| 11. |
- Forsberg, Anton
(författare)
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Amyloid imaging in Alzheimer’s disease and mild cognitive impairment by positron emission tomography
- 2008
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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.
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| 12. |
- Forsberg, Anton, et al.
(författare)
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Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer's disease patients
- 2013
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer-Verlag New York. - 1619-7070 .- 1619-7089. ; 40:4, s. 580-593
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD).METHODS: In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [(11)C]AZD2995 and [(11)C]AZD2184 in three healthy control subjects and seven AD patients.RESULTS: AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [(3)H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [(11)C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [(11)C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus.CONCLUSION: Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [(11)C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [(11)C]AZD2995. However, the very low nonspecific binding of [(11)C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy.
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| 13. |
- Forsberg, Anton, et al.
(författare)
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PET imaging of amyloid deposition in patients with mild cognitive impairment
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1456-1465
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Tidskriftsartikel (refereegranskat)abstract
- It is of great clinical value to identify subjects at a high risk of developing AD. We previously found that the amyloid positron emission tomography (PET) tracer PIB showed a robust difference in retention in the brain between AD patients and healthy controls (HC). Twenty-one patients diagnosed with MCI (mean age 63.3 ± 7.8 (S.D.) years) underwent PET studies with 11C-PIB, and 18F-fluoro-deoxy-glucose (FDG) to measure cerebral glucose metabolism, as well as assessment of cognitive function and CSF sampling. Reference group data from 27 AD patients and 6 healthy controls, respectively, were used for comparison. The mean cortical PIB retention for the MCI patients was intermediate compared to HC and AD. Seven MCI patients that later at clinical follow-up converted to AD (8.1 ± 6.0 (S.D.) months) showed significant higher PIB retention compared to non-converting MCI patients and HC, respectively (ps < 0.01). The PIB retention in MCI converters was comparable to AD patients (p > 0.01). Correlations were observed in the MCI patients between PIB retention and CSF Aβ1-42, total Tau and episodic memory, respectively.
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| 14. |
- Forsberg, Anton, et al.
(författare)
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The use of PIB-PET as a dual pathological and functional biomarker in AD
- 2012
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Ingår i: Biochimica et Biophysica Acta - Molecular Basis of Disease. - : Elsevier BV. - 0925-4439 .- 1879-260X. ; 1822:3, s. 380-385
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid imaging with positron emission tomography (PET) is presently used in Alzheimer's disease (AD) research. In this study we investigated the possibility to use early frames (ePIB) of the PIB scans as a rough index of CBF by comparing normalised early PIB values with cerebral glucose metabolism (rCMRglc). PIB-PET and FDG-PET were performed in 37 AD patients, 21 subjects with mild cognitive impairment (MCI) and 6 healthy controls (HC). The patients were divided based on their PIB retention (amyloid load) as either PIB positive (PIB+) or PIB negative (PIB-). Data of the unidirectional influx K-1 from a subset of the subjects including 7 AD patients and 3 HC was used for correlative analysis. Data was analysed using regions of interest (ROI) analysis. A strong, positive correlation was observed across brain regions between K-1 and ePIB (r=0.70: p <= 0.001). The ePIB values were significantly lower in the posterior cingulate (p <= 0.001) and the parietal cortices (p = 0.002) in PIB+ subjects compared to PIB-, although the group difference were stronger for rCMRglc in cortical areas (p <= 0.001). Strong positive correlations between ePIB and rCMRglc were observed in all cortical regions analysed, especially in the posterior cingulate and parietal cortices (p <= 0.001). A single dynamic PIE-PET scan may provide information about pathological and functional changes (amyloidosis and impaired blood flow). This might be important for diagnosis of AD, enrichment of patients in clinical trials and evaluation of treatment effects.
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| 15. |
- Forsberg, Karl Anton, 1955-
(författare)
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Att främja förändrad livsstil bland personer med psykiskt funktionshinder : studier av metabola och psykologiska effekter, upplevd mening och hälsa
- 2009
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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.
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| 16. |
- Forsberg, Karl Anton, 1955-, et al.
(författare)
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Experiences of health among persons with psychiatric disabilityparticipating in a life style intervention
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Persons with psychiatric disabilities describe health in similar ways to others, although the prevalence of ill-health and risk factors are larger than in the general population. Aim: To describe the experience of health and body in order to enable the creation of health interventions for this group of users. Design: The first author interviewed five women and six men with psychiatric disabilities, aged 26 to 53, participating in a life style programme. Method: The transcribed interviews were analysed by qualitative description. Result: The categories “Health is having a life as others have” disclosed losses of important life domains and experiences of being different, and “Health is absence of psychological and physical problems” describes their symptoms and its hampering effects on quality of life and self-esteem. The category “Health is being able to influence one’s own health” reveals a sense of hope that health is manageable. Conclusion: Not having a life or being as others causes a sense of being different and stigmatization, which might affect self esteem, quality of life and possibilities for recovery. Health is to be spared physical and psychological problems as the lack of energy which affects motivation and the ability to gain a quality of life. But health is also described in terms of a conviction that it can be affected through knowledge and self-management of symptoms. Clinical implications: Health intervention programmes should be designed in such a way that promotes motivation and self-management as it is an important factor in recovery. Carers should also promote and support clients to find activities, relationships and sites where symptom relief can be experienced.
