| 1. |
- Andersson, Maria A, et al.
(författare)
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The cognitive profile and CSF biomarkers in dementia with Lewy bodies and Parkinson's disease dementia.
- 2011
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Ingår i: International journal of geriatric psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 26:1, s. 100-5
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Tidskriftsartikel (refereegranskat)abstract
- Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) may be viewed as different points on a continuum reflecting the regional burden and distribution of pathology. An important clinical consideration is overlapping Alzheimer's disease (AD) pathology, since it has been reported that associated AD pathology in DLB shortens survival and leads to a more rapid cognitive decline. We aimed to investigate cerebrospinal fluid (CSF) biomarkers and the associated cognitive profile in DLB and PDD.
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| 2. |
- Hansson, Oskar, et al.
(författare)
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Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment.
- 2010
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 31:3, s. 357-67
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have shown a marked decrease of beta-amyloid(42) (Abeta(42)) in the cerebrospinal fluid (CSF) of patients with incipient Alzheimer's disease (AD). However, studies on Abeta in plasma are contradictory, and show very marginal differences between patients and controls. Here, we analyzed plasma samples using a new multiplex immunoassay for simultaneous analysis of Abeta(1-40), Abeta(n-40), Abeta(1-42), and Abeta(n-42). The plasma samples were obtained at baseline from two independent cohorts of patients with mild cognitive impairment (MCI) and age-matched controls. In the first cohort, 41% of the 117 MCI cases converted to AD during a clinical follow-up period of 4-7 years. In the second cohort, 14% of the 110 MCI subjects developed AD during a clinical follow-up period of 2-4 years. None of the plasma Abeta isoforms differed between MCI patients that subsequently developed AD and healthy controls or stable MCI patients. The Cox proportional hazards model did not reveal any differences in the probability of progression from MCI to AD related to plasma Abeta levels. In contrast, low levels of Abeta(1-42) in CSF were strongly associated with increased risk of future AD. The absence of a change in plasma Abeta in incipient AD, despite the marked change in CSF, may be explained by the lack of a correlation between the levels of Abeta(1-42) in CSF and plasma. In conclusion, the results show that CSF biomarkers are better predictors of progression to AD than plasma Abeta isoforms.
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| 3. |
- Mulugeta, Ezra, et al.
(författare)
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Cerebrospinal Fluid Levels of sAPPα and sAPPβ in Lewy Body and Alzheimer's Disease: Clinical and Neurochemical Correlates.
- 2011
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Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2011
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Tidskriftsartikel (refereegranskat)abstract
- We measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid precursor protein (APP; sAPPα sAPPβ) and other CSF biomarkers in 107 patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB), Parkinson's disease dementia (PDD), and normal controls (NC) using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No differences were observed in sAPPα and sAPPβ levels between the groups. Significant correlations were observed between sAPPα and sAPPβ and between sAPPβ and Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPα and sAPPβ levels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPα correlated with p-Tau and sAPPβ with Aβ40. The differential association between sAPPα and sAPPβ with Aβ and Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD.
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| 4. |
- Mulugeta, Ezra, et al.
(författare)
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CSF amyloid {beta}38 as a novel diagnostic marker for dementia with Lewy bodies.
- 2011
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 82:2, s. 160-4
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Tidskriftsartikel (refereegranskat)abstract
- Background The clinical distinction between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is sometimes difficult, particularly in mild cases. Although CSF markers such as amyloid β42 (Aβ42) and P-tau can distinguish between AD and normal controls, their ability to distinguish between AD and DLB is not adequate. Objective This study aims to investigate whether CSF markers, in particular levels of Aβ38, can differentiate between mild AD and DLB. Methods 85 individuals were included after standardised diagnostic procedures: 30 diagnosed as probable AD, 23 probable DLB, 20 probable Parkinson's disease dementia and 12 non-demented control subjects. CSF levels of Aβ38, Aβ40 and Aβ42 were determined using commercially available ultra-sensitive multi-array kit assay (MSD) for human Aβ peptides. Total tau (T-tau) and phosphorylated tau (P-tau) were analysed using ELISA (Innotest). In addition, combinations (Aβ42/Aβ38, Aβ42/Aβ40, Aβ42/P-tau and Aβ42/Aβ38/P-tau) were assessed. Results Significant between group differences were found for all CSF measures, and all except Aβ40, Aβ42 and Aβ42/P-tau differed between AD and DLB. The Aβ42/Aβ38 ratio was the measure that best discriminated between AD and DLB (AUC 0.765; p<0.005), with a sensitivity of 78% and a specificity of 67%. Conclusion This study suggests that the level of Aβ38 can potentially contribute in the diagnostic distinction between AD and DLB when combined with Aβ42. Single measures had low diagnostic accuracy, suggesting that developing a panel of markers is the most promising strategy. Studies with independent and larger samples and a priori cut-offs are needed to test this hypothesis.
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| 5. |
- Stomrud, Erik, et al.
(författare)
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Correlation of longitudinal cerebrospinal fluid biomarkers with cognitive decline in healthy older adults.
