| 21. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Longitudinal cerebrospinal fluid biomarkers over four years in mild cognitive impairment.
- 2012
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908 .- 1387-2877. ; 30:4, s. 767-78
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) measurements of amyloid-β42 (Aβ42), total-tau (T-tau), and phosphorylated tau (P-tau) may be used to predict future Alzheimer's disease (AD) dementia in patients with mild cognitive impairment (MCI). The precise temporal development of these biomarkers in relation to clinical progression is unclear. Earlier studies have been hampered by short follow-up. In an MCI cohort, we selected 15 patients who developed AD (MCI-AD) and 15 who remained cognitively stable during 4 years of follow-up. CSF was sampled at three serial occasions from each patient and analyzed for Aβ peptides, the soluble amyloid-β protein precursor protein fragments sAβPPα and sAβPPβ, T-tau, P-tau, and chromogranin B, which is a protein linked to regulated neuronal secretion. We also measured, for the first time in MCI patients, an extended panel of Aβ peptides by matrix-assisted-laser-desorption/ionization time-of-flight mass spectrometry (MS). Most biomarkers were surprisingly stable over the four years with coefficients of variation below or close to 10%. However, MCI-AD patients decreased in CSF AβX₋₄₀ and chromogranin B concentrations, which may indicate a reduced number of functional neurons or synapses with disease progression. The MS Aβ peptide panel was more useful than any single Aβ peptide to identify MCI-AD patients already at baseline. Knowledge on these biomarkers and their trajectories may facilitate early diagnosis of AD and be useful in future clinical trials to track effects of disease modifying drugs.
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| 22. |
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| 23. |
- Nordlund, Arto, 1962, et al.
(författare)
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Cognitive profiles of incipient dementia in the Goteborg MCI study.
- 2010
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 30:5, s. 403-10
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Tidskriftsartikel (refereegranskat)abstract
- To study which cognitive profiles of incipient dementia strongest predict the conversion to Alzheimer's disease (AD) and mixed dementia (MD)/vascular dementia (VaD).
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| 24. |
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| 25. |
- Nordlund, Arto, 1962, et al.
(författare)
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Episodic memory and speed/attention deficits are associated with Alzheimer-typical CSF abnormalities in MCI
- 2008
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Ingår i: Journal of the International Neuropsychological Society. - 1355-6177. ; 14:4, s. 582-590
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Tidskriftsartikel (refereegranskat)abstract
- Mild cognitive impairment (MCI) is regarded as the prodromal stage of dementia disorders, such as Alzheimer's disease (AD). Objective: To compare the neuropsychological profiles of MCI subjects with normal concentrations of total tau (T-τ) and Aβ42 in CSF (MCI-norm) to MCI subjects with deviating concentrations of the biomarkers (MCI-dev). MCI-norm (N = 73) and MCI-dev (N = 73) subjects were compared to normal controls (N = 50) on tests of speed/attention, memory, visuospatial function, language and executive function. Results: MCI-norm performed overall better than MCI-dev, specifically on tests of speed and attention and episodic memory. When MCI-dev subjects were subclassified into those with only high T-tau (MCI-tau), only low Aβ42 (MCI-Aβ) and both high T-tau and low Aβ42 (MCI-tauAβ), MCI-tauAβ tended to perform slightly worse. MCI-tau and MCI-Aβ performed quite similarly. Conclusions: Considering the neuropsychological differences, many MCI-norm probably had more benign forms of MCI, or early non-AD forms of neurodegenerative disorders. Although most MCI-dev performed clearly worse than MCI-norm on the neuropsychological battery, some did not show any deficits when compared to age norms. A combination of CSF analyses and neuropsychology could be a step toward a more exact diagnosis of MCI as prodromal AD.
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| 26. |
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| 27. |
- Nordlund, Arto, 1962, et al.
(författare)
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Two year outcome of MCI subtypes and aetiologies in the Goteborg MCI study.
- 2010
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 81:5, s. 541-6
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to study the two year outcome of subjects diagnosed with Mild Cognitive Impairment (MCI). Two hundred and nine subjects diagnosed with MCI were examined with a comprehensive neuropsychological test battery and followed up after two years. After two years 34 subjects (16%) were lost for follow-up. Those subjects did not differ significantly in terms of MCI subclassification, MMSE score or age and education. Of the 175 subjects followed up, 8 (4.5%) had improved to normal, two with amnestic MCI, one from multiple domains MCI, three with single domain MCI and two without any significant impairment at baseline. Forty-four subjects (25%) had progressed to dementia. Out of these 35 were from the multidomain amnestic group and 9 from the multidomain non-amnestic group. The combination of Alzheimer-typical biomarkers (total-tau and amyloid beta) and multidomain amnestic MCI was the strongest predictor of progression to Alzheimer's disease, while vascular disease and multidomain amnestic MCI preceded mixed and vascular dementia. The results suggest that memory impairment alone, or impairment in any one cognitive domain alone, are rather benign conditions. Impairment in several cognitive domains is associated with a more severe outcome over two years. Also, 20% of the subjects who progressed to dementia, including Alzheimer's disease, did not show memory impairment at baseline, which suggests that memory impairment is not always the first symptom of even the most common dementia disorders.