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| 17. |
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| 18. |
- Forsberg, Karl Anton, 1955-, et al.
(författare)
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Influence of a life style intervention among persons with a psychiatric disability : a cluster randomised controlled trial on symptoms, quality of life and sense of coherence
- 2010
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Ingår i: Journal of Clinical Nursing. - Malden : Wiley-Blackwell. - 0962-1067 .- 1365-2702. ; 19:11-12, s. 1519-1528
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Tidskriftsartikel (refereegranskat)abstract
- Aims and objectives: The aim of this study was to investigate how a life style intervention programme influences psychiatric and psychosocial factors among persons with psychiatric disabilities. Background: Persons with psychiatric disabilities often suffer from a simultaneous physical health problem, where circulatory disorder, hyperlipideamia, digestive disease, diabetes mellitus and obesity are prevalent. Studies have also shown a relationship between physical activity and mental health. But few randomised controlled trails have been aimed specifically at life style interventions and their effect on psychiatric health and quality of life among persons with psychiatric disabilities.Design: a cluster randomised controlled trail.Methods: Forty one persons with a DSM- ІV diagnosis in eight supported housing facilities and two housing support programmes and their carers were on cluster level randomly assigned to a 12 month health intervention programme in the form of study circles with diet sessions and physical activities or a control programme. The changes in the mean of quality of life, level of functioning, psychiatric symptoms and sense of coherence was investigated and its relationship to physical health and attendance.Results: A significant increase in the sense of coherence was seen in both programmes but also significant improvements in the intervention group compared to controls at the follow-up.Conclusions: Structured activities in the form of life style intervention programmes with a sufficient level of challenge that encourage persons with psychiatric disabilities to participate in activities in a social context may contribute to a significant increase in the sense of coherence.Relevance to clinical practice: Improving physical health with life style programmes in the form of study circles and when involving their cares will in addition to increased physical health end in improved sense of coherence.
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| 19. |
- Forsberg, Karl-Anton, et al.
(författare)
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Meanings of participating in a lifestyle programme for persons with psychiatric disabilities.
- 2011
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 25:2, s. 357-364
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Tidskriftsartikel (refereegranskat)abstract
- Lifestyle changes that affect physical and psychological health are described in research literature; however, the meaning of participating in a lifestyle intervention programme together with the staff has not been described. This study illuminates meanings of participating in a lifestyle programme as experienced by persons with psychiatric disabilities. The first author interviewed five women and six men with schizophrenia and depressive syndrome, aged 26-53, participating in a lifestyle programme. The transcribed interviews were analysed using a phenomenological hermeneutic approach inspired by the philosophy of Ricoeur. Meanings of participating in a lifestyle programme include my health can be improved as both the physical effects and the obstacles are considered and the daily life is partially given a changed content in new experiences and by participating in something to take pride in. The meanings of participating together with the staff mean an increased sense of closeness and equality with the staff expressed in changes in relationships and the difference between the two groups being revealed and also in becoming aware of the life situation, an insight into the loss of a healthy life but also hope for the future is expressed. The conclusions that could be drawn from this study are that a lifestyle intervention affects health and other important life areas such as the content of daily life and the relationship with the carers, which appears to affect the sense of hope and the ability to see new possibilities. Carers should find situations and activities where the residents and carers participate under equal conditions giving the residents the opportunity to leave the sick roll, experience equality and develop good relationships.
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| 20. |
- Forsberg, Karl Anton, et al.
(författare)
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Physical health a cluster randomized controlled lifestyle intervention among persons with a psychiatric disability and their staff
- 2008
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 1502-4725 .- 0803-9488. ; 62:6, s. 486-495
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to explore the impact on physical health of a lifestyle programme among persons with psychiatric disabilities, and their caregivers. Their satisfaction with the intervention was also assessed. Somatic comorbidity and an increased mortality related to the lifestyle among persons with psychiatric disabilities are well known. Few randomized controlled trials have been aimed specifically at lifestyle issues among persons with a psychiatric disability. This trial includes clients with psychiatric disabilities living in supported housing and their staff. Forty-one persons with a DSM-?V diagnosis of severe mental illness from psychiatric disability from 10 supported housing facilities and 41 of their caregivers participated in this 12-month study during 2005-2006 in Sweden. The supported housing facilities with residents and staff were randomly assigned to either a health intervention programme or a control programme with an aesthetic content. The presence of metabolic syndrome and changes in the mean of physiological parameters such as Hba1c, P-glucose, P-insulin, lipids, blood pressure, physical working capacity, body mass index, Heart Score were investigated and participants' satisfaction assessed. There was a significant reduction in the mean of metabolic syndrome criteria in the intervention group compared with the control group at the follow-up. The participants expressed satisfaction with the programme. The results indicate that health interventions on lifestyle issues when involving carers are appreciated, feasible and could be successful in reducing some health-related risk factors among persons with psychiatric disabilities.
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