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Search: L773:1421 9824 > Winblad B

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1.
  • Algotsson, A, et al. (author)
  • Patients with Alzheimer's disease may be particularly susceptible to adverse effects of statins
  • 2004
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 17:3, s. 109-116
  • Journal article (peer-reviewed)abstract
    • In epidemiological, cross-sectional studies, treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) prevented to a large extent the development of Alzheimer’s disease (AD), but the results of randomized, placebo-controlled studies, focused on statin therapy in patients with ischemic heart disease (IHD), are at variance. Nonetheless, data from epidemiological, longitudinal studies in humans as well as studies on transgenic mouse models and cultured neuronal cell lines indicate that cholesterol may contribute to the pathogenesis of AD. Statins have proven therapeutic and preventive effects in IHD and other vascular diseases in man. They generally are well tolerated, but some adverse effects, probably due to antiproliferative and proapoptotic properties of the statins, are matters of concern. AD patients may be extrasusceptible to adverse effects of statins due to preexisting aberrations in signal transduction and energy metabolism in the neurons and a perturbed cholesterol metabolism in the brain. This problem might be addressed in randomized, double-blind studies with statins in AD. The statins differ from each other in several aspects, and they are not considered to be therapeutically interchangeable. It could be fruitful to use both a placebo and two different types of statins, i.e. an essentially hydrophilic statin and a lipophilic statin, in a double-blinded fashion, and to compare the effects on the cognitive decline in AD.
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2.
  • Brane, G, et al. (author)
  • The Gottfries-Bråne-Steen scale: validity, reliability and application in anti-dementia drug trials
  • 2001
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:1, s. 1-14
  • Journal article (peer-reviewed)abstract
    • Neuropsychological investigation using a comprehensive rating scale is important for the diagnosis and evaluation of dementia patients over time. Requirements for such a scale include accuracy, reliability, sensitivity of the scale over the disease course and simplicity for clinical use by a wide range of healthcare professionals. Ideally, the scale should also be capable of assessing the impact of pharmacological and non-pharmacological treatment regimens on the management of dementia patients. The Gottfries-Bråne-Steen (GBS) Scale is a comprehensive global assessment tool for evaluating dementia symptoms and is based on a semi-structured interview and observation of the patient. The scale consists of subscales measuring intellectual (12 items), emotional (3 items) and activities of daily living, primarily items of self-care (6 items); as well as 6 items of behavioral and psychological symptoms of dementia. This review describes the reliability, validity and sensitivity of the most recent version of the GBS scale since its original publication in 1982.
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4.
  • Fernaeus, SE, et al. (author)
  • White matter lesions impair initiation of FAS flow
  • 2001
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:1, s. 52-56
  • Journal article (peer-reviewed)abstract
    • Word fluency performance is known to rely on left frontal cortical regions and has also been shown to be affected by lesions in the white matter, which may be seen as white matter hyperintensities (WMH) on magnetic resonance imaging. However, word fluency may be divided into two independent components, initial and late performance, separated in time [J Clin Exp Neuropsychol 1998;20:137–143]. The purpose of the current study was to investigate the relationship between the two components of FAS fluency performance and WMH. Patients varying in degree of memory impairment participated: Alzheimer’s disease, mild cognitive impairment and subjective memory disorder. WMH were rated with the Scheltens scale in the periventricular and deep subcortical areas. Results demonstrated that WMH in this sample of patients may be summarized in two indices according to a principal factor analysis, one anterior factor mainly related to WMH in the frontal lobes and adjacent to ventricles, and a second posterior factor related to parietal and occipital WMH. The initial FAS performance was related to anterior WMH, in particular left frontal or lateral periventricular hyperintensities, whereas the late FAS performance was not related to any index of WMH.
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5.
  • Hansson, G, et al. (author)
  • Intact brain serotonin system in vascular dementia
  • 1996
  • In: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 7:4, s. 196-200
  • Journal article (peer-reviewed)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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6.
  • HILL, RD, et al. (author)
  • Visuospatial performance in very old demented persons: an individual difference analysis
  • 1995
  • In: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 6:1, s. 49-54
  • Journal article (peer-reviewed)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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7.
