disease and the possibility to clearly evaluate their effects. The findings presented in this thesis concerns both early in vivo detection of amyloid deposition in the brains of patients at risk of developing AD and the longitudinal changes of pathological and functional parameters in patients with AD. A couple of years ago the first study with in vivo detection of amyloid using the radiotracer N-methyl [11C] 2-(4´-methylaminophenyl)-6-hydroxy-benzothiazole also known as 11C-Pittsburgh Compound B (11C-PIB) with positron emission tomography (PET) was performed in collaboration between researchers in Pittsburgh, USA, Uppsala and Stockholm, Sweden. This first study showed a significant difference between AD patients and healthy controls in regards to their 11C-PIB retention. The research presented in this thesis is both continuations and new investigations based on this initial research. Results obtained in the studies presented in this thesis showed that the amyloid deposition is an early event in the development of AD present already in patients with mild cognitive impairment (MCI) that later develop AD. We could also show that the amyloid deposition in brain was closely correlated to concentrations of pathological biomarkers in the cerebrospinal fluid (CSF) at an early stage. While functional decline with decreased cerebral metabolic rate of glucose (CMRglc) measured with 18F-FDG PET and episodic memory tests did not show a relationship in MCI patients but did at the clinical stage of AD. Our results also suggests that the early deposition of amyloid increase to a certain level and then reaches a plateau as shown by a quite stable 11C-PIB retention in AD patients followed for a mean period of 2.5 years. We could also show that the dynamic 11C-PIB PET scan do not only contain information on amyloid load but also information on brain function as the early frames contain a blood flow component that is related to CMRglc. The general conclusions to be drawn from these studies are that 11C-PIB PET shows promising results of both early detection of disease and the possibility to use it for evaluation of current and future anti-amyloid therapies. The possibility to extract functional information will further increase the usefulness of 11C-PIB PET in AD research and clinical assessment of dementia.
|
|
| 3. |
- Forsberg, Karl Anton, 1955-
(författare)
-
Att främja förändrad livsstil bland personer med psykiskt funktionshinder : studier av metabola och psykologiska effekter, upplevd mening och hälsa
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis is to investigate if the somatic comorbidity and increased mortality among persons with psychiatric disability (residents in supported housing facilities) can be influenced. The thesis comprises four papers. Paper I describes the lived experience of health and body. Papers II and III examine the effects of a lifestyle programme on physiological markers (II) and on psychological and quality of life parameters (III). Paper (IV) illustrates the meaning of participating in a life style programme. The data in Papers I and IV comprises narrative interviews with residents (n=11). The studies in Papers II and III are focused on residents and were carried out with a randomized design. The randomization was performed on a group level (supported housing facility). The 12 month intervention consisted of study circles with a theoretical and practical application of dietary information and physical activity for two hours, on a twice weekly basis under the supervision of a study circle leader. The controls were offered an aesthetic study circle and met once a week. The data in Paper II comprises physiological quantitative data from both residents (n=41) and staff (n=41) and in Paper III questionnaires on symptoms and quality of life completed only by residents (n=41). The data was analysed with Qualitative description (I), Phenomenological-hermeneutics (IV), and for papers II and III relevant statistical calculations were used. Health is described in paper I as “having a life as others have” and discloses the losses of important life domains (family, work, security) and the experiences of being deviant and stigmatized. Health is described as “absence of psychological and physical problems” and its hampering effects on quality of life and self-esteem. Health is understood as a phenomenon that could “be influenced by one self”, and there is an insight that health is manageable. Participating in a life style intervention (paper II) meant a significant improvement in risk factors for metabolic syndrome among the residents in comparison with controls. No differences were seen on weight, BMI and improved physical capacity. In paper III a significant positive increase in the Sense of Coherence compared to controls was seen. However no effect was seen on quality of life, psychosocial function or on reduction of symptoms in comparison with controls. Participating in a lifestyle intervention can be understood as the gaining of insights that health can be improved and that the daily life is partly given a changed content (paper II). The participation is also described as meaning an increased sense of closeness and equality in relation to the staff and sometimes a painful insight of their life situation. Participating is also described as entailing a hope that one’s life situation can be affected. In summary this thesis shows that there is some possibility of influencing the physical health (reduced risk of metabolic syndrome) among persons with psychiatric disability by participating in a 12 month intervention programme. The intervention does not show any effects on measures such as quality of life, psychosocial function and presence of symptoms. However, the participants describe that the participation had a meaning in a number of respects. This is a finding that is confirmed by the positive change in sense of coherence. The need to develop preventive care for persons with psychiatric disability and the importance of monitoring the treatment with neuroleptics and its side effects on physical health is an important clinical implication. Furthermore the importance of the responsibility of the care staff is emphasized as well as the importance of supporting a change in lifestyle.
|
|
