| 1. |
- Wiig, E H, et al.
(författare)
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The stability of AQT processing speed, ADAS-Cog and MMSE during acetylcholinesterase inhibitor treatment in Alzheimer's disease
- 2010
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 121:3, s. 186-193
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To explore the longitudinal stability of measures of cognition during treatment with acetylcholinesterase inhibitors (AchEI) in patients with Alzheimer's disease (AD). MATERIALS AND METHODS: Cognitive status was measured in a cohort of 60 patients at 6 months after initiation of treatment with AchEI (baseline) and after an additional 6 months of treatment (endpoint). A Quick Test of Cognitive Speed (AQT), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and MMSE were administered concurrently. RESULTS: Correlations (rho) between age and AQT processing speed were non-significant, but were significant for ADAS-Cog and Mini Mental State Examination (MMSE). AQT and ADAS-Cog means did not differ significantly between baseline and endpoint. There was a small, significant reduction in MMSE point scores. Measures of stability (Spearman's rho) were moderate-to-high for all tests. Means for subgroups did not differ as a function of medication type. CONCLUSIONS: AQT processing speed, ADAS-Cog, and MMSE measures proved stable during the second 6 months of treatment with AChEI.
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| 2. |
- Blennow, K., et al.
(författare)
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EVOLUTION OF A beta 42 AND A beta 40 LEVELS AND A beta 42/A beta 40 RATIO IN PLASMA DURING PROGRESSION OF ALZHEIMER'S DISEASE: A MULTICENTER ASSESSMENT
- 2009
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Ingår i: Journal Of Nutrition Health & Aging. - 1279-7707. ; 13:3, s. 205-208
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Konferensbidrag (refereegranskat)abstract
- Objective: To better understand the seemingly contradictory plasma beta-amyloid (A beta) results in Alzheimer's disease (AD) patients by using a newly developed plasma A beta assay, the INNO-BIA plasma A beta forms, in a multicenter study. Methods: A combined retrospective analysis of plasma A beta isoforms on mild cognitive impairment (MCI) from three large cross-sectional studies involving 643 samples from the participating German and Swedish centers. Results: Detection modules based on two different amino (N)-terminal specific A beta monoclonal antibodies demonstrated that A beta in plasma could be reliable quantified using a sandwich immunoassay technology with high precision, even for low A beta 42 plasma concentrations. A beta 40 and A beta 42 concentrations varied consistently with the ApoE genotype, while the A beta 42/A beta 40 ratio did not. Irrespective of the decrease of the A beta 42/A beta 40 ratio with age and MMSE, this parameter was strongly associated with AD, as defined in this study by elevated hyperphosphorylated (P-tau181P) levels in cerebrospinal fluid (CSF). Conclusion: A highly robust assay for repeatedly measuring A beta forms in plasma such as INNO-BIA plasma A beta forms might be a useful tool in a future risk assessment of AD.
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| 6. |
- Duits, Flora H., et al.
(författare)
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The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?
- 2014
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 10:6, s. 713-723
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimers disease (AD). Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/A beta(42) ratio and 0.08 for the p-tau/A beta(42) ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of greater than0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.
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| 7. |
- Eratne, D., et al.
(författare)
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Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders
- 2023
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Ingår i: Australian and New Zealand Journal of Psychiatry. - 0004-8674. ; 58:1, s. 70-81
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. Methods: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). Results: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. Conclusions: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.
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| 8. |
- Johansson, A, et al.
(författare)
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Increased frequency of a new polymorphism in the cycle 2 (cdc2) gene in patients with Alzheimer's disease frontotemporal dementia
- 2003
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Ingår i: Neuroscience Letters. - 0304-3940. ; 340:1, s. 69-73
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies show linkage between Alzheimer's disease (AD) and two loci on chromosome 10. The cell division cycle 2 (cdc2) gene is located close to one of the chromosome 10 markers, and is a candidate gene for AD since it is involved in the pathogenesis of AD. We sequenced coding exons and flanking intronic sequences and the promoter region on the cdc2 gene and found three new single nucleotide polymorphisms (SNPs). We analyzed 272 Caucasian AD cases, 160 controls and 70 cases with frontotemporal dementia (FTD) for these SNPs. Homozygosity for one of the SNPs (Ex6 + 7I/D) was more frequent in both AD and FTD cases than in controls. In the combined tauopathy (AD and FTD) group the odds ratio (OR) was 1.77 (95% CI 1.19-2.63) for the Ex6 + 7II genotype. Our findings suggest that the Ex6 + 7I allele is associated with tauopathies, both AD and FrD. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
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| 9. |
- Lagebrant, Alice, et al.
(författare)
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Brain injury markers in blood associate with generalised oedema on computed tomography after cardiac arrest
- 2021
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Ingår i: - : Springer Science and Business Media LLC. ; , s. 203-204
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Konferensbidrag (refereegranskat)abstract
- Introduction. According to the 2021 ERC/ESICM guideline recommen-dations, elevated neuron-specific enolase [NSE] levels as well as diffuseand extensive anoxic damage on neuroimaging are predictors of poorneurological outcome after cardiac arrest.(1) We previously describedthat NSE is elevated in patients with generalised oedema on com-puted tomography [CT]. (2).Objectives. In this study, we aim to examine the novel brain injurymarkers serum neurofilament light [NFL], glial fibrillary acidic protein[GFAP] and total-tau [tau] to predict the presence of generalised brainoedema.Methods. Retrospective analysis of patients examined with CT onclinical indication within the Target Temperature Management afterout-of-hospital cardiac arrest [TTM] trial. (2,3) Serum samples fromthe biobank sub study were prospectively collected at 48 h post arrestand analysed after trial completion as published. (4–7) The neuronalmarker NSE, the neuroaxonal injury markers NFL and tau and theastrocytic injury marker GFAP were correlated with the presence ofgeneralised oedema on CT, assessed by local radiologists through vis-ual evaluation. The prognostic accuracy of NSE ≥ 60 ug/l for predictinggeneralised oedema was also analysed.Results. 192 patients had data available on all four biomarkers at 48 hand were examined with CT < 168 h post arrest. Brain injury markerswere significantly higher in patients with generalised oedema as com-pared to patients without oedema on CT scans performed 24–168 hafter ROSC (p < 0.001) (Fig. 1A–D). For CT scans performed < 24 h, onlyNSE levels showed a significant correlation (p < 0.05). Biomarkers pre -dicted generalised oedema with area under the receiver operatingcharacteristics curve [AUC] 67.5–73.2% for CT scans performed < 24 h(n = 111), with no statistically significant difference between themarkers ( Fig. 2A). For scans performed 24–168 h (n = 81) AUC for pre -dicting generalised oedema was 78.1%-82.9%, with no statisticallysignificant difference between the markers. NSE ≥ 60 ug/l at 48 h, asrecommended by guidelines, predicted generalised oedema with 81%(95%CI 67–90%) sensitivity and 77% (95%CI 62–87%) specificity.Conclusion. Concentrations of all evaluated brain injury markerswere significantly higher in patients with generalised oedema on CTperformed after the first 24 h post arrest. Biomarker concentrationsindicate whether generalised oedema on CT is likely and may thus beclinically useful for deciding if a CT scan is sufficient for prognostica-tion or if a MRI is more appropriate.
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