| 1. |
- Bjerke, Maria, 1977, et al.
(författare)
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Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid.
- 2010
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Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2010
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Tidskriftsartikel (refereegranskat)abstract
- Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (Abeta(42)). However, a high discrepancy between different centers in measured Abeta(42) levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured Abeta(42) level. Methods. Aliquots of CSF samples were either treated differently prior to Abeta(42) measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF Abeta(42) levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted.
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| 2. |
- Eckerström, Carl, et al.
(författare)
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Combination of Hippocampal Volume and Cerebrospinal Fluid Biomarkers Improves Predictive Value in Mild Cognitive Impairment.
- 2010
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 29:4, s. 294-300
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mild cognitive impairment (MCI) is a heterogeneous condition, and the prognosis differs within the group. Recent findings suggest that hippocampal volumetry and CSF biomarkers can be used to predict which MCI patients have an underlying neurodegenerative disorder. Objective: To examine the combined predictive value of hippocampal volume and CSF levels of total tau (T-tau) and beta-amyloid(42) (Abeta(42)) in stable and converting MCI patients. The participants (n = 68) included patients with MCI at baseline and who converted to dementia by the time of the 2-year follow-up (n = 21), stable MCI patients (n = 21) and healthy controls (n = 26). Methods: The Göteborg MCI study is a clinically based longitudinal study with biannual clinical assessments. Hippocampal volumetry was performed manually, based on data from the 0.5-tesla MRI investigations at baseline. Baseline CSF levels of T-tau and Abeta(42) were measured using commercially available, enzyme-linked immunosorbent assays. Results: The converting MCI group had significantly smaller left hippocampi, lower CSF Abeta(42) and higher T-tau compared to both the stable MCI group and the healthy controls. Multivariate analysis revealed that a combination of the variables outperformed the prognostic ability of the separate variables. Conclusions: Hippocampal volumes supplement the prognostic accuracy of CSF Abeta(42) and T-tau in MCI.
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| 3. |
- 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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| 4. |
- Jonsson, Michael, 1955, et al.
(författare)
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Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia.
- 2010
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Ingår i: International journal of geriatric psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 25:6, s. 588-95
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cerebral white-matter changes (WMCs) are frequently found in dementia and have been proposed to be related to vascular factors and a certain symptomatological profile. However, few studies have included both vascular factors and a broad spectrum of cognitive, neurological and psychiatric symptoms, easily detectable by the physician in the everyday clinical work. The objective was to study the relationships between WMCs on MRI/CT and neuropsychiatric symptoms and vascular factors in patients with cognitive impairment. METHODS: One hundred and seventy-six patients with Alzheimer's disease, vascular dementia, mixed dementia, and mild cognitive impairment were included. All patients underwent a standardized examination including medical history, clinical examinations, laboratory tests and brain imaging (CT or MRI). The identification and severity degree of WMCs was assessed blindly to clinical findings, using a semi-quantitative scale. For statistical analyses, patients were grouped based on absence or presence of WMCs. Significant variables in bivariate analyses were included as predictors in stepwise multiple logistic regression analyses. RESULTS: Bivariate analyses showed significant associations between WMCs and age, gender, blood pressure, hypertension, ischaemic heart disease and TIA/RIND. Furthermore, there were significant associations between WMCs and apathy, mental slowness, disinhibition, gait disturbance and focal neurologic symptoms. The multivariate logistic model revealed apathy, mental slowness and age as the most consistent predicting factors for WMCs, together with MRI as a radiological method for the detection of WMCs. CONCLUSIONS: The findings indicate that WMCs in patients with dementia are associated with a dysexecutive-related behavioural symptom profile, vascular factors related to small and large vessel diseases and age. Copyright (c) 2009 John Wiley & Sons, Ltd.
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| 5. |
- Jonsson, Michael, 1955, et al.
(författare)
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Cerebrospinal fluid biomarkers of white matter lesions - cross-sectional results from the LADIS study.
