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- De Kort, A. M., et al.
(författare)
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Decreased Cerebrospinal Fluid Amyloid beta 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy
- 2023
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Ingår i: Annals of neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 93:6, s. 1173-86
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vascular amyloid beta (A beta) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker of CAA. We studied the diagnostic potential of the peptides A beta 38, A beta 40, A beta 42, and A beta 43 in patients with sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD).Methods: A beta peptides were quantified by immunoassays in a discovery group (26 patients with sCAA and 40 controls), a validation group (40 patients with sCAA, 40 patients with AD, and 37 controls), and a group of 22 patients with D-CAA and 54 controls. To determine the diagnostic accuracy, the area under the curve (AUC) was calculated using a receiver operating characteristic curve with 95% confidence interval (CI).Results: We found decreased levels of all A beta peptides in sCAA patients and D-CAA patients compared to controls. The difference was most prominent for A beta 42 (AUC of sCAA vs controls for discovery: 0.90, 95% CI = 0.82-0.99; for validation: 0.94, 95% CI = 0.89-0.99) and A beta 43 (AUC of sCAA vs controls for discovery: 0.95, 95% CI = 0.88-1.00; for validation: 0.91, 95% CI = 0.83-1.0). All A beta peptides except A beta 43 were also decreased in sCAA compared to AD (CSF A beta 38: AUC = 0.82, 95% CI = 0.71-0.93; CSF A beta 40: AUC = 0.88, 95% CI = 0.80-0.96; CSF A beta 42: AUC = 0.79, 95% CI = 0.66-0.92).Interpretation: A combined biomarker panel of CSF A beta 38, A beta 40, A beta 42, and A beta 43 has potential to differentiate sCAA from AD and controls, and D-CAA from controls. ANN NEUROL 2023
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- Albers, J.M.C., et al.
(författare)
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Treatment strategy, disease activity, and outcome in four cohorts of patients with early rheumatoid arthritis
- 2001
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 60:5, s. 453-458
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Tidskriftsartikel (refereegranskat)abstract
- Objective-To compare four different inception cohorts of patients with early rheumatoid arthritis (RA) with respect to treatment strategies, disease activity, and outcome during a five year follow up period. Method-Data from cohorts of patients with early RA, with a standardised assessment at least every six months for five years from four different centres, were included in one database. Owing to slight differences in the individual study designs, linearly interpolated values were calculated to complete the standard follow up schedule. Results-Despite similar inclusion criteria, significant differences in demographic factors and baseline disease activity were found between the different cohorts. During the follow up an aggressive treatment strategy was followed in the Dutch and Finnish cohort, an intermediate strategy in the British cohort, and a conservative strategy in the Swedish cohort. A significant improvement in disease activity was seen in all cohorts, though the most rapid and striking improvement was seen in those receiving aggressive treatment. This resulted in less radiographic destruction in the long run. Conclusion-This observational study of cohorts of patients with early RA confirms that early aggressive treatment results not only in a more rapid reduction of disease activity but also in less radiographic progression in the long term.
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- van den Berg, E., et al.
(författare)
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Cerebrospinal Fluid Panel of Synaptic Proteins in Cerebral Amyloid Angiopathy and Alzheimer's Disease
- 2023
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 92:2, s. 467-475
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) share pathogenic pathways related to amyloid-beta deposition. Whereas AD is known to affect synaptic function, such an association for CAA remains yet unknown. Objective: We therefore aimed to investigate synaptic dysfunction in CAA. Methods: Multiple reaction monitoring mass spectrometry was used to quantify cerebrospinal fluid (CSF) concentrations of 15 synaptic proteins in CAA and AD patients, and age- and sex-matched cognitively unimpaired controls. Results: We included 25 patients with CAA, 49 patients with AD, and 25 controls. Only neuronal pentraxin-2 levels were decreased in the CSF of CAA patients compared with controls (p = 0.04). CSF concentrations of 12 other synaptic proteins were all increased in AD compared with CAA or controls (all p= 0.01) and were unchanged between CAA and controls. Synaptic protein concentrations in the subgroup ofCAApatients positive forADbiomarkers (CAA/ATN+; n = 6) were similar to AD patients, while levels in CAA/ATN- (n = 19) were comparable with those in controls. A regression model including all synaptic proteins differentiated CAA from AD at high accuracy levels (area under the curve 0.987). Conclusion: In contrast to AD, synaptic CSF biomarkers were found to be largely unchanged in CAA. Moreover, concomitant AD pathology in CAA is associated with abnormal synaptic protein levels. Impaired synaptic function in AD was confirmed in this independent cohort. Our findings support an apparent differential involvement of synaptic dysfunction in CAA and AD and may reflect distinct pathological mechanisms.
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- van den Berg, Emma, et al.
