Your search for: 'author:("Barkhof, Frederik")' has returned 8 results. (0.02s) Save search

Authors: Groot, Colin | Tolboom, Nelleke | Ikonomovic, Milos D. | Lammertsma, Adriaan A. | Boon, Baayla D.C. | Barkhof, Frederik | Scheltens, Philip | Klunk, William E. | Rozemuller, Annemieke J.M. | Ossenkoppele, Rik | van Berckel, Bart N.M.

Article Type: Short Communication

Abstract: This single case study examines selective Pittsburgh compound-B (PiB) binding to an intracerebral light-chain amyloidoma using a 90-minute dynamic [11 C]PiB-PET scan and brain biopsy tissue. Parametric non-displaceable binding potential (BPND ) images showed low specific binding in the amyloidoma (BPND = 0.23), while relative tracer delivery was adequate (R1 = 0.44). Histology of the tissue revealed strong coloring with Congo-red, thioflavin-S, and X-34, indicating presence of amyloid. However, immunological staining with 6F/3D revealed absence of amyloid-β and histofluorescence of 6-CN-PiB, a highly fluorescent derivative of PiB, was at background levels. Our results suggest that PiB does not detect the …atypical amyloid pathology associated with an intracerebral light-chain amyloidoma. These findings are of interest to clinicians and researchers applying [11 C]PiB-PET to detect atypical forms of amyloid pathology. Show more

Keywords: Amyloid, case study, histology, positron emission tomography

DOI: 10.3233/JAD-180316

Citation: Journal of Alzheimer's Disease, vol. 65, no. 1, pp. 71-77, 2018

Authors: Reimand, Juhan | Groot, Colin | Teunissen, Charlotte E. | Windhorst, Albert D. | Boellaard, Ronald | Barkhof, Frederik | Nazarenko, Sergei | van der Flier, Wiesje M. | van Berckel, Bart N.M. | Scheltens, Philip | Ossenkoppele, Rik | Bouwman, Femke

Article Type: Research Article

Abstract: Background: Amyloid-β positron emission tomography (PET) and cerebrospinal fluid (CSF) Aβ42 are considered interchangeable for clinical diagnosis of Alzheimer’s disease. Objective: To explore the clinical reasoning for requesting additional amyloid-β PET after performing CSF biomarkers. Methods: We retrospectively identified 72 memory clinic patients who underwent amyloid-β PET after CSF biomarkers analysis for clinical diagnostic evaluation between 2011 and 2019. We performed patient chart reviews to identify factors which led to additional amyloid-β PET. Additionally, we assessed accordance with appropriate-use-criteria (AUC) for amyloid-β PET. Results: Mean patient age was 62.0 (SD = 8.1) and mean Mini-Mental State Exam score was 23.6 (SD = 3.8). CSF …analysis conflicting with the clinical diagnosis was the most frequent reason for requesting an amyloid-β PET scan (n  = 53, 74%), followed by incongruent MRI (n  = 16, 22%), unusual clinical presentation (n  = 11, 15%) and young age (n  = 8, 11%). An amyloid-β PET scan was rarely (n  = 5, 7%) requested in patients with a CSF Aβ+/tau+ status. Fifteen (47%) patients with a post-PET diagnosis of AD had a predominantly non-amnestic presentation. In n  = 11 (15%) cases, the reason that the clinician requested amyloid-β was not covered by AUC. This happened most often (n  = 7) when previous CSF analysis did not support current clinical diagnosis, which led to requesting amyloid-β PET. Conclusion: In this single-center study, the main reason for requesting an amyloid-β PET scan after performing CSF biomarkers was the occurrence of a mismatch between the primary clinical diagnosis and CSF Aβ/tau results. Show more

Keywords: Alzheimer’s disease, amyloid, cerebrospinal fluid, positron emission tomography, tau proteins

DOI: 10.3233/JAD-190836

Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 559-569, 2020

Authors: Boomsma, Jooske M.F. | Exalto, Lieza G. | Barkhof, Frederik | van den Berg, Esther | de Bresser, Jeroen | Heinen, Rutger | Leeuwis, Anna E. | Prins, Niels D. | Scheltens, Philip | Weinstein, Henry C. | van der Flier, Wiesje M. | Biessels, Geert Jan | behalf of the TRACE-VCI study group