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| 28. |
- Rolstad, Sindre, 1976, et al.
(författare)
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All cognitive systems but speed and visuospatial functions reduce the effect of CSF pathology on other systems.
- 2012
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Ingår i: Current Alzheimer research. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 9:9, s. 1043-1049
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Tidskriftsartikel (refereegranskat)abstract
- The concept of reserve can be conceived as differences in the ability to compensate for pathology by recruiting additional or alternative networks. The purpose of this study was to examine whether certain cognitive systems may compensate for the effect of CSF amyloid beta 42 (Aβ42) and total tau (T-tau) on other cognitive systems. Five hundred and nine participants underwent neuropsychological examination and lumbar puncture. Multiple regression was performed with interaction terms to test whether a cognitive system reduced the impact of CSF pathology on other systems. All cognitive systems except speed and visuospatial functions were associated with reduced effects of T-tau and Aβ42 on semantic memory, working memory and visuospatial abilities. The burden of Aβ42 was reduced more often than that of T-tau. Our results suggest that most cognitive systems may be beneficial to maintenance of cognitive performance despite CSF burden. The results support the notion of cognitive reserve.
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| 29. |
- Rolstad, Sindre, 1976, et al.
(författare)
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Amyloid-β₄₂ is associated with cognitive impairment in healthy elderly and subjective cognitive impairment.
- 2011
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Ingår i: Journal of Alzheimers Disorder. - 1387-2877. ; 26:1, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to predict cognitive performance on the basis of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau) and amyloid-β42 (Aβ42) in controls and patients at various impairment levels. Previous studies have found an association of CSF T-tau levels with cognitive symptoms, but it has been difficult to relate Aβ to cognition, and it has thus been hypothesized that Aβ reaches a plateau level prior to cognitive symptoms. A comprehensive battery of neuropsychological tests was subjected to factor analysis to yield aggregated cognitive domains. Linear regression models were performed for the total sample of the Gothenburg MCI study (n = 435) and for each level of impairment. Aβ42 and T-tau accounted for a significant proportion of performance in all cognitive domains in the total sample. In controls (n = 60) and patients with subjective cognitive impairment (n = 105), Aβ42 predicted a significant proportion of semantic and working memory performance. For patients with mild cognitive impairment (n = 170), T-tau had the most pronounced impact across cognitive domains, and more specifically on episodic memory, visuospatial, and speed/executive performance. For patients with dementia (n = 100), the most pronounced impacts of Aβ42 were found in episodic memory and visuospatial functioning, while T-tau was substantially associated with episodic memory. Our results suggest that cognition is related to CSF biomarkers regardless of impairment level. Aβ42 is associated with cognitive functions from a potentially early to a later disease phase, and T-tau is more indicative of performance in a later disease phase.
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| 30. |
- Rolstad, Sindre, 1976, et al.
(författare)
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Biomarkers in relation to cognitive reserve in patients with mild cognitive impairment--proof of concept.
- 2009
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 27:2, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The concept of the cognitive reserve (CR) posits that factors such as education enable compensation for the effect of brain pathology. Consequently, pathology should be more pronounced in individuals with higher CR before becoming clinically apparent. Biomarkers such as total tau (t-tau) and beta-amyloid 42 (Abeta42) may be surrogates for pathology in relation to CR in patients with neurodegenerative disease. OBJECTIVE: To examine the applicability of biomarkers as surrogates for pathology in relation to the CR in patients with mild cognitive impairment (MCI) either converting to dementia or remaining stable at follow-up. METHOD: Comparisons of baseline t-tau, Abeta42, educational years and global cognition for MCI patients either converting to dementia (n = 57) or remaining stable (n = 91) were made. Patients converting to dementia were grouped on the basis of educational level and compared considering biomarkers and neuropsychological tests. RESULTS: Stable MCI patients were better educated, performed better cognitively, had higher Abeta42 levels and lower levels of t-tau. Converting MCI patients with higher education had lower levels of Abeta42 and performed equally in neuropsychological tests compared to those with lower education. CONCLUSION: Our results suggest that highly educated MCI patients subsequently converting to dementia display more amyloid pathology.
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