| 1. |
- Buchhave, Peder, et al.
(författare)
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Cube copying test in combination with rCBF or CSF A beta(42) predicts development of Alzheimer's disease
- 2008
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 25:6, s. 544-552
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aim: </i>The aim was to identify subjects with incipient Alzheimer’s disease (AD) among patients with mild cognitive impairment (MCI) using brief cognitive tests. <i>Methods: </i>A total of 147 MCI patients were followed for 4–6 years and the incidence of AD was 11.6%/year. At baseline, the cube copying test, clock drawing test, MMSE and measurements of regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) β-amyloid<sub>1–42</sub> (Aβ<sub>42</sub>) were performed. <i>Results: </i>The cube copying test, but not the clock drawing test, could predict AD among MCI patients with an area under the receiver operating characteristic curve of 0.64 (p < 0.01). The relative risk for future AD was increased in MCI subjects with impaired cube copying test (sex- and age-adjusted hazard ratio = 1.8, p < 0.05) and the incidence of AD was 18.2% in this subgroup. Combining the cube copying test with either rCBF or CSF Aβ<sub>42</sub> had additive effects on the risk assessment for future development of AD. MCI patients achieving high scores on both MMSE and cube copying test had a very low risk of developing AD (incidence of AD = 1.6%). <i>Conclusion: </i>In conclusion, combinations of the cube copying test with MMSE, rCBF and CSF Aβ<sub>42</sub> measurements can identify subgroups of MCI subjects with either substantially reduced or increased risk for future development of AD.
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| 2. |
- Hansson, Oskar, et al.
(författare)
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Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer's disease.
- 2009
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:2, s. 165-73
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to identify preclinical Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) using measurements of both regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) biomarkers. Baseline rCBF assessments ((133)Xe method) were performed in 70 patients with MCI who were cognitively stable for 4-6 years, 69 patients with MCI who subsequently developed AD, and 33 healthy individuals. CSF was collected at baseline and analyzed for beta-amyloid(1-42), total tau and phophorylated tau. In contrast to patients with stable MCI, those who subsequently developed AD had decreased rCBF in the temporo-parietal cortex already at baseline. The relative risk of future progression to AD was particularly increased in MCI patients with decreased rCBF in parietal cortex (hazard ratio 3.1, P<0.0001). Subjects with pathological levels of both CSF tau and beta-amyloid(1-42) were also at high risk of developing AD (hazard ratio 13.4, P<0.0001). The MCI patients with a combination of decreased parietal rCBF and pathological CSF biomarkers at baseline had a substantially increased risk of future development of AD, with a hazard ratio of 24.3 (P<0.0001), when compared to those with normal CSF biomarkers. Moreover, decreased parietal rCBF (but not CSF biomarkers) was associated with a more rapid progression to AD. In conclusion, the combination of rCBF and CSF biomarkers improves the risk assessment of progression to AD in patients with MCI.
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| 3. |
- Janciauskiene, Sabina, et al.
(författare)
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A link between sICAM-1, ACE and parietal blood flow in the aging brain.
- 2009
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 30:9, s. 1504-1511
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Tidskriftsartikel (refereegranskat)abstract
- A connection between Alzheimer's disease (AD) and endothelium pathology has been inferred from measured decreases in both blood flow and metabolism in the parietal and temporal cortex. However, it is not known whether these alterations are seen in normal aging. We performed regional cerebral blood flow (rCBF) measurements in 22 AD patients and in 44 non-demented subjects during a simple test of information processing speed. Cerebrospinal fluid (CSF) levels of angiotensin-converting enzyme (ACE) and the soluble form of intercellular adhesion molecule-1 (sICAM-1) were analyzed in non-demented subjects. We found correlations between sICAM-1 and ACE (p=0.004), and sICAM (but not ACE) and CSF/plasma albumin ratio (p<0.0001). Higher concentrations of sICAM-1 (>893ng/L) and ACE (>5.22microg/L) were exclusively associated with lower parietal blood flow (p<0.001). The rCBF patterns in the AD and non-demented subjects with biomarker levels above median showed similar reductions in the temporoparietal areas. Our findings provide evidence that elevated CSF sICAM-1 and ACE are associated with lower perfusion levels in the parietal cortex of cognitively intact elderly.
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| 4. |
- Johansson, Annica, 1969, et al.