- 2010
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Ingår i: Archives of neurology. - : American Medical Association (AMA). - 1538-3687 .- 0003-9942. ; 67:2, s. 217-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Abnormal cerebrospinal fluid (CSF) biomarker levels predict development of Alzheimer disease with good accuracy and are thought to precede cognitive deterioration. OBJECTIVE: To investigate whether changes in CSF biomarker levels over time in healthy older adults are associated with a concurrent decline in cognitive performance. DESIGN: Retrospective analysis of longitudinal CSF biomarker levels and clinical data. SETTING: A combined academic dementia disorder research center and dementia clinic. PARTICIPANTS: Thirty-seven cognitively healthy older volunteers (mean age, 73 years). MAIN OUTCOME MEASURES: Longitudinal CSF total tau protein, hyperphosphorylated tau protein 181, and beta-amyloid(1-42) protein levels and cognitive assessments at baseline and at follow-up 4 years later. RESULTS: Low levels of CSF beta-amyloid(1-42) protein at follow-up were associated with decreased delayed word recall score on the Alzheimer Disease Assessment Scale-cognitive subscale (r(s) = -0.437, P < .01) and with slower results on A Quick Test of Cognitive Speed (r(s) = -0.540, P < .001). Individuals with a decrease during the 4-year study of 15% or more in CSF beta-amyloid(1-42) protein level performed worse on the Alzheimer Disease Assessment Scale-cognitive subscale delayed word recall (z = -2.18, P < .05) and A Quick Test of Cognitive Speed (z = -2.35, P < .05) at follow-up. An increase over time of 20% or more in CSF hyperphosphorylated tau protein 181 level correlated with slower results on A Quick Test of Cognitive Speed at follow-up (z = -2.13, P < .05). Furthermore, the presence of the APOE-epsilon4 (OMIM 107741) allele was associated with a greater longitudinal decrease in CSF beta-amyloid(1-42) protein level (chi(2) = 10.47, P < .05) and with a higher CSF total tau protein level at follow-up (chi(2) = 8.83, P < .05). No correlation existed between baseline CSF biomarker levels and baseline or follow-up cognitive scores. CONCLUSIONS: In this group of healthy older adults, changes in CSF biomarker levels previously associated with Alzheimer disease correlated with a decline in cognitive functions. Changes in CSF biomarker levels may identify early neurodegenerative processes of Alzheimer disease.
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| 6. |
- Sämgård, Kajsa, et al.
(författare)
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Cerebrospinal fluid total tau as a marker of Alzheimer's disease intensity.
- 2010
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Ingår i: International journal of geriatric psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 25:4, s. 403-10
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this longitudinal study was to test the hypothesis that CSF biomarkers in AD patients also may be forward-looking measures that are associated not only with the degree and profile of cognitive impairment but also with changes in cognition over time.
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| 7. |
- Wallin, Å K, et al.
(författare)
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CSF biomarkers predict a more malignant outcome in Alzheimer disease.
- 2010
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Ingår i: Neurology. - 1526-632X. ; 74:19, s. 1531-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate if patterns of CSF biomarkers (T-tau, P-tau, and Abeta42) can predict cognitive progression, outcome of cholinesterase inhibitor (ChEI) treatment, and mortality in Alzheimer disease (AD). METHODS: We included outpatients with AD (n = 151) from a prospective treatment study with ChEI. At baseline, patients underwent cognitive assessments and lumbar puncture. The patients were assessed longitudinally. The 5-year survival rate was evaluated. CSF-Abeta42, T-tau, and P-tau were analyzed at baseline. K-means cluster analysis including the 3 CSF biomarkers was carried out. RESULTS: Cluster 1 contained 87 patients with low levels of Abeta42 and relatively low levels of T-tau and P-tau. Cluster 2 contained 52 patients with low levels of Abeta42 and intermediate levels of T-tau and P-tau. Cluster 3 contained 12 patients with low levels of Abeta42 and very high levels of CSF T-tau and P-tau. There were no differences between the clusters regarding age, gender, years of education, baseline instrumental activities of daily living, or APOE genotype. Even though there was no difference between cluster 3 and the other clusters in disease duration or global rating, the patients in cluster 3 performed worse on cognitive tests already at baseline. Patients in cluster 3 exhibited a very poor outcome of ChEI treatment. Finally, cognition deteriorated faster over time and the mortality rate was substantially increased in cluster 3. CONCLUSION: A subgroup of patients with Alzheimer disease with extreme levels of CSF biomarkers exhibits worse clinical outcomes over time, including faster progression of cognitive deficits, no response to ChEI treatment, and a higher mortality.
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| 8. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Low Incidence of Post-Lumbar Puncture Headache in 1,089 Consecutive Memory Clinic Patients
- 2010
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Ingår i: European Neurology. - : S. Karger AG. - 1421-9913 .- 0014-3022. ; 63:6, s. 326-330
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine the incidence of post-lumbar puncture headache (PLPH) in patients admitted for cognitive disturbances. Methods: The incidence of PLPH and other general (subdural hematoma, meningitis, encephalitis) or local (local pain, spinal hematoma, local infection) complications was evaluated in 1,089 consecutive patients (aged 23-89 years) who underwent lumbar puncture as a part of the routine diagnostic evaluation between February 2001 and March 2007 at a specialized memory clinic. Results: 28 (2.6%) of the patients reported PLPH of mild severity. No other local or general complications occurred. Conclusions: The incidence of PLPH in patients with cognitive disturbances is low and CSF analyses can thus be part of the diagnostic work-up at memory clinics. Copyright (C) 2010 S. Karger AG, Basel
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