(författare)
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Profiling amyloid-β peptides as biomarkers for cerebral amyloid angiopathy
- 2024
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Ingår i: JOURNAL OF NEUROCHEMISTRY. - 0022-3042 .- 1471-4159.
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Tidskriftsartikel (refereegranskat)abstract
- Brain amyloid-beta (A beta) deposits are key pathological hallmarks of both cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Microvascular deposits in CAA mainly consist of the A beta(40) peptide, whereas A beta(42) is the predominant variant in parenchymal plaques in AD. The relevance in pathogenesis and diagnostic accuracy of various other A beta isoforms in CAA remain understudied. We aimed to investigate the biomarker potential of various A beta isoforms in cerebrospinal fluid (CSF) to differentiate CAA from AD pathology. We included 25 patients with probable CAA, 50 subjects with a CSF profile indicative of AD pathology (AD-like), and 23 age- and sex-matched controls. CSF levels of A beta(1-34), A beta(1-37), A beta(1-38), A beta(1-39), A beta(1-40), and A beta(1-42) were quantified by liquid chromatography mass spectrometry. Lower CSF levels of all six A beta peptides were observed in CAA patients compared with controls (p = 0.0005-0.03). Except for A beta(1-42) (p = 1.0), all peptides were decreased in CAA compared with AD-like subjects (p = 0.007-0.03). Besides A beta(1-42), none of the A beta peptides were decreased in AD-like subjects compared with controls. All A beta peptides combined differentiated CAA from AD-like subjects better (area under the curve [AUC] 0.84) than individual peptide levels (AUC 0.51-0.75). Without A beta(1-42) in the model (since decreased A beta(1-42) served as AD-like selection criterion), the AUC was 0.78 for distinguishing CAA from AD-like subjects. CAA patients and AD-like subjects showed distinct disease-specific CSF A beta profiles. Peptides shorter than A beta(1-42) were decreased in CAA patients, but not AD-like subjects, which could suggest different pathological mechanisms between vascular and parenchymal A beta accumulation. This study supports the potential use of this panel of CSF A beta peptides to indicate presence of CAA pathology with high accuracy.
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- Ekker, Merel, et al.
(författare)
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Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis.
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients.The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.
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- Kamorowski, Jennifer, et al.
(författare)
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Forensic Mental Health Practitioners' Use of Structured Risk Assessment Instruments, Views about Bias in Risk Evaluations, and Strategies to Counteract It
- 2022
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Ingår i: International Journal of Forensic Mental Health. - : Informa UK Limited. - 1499-9013 .- 1932-9903. ; 21:1, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- The use of structured risk assessment instruments (SRAIs) has increased significantly over the past decades, with research documenting variation between countries. The use of SRAIs, their perceived utility and potential for mitigating bias in forensic risk evaluations (FREs) was investigated in a survey of Dutch forensic mental health practitioners (N = 110) We found generally positive views regarding SRAI utility. Bias in FREs was of concern to respondents. We found no evidence of a bias blind spot (the belief that oneself is less prone to bias than peers/colleagues). SRAIs were rated as the most effective debiasing strategy, but respondents also endorsed introspection. There were few differences in beliefs about sources of bias or debiasing strategies between respondents who had bias training and those who had not, suggesting the need for development of effective strategies to mitigate bias and training related to bias in FREs.
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- Kamorowski, Jennifer, et al.
(författare)
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'He seems odd': the effects of risk-irrelevant information and actuarial risk estimates on mock jurors' perceptions of sexual recidivism risk
- 2022
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Ingår i: Psychology Crime & Law. - : Informa UK Limited. - 1068-316X .- 1477-2744. ; 28:4
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has shown that mock and actual jurors give little weight to actuarial sexual offending recidivism risk estimates when making decisions regarding civil commitment for so-called sexually violent predators (SVPs). We hypothesized that non-risk related factors, such as irrelevant contextual information and jurors' information-processing style, would influence mock jurors' perceptions of sexual recidivism risk. This preregistered experimental study examined the effects of mock jurors' (N = 427) need for cognition (NFC), irrelevant contextual information in the form of the offender's social attractiveness, and an actuarial risk estimate on mock jurors' estimates of sexual recidivism risk related to a simulated SVP case vignette. Mock jurors exposed to negative risk-irrelevant characteristics of the offender estimated sexual recidivism risk as higher than mock jurors exposed to positive information about the offender. However, this effect was no longer significant after mock jurors had reviewed Static-99R actuarial risk estimate information. We found no support for the hypothesis that the level of NFC moderates the relationship between risk-irrelevant contextual information and risk estimates. Future research could explore additional individual characteristics or attitudes among mock jurors that may influence perceptions of sexual recidivism risk and insensitivity to actuarial risk estimates.
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