(författare)
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Homocysteine levels in patients with Alzheimer's disease are influenced by the glutathione s-transferase omega-1 (GSTO1) gene
- 2005
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Ingår i: Haematologica Reports. - 1824-9337. ; 2005:1(3):June
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: A substantial body of literature confirms an association between elevated blood levels of homocysteine and cognitive dysfunction, including Alzheimer’s disease (AD). Oxidative stress is a risk factor for AD. Elevated homocysteine levels might partially reflect redox status; its remethylation to methionine is coordinated by the redox-sensitive enzyme methionine synthase. Glutathione S-transferase omega-1 (GSTO1) is protective against oxidative stress, and the polymorphism Ala140Asp modifies the age-of-onset of AD. Aim: To investigate whether the GSTO1 Ala140Asp polymorphism is related to homocysteine levels in AD patients. Methods: Plasma homocysteine levels and the GSTO1 polymorphism Ala140Asp were analysed in 244 consecutive patients with clinically diagnosed AD. Results: Homocysteine levels differed significantly between the three genotypes (p=0.002) analysis of variance, Durbin-Watson D Statistic. The levels were 11.8±3.6 µmol/L in patients with the Ala/Ala genotype (n=118), 13.5±5.0 µmol/L in the Ala/Asp group (n=105), and 14.1±6.0 µmol/L in patients with the Asp/Asp genotype (n=21). Carriers of at least one Asp allele showed significantly higher plasma homocysteine levels compared to non-carriers (p=0.002) two-sample t-test. Conclusion: The association between homocysteine levels and this GSTO1 polymorphism supports the suggestion that increased homocysteine in AD patients may be a consequence of oxidative stress.
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| 5. |
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| 6. |
- Subramaniyam, Devipriya, et al.
(författare)
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TNF-alpha-induced self expression in human lung endothelial cells is inhibited by native and oxidized alpha 1-antitrypsin
- 2008
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Ingår i: International Journal of Biochemistry & Cell Biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 40:2, s. 258-271
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cells are among the main physiological targets of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). In endothelial cells TNF-alpha elicits a broad spectrum of biological effects including differentiation, proliferation and apoptosis. alpha 1-antitrypsin (AAT), an endogenous inhibitor of serine proteases plays a vital role in protecting host tissue from proteolytic injury at sites of inflammation. Recently, it has been shown that AAT can be internalized by pulmonary endothelial cells, raising speculation that it may modulate endothelial cell function in addition to suppressing protease activity. Using Affymetrix microarray technology, real time PCR and ELISA methods we have investigated the effects of AAT on un-stimulated and TNF-alpha stimulated human primary lung microvascular endothelial cell gene expression and protein secretion. We find that AAT and TNF-alpha generally induced expression of distinct gene families with AAT exhibiting little activity in terms of inflammatory gene expression. Approximately 25% of genes up regulated by TNF-alpha were inhibited by co-administration of AAT including TNF-alpha-induced self expression. Surprisingly, the effects of AAT on TNF-alpha-induced self expression was inhibited equally well by oxidized AAT, a modified form of AAT, which lacks serine protease inhibitor activity. Overall, the pattern of gene expression regulated by native and oxidized AAT was similar with neither inducing pro-inflammatory gene expression. These findings suggest that inhibitory effects of native and oxidized forms of AAT on TNF-alpha stimulated gene expression may play an important role in limiting the uncontrolled endothelial cell activation and vascular injury in inflammatory disease.
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| 7. |
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| 8. |
- Warkentin, Siegbert, et al.
(författare)
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rCBF pathology in Alzheimer's disease is associated with slow processing speed
- 2008
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Ingår i: Neuropsychologia. - : Elsevier BV. - 1873-3514 .- 0028-3932. ; 46:5, s. 1193-1200
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Tidskriftsartikel (refereegranskat)abstract
- Decreased information processing speed (mental slowing) is a known sequelae of many brain disorders, and can be assessed by continuous naming tasks. Functional imaging studies have shown that pause and articulation times in continuous speech are normally associated with different brain regions, but knowledge about such association in dementia is lacking. We therefore tested the hypothesis that perfusion deficits in Alzheimer's disease (AD) are not only associated with slower processing, but also with these speech measures. Using regional cerebral blood flow (rCBF) measurements during the performance of a continuous colour and form-naming task, we found that naming speed was substantially slower in AD patients than in controls. This slower naming was exclusively determined by an increase in mean pause time, and only to a limited extent by articulation time. The increased pause time was uniquely associated with temporo-parietal rCBF reductions of the patients, while articulation was not. By contrast, the rCBF of healthy elderly control subjects was consistently accompanied by substantially shorter articulation and pause times, although the naming measures were not statistically associated with rCBF. These findings suggest that pause time (in contrast to articulation time) may serve as a sensitive measure in the assessment of information processing speed deficits in dementia, by virtue of its close association with brain pathology. (C) 2007 Elsevier Ltd. All rights reserved.
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