| 1. |
- Farde, L, et al.
(författare)
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PET study of the M1-agonists [11C]xanomeline and [11C]butylthio-TZTP in monkey and man
- 1996
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Ingår i: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 7:4, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- Xanomeline, a substituted TZTP, is a new M<sub>1</sub> selective muscarinic agonist in clinical trials for Alzheimer''s disease. The brain uptake of [<sup>11</sup>C]xanomeline and the analog [<sup>11</sup>C]butylthio-TZTP was examined by positron emission tomography (PET). Radioactivity accumulated most markedly in the neocortex and the striatum. Pharmacological characterization in vitro and in cynomolgus monkeys in vivo by PET indicated specific [<sup>11</sup>C]butylthio-TZTP binding to muscarinic receptors and to sigma-1 recognition sites. More than 5% of the radioactivity was in the human brain 5 min after i.v. injection of [<sup>11</sup>C]xanomeline or [<sup>11</sup>C]butylthio-TZTP. This high brain uptake may be clinically advantageous in the sense that substituted TZTP may induce central muscarinic agonist effects at a dose level for which there is a low risk of peripheral side-effects.
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| 2. |
- Hansson, G, et al.
(författare)
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Intact brain serotonin system in vascular dementia
- 1996
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Ingår i: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 7:4, s. 196-200
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Tidskriftsartikel (refereegranskat)abstract
- Pre- and postsynaptic elements of the 5-hydroxytryptamine (5-HT, serotonin) system were studied in a control group and in patients with vascular dementia (VAD). The 5-HT uptake site was used as a presynaptic marker for 5-HT terminals and 5-HT1A and 5HT2 receptors were used as postsynaptic markers. The binding sites were quantified with radioligand binding techniques, where the radioligands used were [<sup>3</sup>H]paroxetine, [<sup>3</sup>H]8-OH-DPAT and [<sup>3</sup>H]ketanserin, respectively. The presynaptic uptake site was studied in frontal and temporal cortices and caudate nucleus. 5-HT1A and 5-HT2 receptors were studied only in frontal and temporal cortices. There were no differences between control and VAD groups in any of the regions investigated with respect to the number of binding sites (B<sub>max</sub>) and binding affinity (K<sub>d</sub>). This indicates that both pre- and postsynaptic parts of the 5-HT system are intact in these brain areas in VAD.
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| 3. |
- HILL, RD, et al.
(författare)
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Visuospatial performance in very old demented persons: an individual difference analysis
- 1995
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Ingår i: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 6:1, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- This study examines selected demographic, psychometric, and biological measures as predictors of visuospatial performance in a sample of 98 persons with mild to moderate dementia. Visuospatial performance was measured using standardized neuropsychology instruments, namely: Poppelreuter''s figures, the clock test, and block design. Although multiple measures were initially correlated with performance on the selected visuospatial tests, the Mini-Mental State Examination was the exclusive predictor of Poppelreuter''s figures and the clock test scores. For block design, years of education also contributed to the prediction model, but only among mildly demented persons. These results suggest that disease severity plays a dominant role in the prediction of visuospatial performance in dementia, particularly in more advanced stages of the disease. The differential role of education in predicting block design performance in mild vs. moderate dementia was also highlighted.
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| 4. |
- Jelic, V, et al.
(författare)
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Quantitative electroencephalography power and coherence in Alzheimer's disease and mild cognitive impairment
- 1996
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Ingår i: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 7:6, s. 314-323
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Tidskriftsartikel (refereegranskat)abstract
- In this study the best combination of quantitative electroencephalographic variables (qEEG) for the discrimination of groups with mild to moderate Alzheimer''s disease (AD), mild cognitive impairment and healthy subjects was defined and related to neuropsychological performance. The study population included 18 patients with mild to moderate probable AD, 19 subjects with objective memory disturbances, 17 subjects with subjective memory complaints who did not have clinical evidence of memory disturbance, and 16 healthy controls. AD patients had significantly increased theta and decreased alpha relative power, mean frequency, and temporoparietal coherence. There was no significant difference in the mean frequency in the left temporal region between AD patients and subjects with objective memory disturbances. Temporoparietal coherence appeared as a discriminant variable together with alpha and theta relative power only between AD patients and controls, giving 77.8% sensitivity and 100% specificity. Significant correlations between regional changes in qEEG variables and cognitive functions were found.
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| 5. |
- Johansson, M, et al.
(författare)
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Steady-state pharmacokinetics of tacrine in long-term treatment of Alzheimer patients
- 1996
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Ingår i: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 7:2, s. 111-117
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Tidskriftsartikel (refereegranskat)abstract
- The pharmacokinetics of the cholinesterase inhibitor tacrine was studied in 5 Alzheimer patients during 12–31 months of treatment. A mean average steady-state concentration in plasma ranging from 1.1 to 30ng/ml was obtained with doses ranging from 40 to 160 mg of tacrine daily. During treatment with 80 mg daily a maximal plasma concentration of tacrine (8.7 ± 0.6 ng/ml) was obtained 1.3 ± 0.2 h after intake of the morning dose. The mean elimination half-life was estimated at 5–7 h and remained unchanged when the tacrine dose was increased. The plasma concentration of tacrine was stable during long-term treatment with tacrine and no tolerance was observed regarding its cholinesterase inhibitory effect. A maximal 40% inhibition of plasma cholinesterase (ChE) activity and 60% inhibition of acetylcholinesterase activity in red blood cells was measured following treatment with the highest dose of 160 mg tacrine daily. A significant correlation was obtained between the plasma concentration of tacrine and the inhibition of ChE activity (p < 0.001). The tacrine concentration in CSF was measured in each patient on 1–3 occasions during the treatment and the ratio CSF/plasma concentration was estimated to be 0.47 ± 0.09 (n = 11).
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| 6. |
- JULIN, P, et al.
(författare)
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Clinical diagnosis of frontal lobe dementia and Alzheimer's disease: relation to cerebral perfusion, brain atrophy and electroencephalography
- 1995
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Ingår i: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 6:3, s. 142-147
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Tidskriftsartikel (refereegranskat)abstract
- The regional cerebral blood flow, brain atrophy, white matter changes and neurophysiologic changes were evaluated in 28 patients with a clinical diagnosis of probable Alzheimer''s disease (AD) and in 8 patients with a clinical diagnosis of frontal lobe dementia (FLD) using single photon emission computed tomography, magnetic resonance imaging and electroencephalography (EEG). We found that FLD patients had more severe frontal blood flow reduction and less severe parietal blood flow reduction compared to AD patients. Among patients with mild dementia the EEG changes were less severe in the FLD group. No significant differences were found in white matter changes or in regional atrophy.
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| 7. |
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