  • Jelic, V, et al. (author)
  • Donepezil treatment of severe Alzheimer's disease in nursing home settings. A responder analysis
  • 2008
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 26:5, s. 458-466
  • Journal article (peer-reviewed)abstract
    • <i>Background/Aims:</i> Our objective was to define clinically meaningful outcomes in donepezil versus placebo treatment in severe Alzheimer’s disease (AD) and to describe characteristics of responders. <i>Methods:</i> Analyses were performed on data from a 6-month, double-blind, parallel-group, placebo-controlled study on the efficacy of donepezil in 248 nursing home residents. Various individual responses were defined as stabilisation or improvement on the Severe Impairment Battery (SIB), Alzheimer’s Disease Cooperative Study-activities of daily living scale (ADCS-ADL), Mini-Mental State Examination, Neuropsychiatric Inventory (NPI) or Clinical Global Impression of Improvement. Three composite measures were defined by combining the individual response criteria on these outcomes. The impact of baseline disease severity and of concomitant use of psychotropic drugs was also analysed. <i>Results:</i> At 6 months, greater proportions of patients defined as responders to donepezil on individual efficacy measures showed significant stabilisation or improvement compared with placebo on the SIB (≧0, ≧4 or ≧7 points) and Mini-Mental State Examination (≧0 or ≧3 points), and positive trends on the ADCS-ADL-severe (≧3 points) and the NPI cluster based on mood items. All 3 composite measures of efficacy showed a significantly higher proportion of responders in the donepezil group. The responders had a similar distribution between the 2 subgroups of cognitive and functional disease severity at baseline. The donepezil-treated patients taking psychotropic drugs showed significantly greater improvement on the SIB, less deterioration on the ADCS-ADL, and had higher Clinical Global Impression of Improvement scores and a trend towards lower NPI scores. The baseline demographic and clinical profile did not differ between the non-responders and responders on the composite outcome measures. <i>Conclusion:</i> The results demonstrate that donepezil treatment of patients with severe AD consistently shows stabilisation or improvement across multiple outcome measures in individual patients, including cognitive, functional and behavioural symptoms.
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8.
  • Jelic, V, et al. (author)
  • Quantitative electroencephalography power and coherence in Alzheimer's disease and mild cognitive impairment
  • 1996
  • In: Dementia (Basel, Switzerland). - : S. Karger AG. - 1013-7424. ; 7:6, s. 314-323
  • Journal article (peer-reviewed)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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9.
  • Jonhagen, ME, et al. (author)
  • Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease
  • 1998
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 9:5, s. 246-257
  • Journal article (peer-reviewed)abstract
    • Nerve growth factor (NGF) is important for the survival and maintenance of central cholinergic neurons, a signalling system impaired in Alzheimer’s disease. We have treated 3 patients with Alzheimer’s disease with a total of 6.6 mg NGF administered continuously into the lateral cerebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient. The patients were extensively evaluated with clinical, neuropsychological, neurophysiological and neuroradiological techniques. Three months after the NGF treatment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuropsychology tests showed slight improvements. The amount of slow-wave cortical activity as studied by electroencephalography was reduced in the first 2 patients. Two negative side effects occurred with NGF treatment: first, a dull, constant back pain was observed in all 3 patients, which in 1 patient was aggravated by axial loading resulting in sharp, shooting pain of short duration. When stopping the NGF infusion, the pain disappeared within a couple of days. Reducing the dose of NGF lessened the pain. Secondly, a marked weight reduction during the infusion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol. Alternative routes of administration, and/or lower doses of NGF, perhaps combined with low doses of other neurotrophic factors, may shift this balance in favor of positive effects.
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10.
  • Karp, A, et al. (author)
  • Mental, physical and social components in leisure activities equally contribute to decrease dementia risk
  • 2006
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 21:2, s. 65-73
  • Journal article (peer-reviewed)abstract
    • Background: There is accumulating evidence in the literature that leisure engagement has a beneficial effect on dementia. Most studies have grouped activities according to whether they were predominantly mental, physical or social. Since many activities contain more than one component, we aimed to verify the effect of all three major components on the dementia risk, as well as their combined effect. Methods: A mental, social and physical component score was estimated for each activity by the researchers and a sample of elderly persons. The correlation between the ratings of the authors and the means of the elderly subjects' ratings was 0.86. The study population consisted of 776 nondemented subjects, aged 75 years and above, living in Stockholm, Sweden, who were still nondemented after 3 years and were followed for 3 more years to detect incident dementia cases. Results: Multi-adjusted relative risks (RRs) of dementia for subjects with higher mental, physical and social component score sums were 0.71 (95% CI: 0.49-1.03), 0.61 (95% CI: 0.42-0.87) and 0.68 (95% CI: 0.47-0.99), respectively. The most beneficial effect was present for subjects with high scores in all or in two of the components (RR of dementia = 0.53; 95% CI: 0.36-0.78). Conclusions: These findings suggest that a broad spectrum of activities containing more than one of the components seems to be more beneficial than to be engaged in only one type of activity
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