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- Kadir, Ahmadul, et al.
(författare)
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PET imaging of the in vivo brain acetylcholinesterase activity and nicotine binding in galantamine-treated patients with AD
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:8, s. 1204-1217
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Tidskriftsartikel (refereegranskat)abstract
- The effect of galantamine treatment on cortical acetylcholinesterase (AChE) activity and nicotinic receptor binding was investigated by positron emission tomography (PET) in 18 patients with mild Alzheimer's disease (AD) in relation to galantamine concentration and the patients’ cognitive performances. The first 3 months of the study was of a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16–24 mg/day) and 6 patients the placebo, and this was followed by 9 months’ galantamine treatment in all patients. The patients underwent PET examinations to measure cortical AChE activity (11C-PMP) and 11C-nicotine binding. Neuropsychological tests were performed throughout the study. Inhibition (30–40%) of cortical AChE activity was observed after 3 weeks to 12 months of galantamine treatment. No significant change in mean cortical 11C-nicotine binding was observed during the study. 11C-Nicotine binding, however, positively correlated with plasma galantamine concentration. Both the changes of AChE activity and 11C-nicotine binding correlated positively with the results of a cognitive test of attention. In conclusion, galantamine caused sustained AChE inhibition for up to 12 months. At the individual level, the in vivo cortical AChE inhibition and 11C-nicotine binding were associated with changes in the attention domain of cognition rather than episodic memory.
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- Darreh-Shori, T., et al.
(författare)
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Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in AD patients treated with galantamine
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:2, s. 168-184
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between acetylcholinesterase (AChE) activity in the CSF and brain of patients with Alzheimer's disease (AD) was investigated in 18 mild AD patients following galantamine treatment. The first 3 months of the study had a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16-24 mg/day) and six patients placebo. This was followed by 9 months Galantamine treatment in all patients. Activities and protein levels of both the "read-through" AChE (AChE-R) and the synaptic (AChE-S) variants in CSF were assessed in parallel together with the regional brain AChE activity by C-11-PMP and PET. The AChE-S inhibition was 30-36% in CSF, which correlated well with the in vivo AChE inhibition in the brain. No significant AChE inhibition was observed in the placebo group. The increased level of the AChE-R protein was 16% higher than that of AChE-S. Both the AChE inhibition and the increased level of AChE-R protein positively correlated with the patient's performance in cognitive tests associated with visuospatial ability and attention. In conclusion, AChE levels in CSF closely mirror in vivo brain AChE levels prior to and after treatment with the cholinesterase inhibitors. A positive cognitive response seems to dependent on the AChE inhibition level, which is balanced by an increased protein level of the AChE-R variant in the patients.
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- Ljung, T., et al.
(författare)
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Parental schizophrenia and increased offspring suicide risk : exploring the causal hypothesis using cousin comparisons
- 2013
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Ingår i: Psychological Medicine. - New York, USA : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 43:3, s. 581-590
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known about suicide risk among offspring of parents hospitalized for schizophrenia and the mechanisms behind this association.Method: We applied a nested case-control design based on linkage of Swedish population-based registers. Among 12- to 30-year-old offspring, we identified 68 318 offspring with suicidal behavior (attempted and completed suicide) and their parents. Five healthy control-parent pairs were matched to each suicidal case-parent pair and conditional logistic regression used to obtain odds ratios (ORs). Further, to disentangle familial confounding from causal environmental mechanisms, we compared the population-based suicide risk with the risk found within full-cousins and half-cousins differentially exposed to parental schizophrenia.Results: Offspring of parents with schizophrenia had significantly increased suicide risk after accounting for socio-economic status, parental suicidal behavior and offspring mental illness [OR 1.68, 95% confidence interval (CI) 1.53-1.85]. Suicide risks in offspring of schizophrenic mothers and fathers were similar in magnitude; so were risks across different developmental periods. Importantly, offspring suicide risk remained essentially unchanged across genetically different relationships; offspring of siblings discordant for schizophrenia had equivalent risk increases within full-cousins (OR 1.96, 95% CI 1.66-2.31) and half-cousins (OR 1.69, 95% CI 1.17-2.44).Conclusions: Parental schizophrenia was associated with increased risk of offspring suicidal behavior, independent of gender of the schizophrenic parent, and persisting into adulthood. The suicide risk in offspring remained at a similar level when comparing genetically different relationships, which suggests that at least part of the association is due to environmental mechanisms. These findings should inspire increased attention to suicidal ideation and prevention efforts in offspring of parents with schizophrenia.
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