- 2010
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Ingår i: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 17:3, s. 377-382
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer's disease (AD) and subcortical vascular dementia. Methods: Fifty-three non-demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid beta, alpha- and beta-cleaved soluble amyloid precursor protein, total tau (T-tau), hyperphosphorylated tau (P-tau(181)), neurofilament light protein (NFL), sulfatide and CSF/Serum-albumin ratio. Results: Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P < 0.001). CSF sulfatide concentration displayed similar changes but less strongly. T-tau, P-tau(181) and the different amyloid markers as well as CSF/S-albumin ratio did not differ significantly between the groups. Conclusions: The association of increased CSF-NFL levels with increasing severity of WMLs in non-demented subjects suggests that NFL is a marker for axonal damage in response to small vessel disease in the brain. This manifestation may be distinct from or earlier than the neurodegenerative process seen in AD, as reflected by the lack of association between WMLs and AD biomarkers.
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| 6. |
- Landgren, Sara, 1980, et al.
(författare)
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No Association of VEGF Polymorphims with Alzheimer's Disease
- 2010
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 12:3, s. 224-228
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Tidskriftsartikel (refereegranskat)abstract
- The vascular hypothesis of Alzheimer's disease (AD) has brought the vascular endothelial growth factor (VEGF) into focus. The genomic region including the VEGF gene has been linked to AD and single nucleotide polymorphisms (SNPs) of the VEGF have in previous studies been associated with AD risk. To further evaluate these findings, we genotyped two SNPs in the VEGF gene (rs699947 [-2578]) and rs1570360 [-1154]) by TaqMan Allelic Discrimination in a study sample including AD patients (n = 801) and controls (n = 286). In a subgroup of the population these SNPs were analyzed in relation to APOE epsilon 4 genotype, to cerebrospinal fluid biomarkers (T-tau, P-tau, and beta(42)-Amyloid) as well as to neuropathological markers for AD (neurofibrillary tangles and senile plaques). No significant associations with risk for AD or any of the studied biomarkers could be found in this study, thus not supporting VEGF as being a major risk gene for AD.
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| 7. |
- Madureira, Sofia, et al.
(författare)
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Neuropsychological Predictors of Dementia in a Three-Year Follow-Up Period: Data from the LADIS Study
- 2010
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Ingår i: DEMENTIA AND GERIATRIC COGNITIVE DISORDERS. - 1420-8008. ; 29:4, s. 325-334
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: White matter changes (WMC) are related to cognitive deficits and dementia. Our aim was to determine the extent to which the performance in neuropsychological tests would be able to predict the clinical diagnosis of dementia. METHODS: The LADIS (Leukoaraiosis and Disability) is a prospective study that evaluates the impact of WMC on the transition of independent elderly to disability. The subjects were evaluated at baseline and yearly during 3 years with a comprehensive clinical, functional and neuropsychological protocol. At each visit, dementia was classified according to clinical criteria. The performance in the neuropsychological batteries was compared according to the clinical diagnosis of dementia. RESULTS: From the initially enrolled 639 subjects, 480 were evaluated at year 3. Dementia was diagnosed in 90 participants. The demented subjects had worse performance in almost all the baseline cognitive tests. Using receiver operating characteristic curves, we found that the Vascular Dementia Assessment Scale (VADAS) battery had higher sensitivity and specificity rates (area under the curve = 82%) to identify dementia compared with the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale. Worse performance on baseline MMSE (beta = 0.33; p < 0.001) and VADAS (beta = -0.07; p = 0.02) were predictors of dementia (regression analyses). CONCLUSION: Performance on the MMSE and the VADAS battery were important predictors of dementia at a 3-year period.
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| 8. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain
- 2010
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 20:4, s. 1039-1048
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Tidskriftsartikel (refereegranskat)abstract
- Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-derived molecules in cerebrospinal fluid (CSF) with chromogranin (Cg) derived peptides, representing the regulated secretion. Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50), and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP alpha), beta-cleaved soluble A beta PP (sA beta PP beta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes A beta PP into A beta, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. CSF Cg levels correlated to sA beta PP and A beta peptides in AD, MS, and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. These results suggest that a large part of A beta PP in the human central nervous system is processed in the regulated secretory pathway of neurons.
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| 9. |
- 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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| 10. |
- 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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