| 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. |
- Liu, X, et al.
(författare)
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Synapse density related to cerebral blood flow and symptomatology in frontal lobe degeneration and Alzheimer's disease
- 1999
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:Suppl 1, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- In order to evaluate the functional significance of synaptic pathology, synaptic density was quantitated and related to clinical symptomatology and regional cerebral blood flow (rCBF) in 8 patients with frontal lobe degeneration of non-Alzheimer type (FLD) and 19 patients with Alzheimer's disease (AD). Synaptic density was measured in all layers of prefrontal and parietal cortex. The clinical picture of FLD was dominated by a frontal lobe syndrome with changes in personality and behavior, while AD was dominated by temporoparietal symptoms. This parallels the finding of frontal rCBF reductions in FLD patients and temporoparietal reductions in AD patients. Synaptic density was significantly decreased in both FLD and AD, with a regional severity which closely correlated with that of the degeneration, symptomatology and rCBF deficit. The results suggest that synaptic pathology is a likely cause of clinical symptoms and regional metabolic decrement in dementia.
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| 3. |
- Sun, Yongxin, et al.
(författare)
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Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer's disease.
- 2003
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 16:3, s. 136-144
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that a number of molecules associated with inflammation are involved in the pathogenesis of Alzheimer's disease (AD). We measured the levels of alpha1-antichymotrypsin (ACT), alpha1-antitrypsin (AAT), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and oxidised low-density lipoprotein (oxLDL) in matched cerebrospinal fluid (CSF) and plasma of 141 patients with probable AD. We found a significant relationship between CSF and plasma levels of ACT (r = 0.4, p < 0.001), IL-6 (r = 0.74, p < 0.001), MCP-1 (r = 0.71, p < 0.001), and a borderline relationship between CSF and plasma oxLDL (r = 0.22, p < 0.05). In addition, linear regression analysis revealed a positive correlation between levels of CSF-ACT and oxLDL (p < 0.001), but an inverse relation between levels of CSF ACT, CSF AAT and MCP-1 (p < 0.001). A significant correlation was also found between levels of CSF ACT, oxLDL and the ratio of CSF to serum albumin, which is used as a measure of the blood-brain barrier function. Our data extend previous reports regarding the inflammatory markers in the plasma and CSF of patients with AD and provide good evidence that levels of ACT, IL-6, MCP-1 and oxLDL in plasma and CSF might be candidates as biomarkers for monitoring the inflammatory process in AD.
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| 4. |
- Warkentin, Siegbert, et al.
(författare)
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Functional activation of the frontal lobes. Regional cerebral blood flow findings in normals and in patients with frontal lobe dementia performing a word fluency test
- 1993
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Ingår i: Dementia (Switzerland). - : S. Karger AG. - 1013-7424. ; 4:3-4, s. 188-191
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Tidskriftsartikel (refereegranskat)abstract
- The present study examined the utility of the Word Fluency Test (WFT) as a frontal-lobe-activating test in brain imaging. Regional cerebral blood flow (rCBF) was measured during rest and during the WFT in 49 healthy volunteers and in 15 patients with frontal lobe dementia (FLD). The results showed a highly significant frontal lobe activation in 85% of the normal subjects. This finding was not related to age or to the level of performance on the WFT. A significant frontal activation was seen in 13 of the 15 FLD patients. The frontal flow increase did not reach normal levels, and was not related to age, illness duration or severity of clinical symptoms. The results suggest that the WFT is an ideal test to use in conjunction with functional imaging in normals as well as in patients with organic dementia.
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| 5. |
- Warkentin, Siegbert, et al.
(författare)
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Functional imaging of the frontal lobes in organic dementia. Regional cerebral blood flow findings in normals, in patients with frontotemporal dementia and in patients with Alzheimer's disease, performing a word fluency test
- 1997
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 8:2, s. 105-109
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Tidskriftsartikel (refereegranskat)abstract
- Patterns of functional cortical activation were studied by means of regional cerebral blood flow measurements, performed during rest and during a word fluency task in normal subjects (n = 22), in patients with Alzheimer's disease (n = 17), and in patients with frontotemporal dementia (n = 15). Although all groups showed a significant activation of the Broca's area during word production, the activation of the dorsolateral prefrontal cortex was clearly subnormal in both dementia groups. The frontal dysfunction was not explained by number of words produced, illness duration, or age. Thus, the results demonstrate that the word fluency task is a sensitive measure of frontal lobe function, and its incorporation in imaging studies may facilitate the detection of subtle functional impairment of the frontal lobes in organic dementia.
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| 6. |
- Warkentin, Siegbert, et al.
(författare)
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Regional Cerebral Blood Flow in Alzheimer's Disease: Classification and Analysis of Heterogeneity.
- 2004
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 17:3, s. 207-214
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Tidskriftsartikel (refereegranskat)abstract
- Neural networks have been successfully applied to brain perfusion images to classify patients with Alzheimer’s disease from normal or other patient populations. Given the recognition that Alzheimer’s disease constitutes a heterogeneous disorder, the identification of subgroups sharing common functional brain deficits would constitute a further improvement in the utility of such methods. Therefore, we aimed to investigate whether neural networks could discriminate cortical perfusion deficits of patients with Alzheimer’s disease from normal brain perfusion. A second step was to identify subgroups of patients sharing similar perfusion deficits. The study population consisted of one group of 92 normal healthy subjects and one group of 132 patients with mild-to-moderate Alzheimer’s disease. The patients were diagnosed according to established criteria (DSM-IV and NINCDS-ADRDA). Regional cerebral blood flow was assessed by the non-invasive <sup>133</sup>Xe inhalation method, using a 64-detector system for measurements of blood flow in superficial cortical areas. The regional blood flow values were used as the only input to artificial neural networks with multilayer Perceptron architecture. The networks were trained using the back-propagation updating algorithm. A fourfold cross validation procedure was used in order to obtain the most reliable performance of the networks. The performance of the neural network, measured as the area under the receiver-operating characteristic curve, was 0.94, with a sensitivity for Alzheimer’s disease of 86% at a specificity of 90%. An analysis of the relative importance of cortical areas in the discrimination showed that left parietal areas were more important than the right homologous ones. A clustering analysis of the Alzheimer patients identified three or four subgroups of patients with clearly different combinations of blood flow pathology. A consistent finding in all subgroups was a significant deficit in temporoparietal blood flow of both hemispheres. Distinct group differences were seen in frontal, central and occipital areas with different combinations of involvement. This is the first study in which neural networks have been applied to brain perfusion images obtained with the <sup>133</sup>Xe inhalation method. The results demonstrate that a classification of patients with Alzheimer’s disease obtained with this method is compatible with the best results obtained with other brain imaging methods. The identification of clearly distinguishable patterns of blood flow pathology in subgroups of patients lends further support to the notion that Alzheimer’s disease is a heterogeneous disorder.
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