| 1. |
- Engler, Henry, et al.
(author)
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Two-year follow-up of amyloid deposition in patients with Alzheimer's disease
- 2006
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 129:Pt 11, s. 2856-2866
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Journal article (peer-reviewed)abstract
- Beta amyloid is one of the major histopathological hallmarks of Alzheimer's disease. We recently reported in vivo imaging of amyloid in 16 Alzheimer patients, using the PET ligand N-methyl[11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole (PIB). In the present study we rescanned these 16 Alzheimer patients after 2.0 +/- 0.5 years and have described the interval change in amyloid deposition and regional cerebral metabolic rate for glucose (rCMRGlc) at follow-up. Sixteen patients with Alzheimer's disease were re-examined by means of PET, using PIB and 2-[18F]fluoro-2-deoxy-d-glucose (FDG) after 2.0 +/- 0.5 years. The patients were all on cholinesterase inhibitor treatment and five also on treatment with the N-methyl-d-aspartate (NMDA) antagonist memantine. In order to estimate the accuracy of the PET PIB measurements, four additional Alzheimer patients underwent repeated examinations with PIB within 20 days (test-retest). Relative PIB retention in cortical regions differed by 3-7% in the test-retest study. No significant difference in PIB retention was observed between baseline and follow-up while a significant (P < 0.01) 20% decrease in rCMRGlc was observed in cortical brain regions. A significant negative correlation between rCMRGlc and PIB retention was observed in the parietal cortex in the Alzheimer patients at follow-up (r = 0.67, P = 0.009). A non-significant decline in Mini-Mental State Examination (MMSE) score from 24.3 +/- 3.7 (mean +/- standard deviation) to 22.7 +/- 6.1 was measured at follow-up. Five of the Alzheimer patients showed a significant decline in MMSE score of >3 (21.4 +/- 3.5 to 15.6 +/- 3.9, P < 0.01) (AD-progressive) while the rest of the patients were cognitively more stable (MMSE score = 25.6 +/- 3.1 to 25.9 +/- 3.7) (AD-stable) compared with baseline. A positive correlation (P = 0.001) was observed in the parietal cortex between Rey Auditory Verbal Learning (RAVL) test score and rCMRGlc at follow-up while a negative correlation (P = 0.018) was observed between RAVL test and PIB retention in the parietal at follow-up. Relatively stable PIB retention after 2 years of follow-up in patients with mild Alzheimer's disease suggests that amyloid deposition in the brain reaches a plateau by the early clinical stages of Alzheimer's disease and therefore may precede a decline in rCMRGlc and cognition. It appears that anti-amyloid therapies will need to induce a significant decrease in amyloid load in order for PIB PET images to detect a drug effect in Alzheimer patients. FDG imaging may be able to detect a stabilization of cerebral metabolism caused by therapy administered to patients with a clinical diagnosis of Alzheimer's disease.
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| 2. |
- Forsberg, Anton
(author)
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Amyloid imaging in Alzheimer’s disease and mild cognitive impairment by positron emission tomography
- 2008
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Doctoral thesis (other academic/artistic)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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| 3. |
- Forsberg, Anton, et al.
(author)
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PET imaging of amyloid deposition in patients with mild cognitive impairment
- 2008
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1456-1465
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Journal article (peer-reviewed)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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| 4. |
- Forsberg, Karl Anton, 1955-
(author)
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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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Doctoral thesis (other academic/artistic)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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| 5. |
- Forsberg, Karl Anton, et al.
(author)
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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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In: Nordic Journal of Psychiatry. - : Informa UK Limited. - 1502-4725 .- 0803-9488. ; 62:6, s. 486-495
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Journal article (peer-reviewed)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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| 6. |
- Kadir, Ahmadul, et al.
(author)
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Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease.
- 2008
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In: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 63:5, s. 621-31
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The effects of (-)-phenserine (phenserine) and placebo/donepezil treatment on regional cerebral metabolic rate for glucose (rCMRglc) and brain amyloid load were investigated by positron emission tomography in 20 patients with mild Alzheimer's disease in relation to cerebrospinal fluid (CSF) and plasma biomarkers, and cognitive function. METHODS: The first 3 months of the study was a randomized, double-blind, placebo-controlled phase, during which 10 patients received phenserine (30 mg/day) and 10 patients the placebo. Three to 6 months was an open-label extension phase, during which the placebo group received donepezil (5 mg/day) and the phenserine group remained on phenserine. After 6 months, all patients received phenserine treatment up to 12 months. The patients underwent positron emission tomography examinations to measure rCMRglc (8F-FDG) and amyloid load (11C-PIB) at baseline and after 3 and 6 months of the treatment. Neuropsychological and biomarker data were collected at the three times of positron emission tomography imaging. RESULTS: Statistically significant effects on a composite neuropsychological test score were observed in the phenserine-treated group compared with the placebo and donepezil group at 3 and 6 months, respectively. Values of rCMRglc were significantly increased in several cortical regions after 3 months of phenserine treatment, compared with baseline, and correlated positively with cognitive function and CSF beta-amyloid 40 (Abeta40). Cortical Pittsburgh Compound B retention correlated negatively with CSF Abeta40 levels and the ratio Abeta/beta-secretase-cleaved amyloid precursor protein. In CSF, Abeta40 correlated positively with the attention domain of cognition. INTERPRETATION: Phenserine treatment was associated with an improvement in cognition and an increase in rCMRglc.
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