| 1. |
- Boström, Fredrik, et al.
(författare)
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CSF Mg and Ca as diagnostic markers for dementia with Lewy bodies.
- 2008
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:8, s. 1265-1271
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence implicates a role for altered metal homeostasis in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, few investigations have addressed this issue in dementia with Lewy bodies (DLB). The aim of the present study was to investigate metal concentrations in cerebrospinal fluid (CSF) and plasma from patients with DLB and other neurodegenerative disorders. To that end, CSF and plasma samples were collected from 29 patients with DLB, 174 patients with AD, 90 patients with AD with minor vascular components, and 51 healthy volunteers. Total concentrations of Mg, Ca, Mn, Fe, Cu, Zn, Rb, Sr, and Cs were determined using mass spectrometry. Patients with DLB had elevated Ca and Mg levels in CSF and Mg levels in plasma as compared to all other groups (p<0.001). Furthermore, a combination of CSF-Mg and CSF-Ca could distinguish DLB from AD with a sensitivity of 93% and a specificity of 85%. Cu levels in both CSF and plasma tended to be higher in DLB compared to the other groups, but these trends failed to reach significance after correction for multiple comparisons. Mn, Fe, Zn, Rb, and Sr concentration in CSF or plasma were similar in all groups. The observed elevations of CSF-Mg, CSF-Ca and CSF-Cu may contribute to or be associated with the neurodegenerative process in DLB. Furthermore, determination of CSF-Mg and CSF-Ca concentration may be a valuable tool in distinguishing DLB from AD.
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| 2. |
- 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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| 3. |
- Buchhave, Peder, et al.
(författare)
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Longitudinal study of CSF biomarkers in patients with Alzheimer's disease.
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:Suppl 3, s. 337-337
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The CSF biomarkers tau and Abeta42 can identify patients with AD, even during the preclinical stages. However, previous studies on longitudinal changes of tau and Abeta42 in individual patients with AD and elderly controls report somewhat inconsistent results. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the levels of tau and Abeta42 at baseline and after 1 year in 100 patients with AD. In a second cohort of 45 AD patients we measured the CSF biomarkers at baseline and after 2 years. Moreover, in 34 healthy elderly controls the CSF biomarkers were followed for 4 years. The baseline levels of tau were increased with >60% in AD patients compared to controls (p<0.001), while baseline Abeta42 levels were decreased with >50% (p<0.001). In the AD group followed for 2 years, tau increased with 16% compared to the baseline levels (p<0.05). However, the levels of tau were stable over 4 years in the controls. The levels of Abeta42 did not change significantly over time in any of the groups. In the patients with AD, tau was moderately associated with worse cognitive performance already at baseline (p<0.05). CONCLUSIONS/SIGNIFICANCE: Tau and Abeta42 in CSF seem to reflect the underlying disease state in both early and late stages of AD. The slight increase in tau over time observed in the patients with AD is modest when compared to the relatively large difference in absolute tau levels between AD patients and controls. Therefore, these markers maintain their usefulness as state markers over time and might serve as surrogate markers for treatment efficacy in clinical trials.
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| 4. |
- Stomrud, Erik, et al.
(författare)
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Cerebrospinal fluid biomarkers predict decline in subjective cognitive function over 3 years in healthy elderly
- 2007
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 24:2, s. 118-24
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether cerebrospinal fluid (CSF) biomarkers can predict cognitive decline in healthy, elderly individuals as they have been shown to do in cognitively impaired patient samples. Methods: In this study, 57 controls were tested for CSF biomarkers at baseline and then cognitively followed over 3 years. Results: Low levels of baseline beta-amyloid 1 - 42 (A beta 42) were associated with development of subjective memory impairment affecting quality of life (memQoL), with a worse Mini Mental Status Examination score and with inability to live in regular housing at follow-up ( p < 0.05). The combination of baseline A beta 42 and phosphorylated tau (P-tau) was found to predict development of pathological memQoL with a sensitivity of 71.4% and a specificity of 75.7 (< 0.01). Conclusion: Low A beta 42 and combined A beta 42 and P-tau predicted subjective cognitive decline in healthy individuals. In summary, this study shows that already in the clinically normal population Alzheimer-disease-related biological signs might be detectable. Copyright (c) 2007 S. Karger AG, Basel.
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| 5. |
- Stomrud, Erik
(författare)
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Neurodegenerative Biomarkers in Healthy Elderly - with special reference to the preclinical pattern of biological and cognitive markers for Alzheimer’s disease
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by tau and amyloid brain pathology. With the gradual degeneration of neurons, cognitive symptoms will arise and the affected individual will eventually develop AD dementia. The neuropathologic hallmarks of AD have been observed also in cognitively healthy individuals, which has led to the assumption that the disorder has a long preclinical phase. Several biological markers for detecting and predicting AD have been validated over the years, where CSF biomarkers are one of the most recent and accurate markers. The generally perceived notion today is that these biological markers will be altered also in the preclinical phase. An additional aspect is that a review made in this thesis of the control samples in CSF articles, suggests that controls have been selected without efforts to minimize the misclassification of preclinical AD individuals. Therefore the aim of this study was to investigate biological and cognitive markers for AD in a group of cognitively healthy elderly individuals who were used as clinical control subjects in research studies. Setting: The study sample consisted of 62 cognitively healthy elderly individuals from a clinical control group. They were followed for 4.5 years at three occasions and underwent assessments of EEG activity and regional cerebral blood flow (rCBF) as well as repeated assessments of cognitive function and CSF biomarker levels. The CSF biomarkers were Aβ42, total tau (t-tau) and hyperphosphorylated tau (p-tau). The cognitive testing included among others the MMSE, the ADAS-cog, cognitive speed (AQT), and subjective memory impairment. Results: In the sample there were individuals with clinically pathological assessments on each separate biological marker. CSF Aβ42 levels predicted development of subjective memory impairment affecting quality of life at the 3 years follow-up and correlated with delayed word recall and cognitive speed at the 4.5 years follow-up. Additionally, the individuals with decreasing CSF Aβ42 levels during the follow-up performed cognitively worse than those with stable levels at the 4.5 years follow-up. CSF tau levels on the other hand correlated with an increase of the low-frequent theta activity on EEG and showed covariance with rCBF in the right medial frontal lobe and the left fronto-parieto-temporal area. In each case the correlations were stronger for p-tau levels compared to t-tau levels. Increase in theta activity was also correlated with slower cognitive speed. Discussion: In this group of cognitively healthy elderly individuals there were individuals with deteriorated cognitive and biological markers associated with AD. These markers further correlated to one another in specific patterns, where it was the known AD-associated changes of the markers (i.e. low CSF Aβ42, high CSF t-tau and p-tau, decreased EEG rhythm, and decreased rCBF) that were primarily related. The findings could imply that the biomarkers might indicate early neurodegenerative changes of the brain and that these changes could be detectable before extensive cognitive impairment. The findings could also suggest that preclinical AD might be present in this “healthy” study sample. Hence, pathological processes prevailing in AD might bridge the clinically created arbitrary division of normal and non-normal aging of the brain.
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