Article Type: Research Article

Abstract: Background: Memory clinic patients frequently present with different forms of vascular brain injury due to different etiologies, often co-occurring with Alzheimer’s disease (AD) pathology. Objective: We studied how cognition was affected by different forms of vascular brain injury, possibly in interplay with AD pathology. Methods: We included 860 memory clinic patients with vascular brain injury on magnetic resonance imaging (MRI), receiving a standardized evaluation including cerebrospinal fluid (CSF) biomarker analyses (n  = 541). The cognitive profile of patients with different forms of vascular brain injury on MRI (moderate/severe white matter hyperintensities (WMH) (n  = 398), microbleeds (n  = 368), lacunar (n  = 188) and …non-lacunar (n  = 96) infarct(s), macrobleeds (n  = 16)) was assessed by: 1) comparison of all these different forms of vascular brain injury with a reference group (patients with only mild WMH (n  = 205) without other forms of vascular brain injury), using linear regression analyses also stratified for CSF biomarker AD profile and 2) multivariate linear regression analysis. Results: The cognitive profile was remarkably similar across groups. Compared to the reference group effect sizes on all domains were <0.2 with narrow 95% confidence intervals, except for non-lacunar infarcts on information processing speed (age, sex, and education adjusted mean difference from reference group (β: – 0.26, p  = 0.05). Results were similar in the presence (n  = 300) or absence (n  = 241) of biomarker co-occurring AD pathology. In multivariate linear regression analysis, higher WMH burden was related to a slightly worse performance on attention and executive functioning (β: – 0.08, p  = 0.02) and working memory (β: – 0.08, p  = 0.04). Conclusion: Although different forms of vascular brain injury have different etiologies and different patterns of cerebral damage, they show a largely similar cognitive profile in memory clinic patients regardless of co-occurring AD pathology. Show more

Keywords: Cerebral small vessel diseases, cerebrovascular disorders, cognitive disorders, neuropsychological test

DOI: 10.3233/JAD-180696

Citation: Journal of Alzheimer's Disease, vol. 68, no. 3, pp. 1273-1286, 2019

Authors: Groeneveld, Onno N. | Moneti, Costanza | Heinen, Rutger | de Bresser, Jeroen | Kuijf, Hugo J. | Exalto, Lieza G. | Boomsma, Jooske M.F. | Kappelle, L.Jaap | Barkhof, Frederik | Prins, Niels D. | Scheltens, Philip | van der Flier, Wiesje M. | Biessels, Geert Jan | and on behalf of the TRACE-VCI study group

Article Type: Research Article

Abstract: Background: Type 2 diabetes mellitus (T2DM) increases the risk of vascular cognitive impairment (VCI). It is unknown which type of vascular lesions and co-morbid etiologies, in particular Alzheimer’s disease pathology, are associated with T2DM in patients with VCI, and how this relates to cognition and prognosis. Objective: To compare brain MRI and cerebrospinal fluid (CSF) markers, cognition, and prognosis in patients with possible VCI with and without T2DM. Methods: We included 851 memory clinic patients with vascular brain injury on MRI (i.e., possible VCI) from a prospective cohort study (T2DM: n  = 147, 68.4±7.9 years, 63% men; no T2DM: n  = 704, …67.6±8.5 years, 52% men). At baseline, we assessed between-group differences in brain MRI abnormalities, CSF markers of Alzheimer’s disease, and cognitive profile. After two years follow-up, we compared occurrence of cognitive decline, stroke, and death. Results: The distribution of clinical diagnoses did not differ between patients with and without T2DM. T2DM patients had more pronounced brain atrophy (total and white matter volume), and more lacunar infarcts, whereas microbleeds were less common (all p  < 0.05). CSF amyloid-β levels were similar between the groups. T2DM patients performed worse on working memory (effect size: – 0.17, p  = 0.03) than those without, whereas performance on other domains was similar. During follow-up, risk of further cognitive decline was not increased in T2DM.∥Conclusion: In patients with possible VCI, presence of T2DM is related to more pronounced brain atrophy and a higher burden of lacunar infarcts, but T2DM does not have a major impact on cognitive profile or prognosis.∥ Show more

Keywords: Cerebrospinal fluid, magnetic resonance imaging, prognosis, type 2 diabetes mellitus, vascular brain injury

DOI: 10.3233/JAD-180914

Citation: Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 311-322, 2019

Authors: Bouts, Mark J.R.J. | Möller, Christiane | Hafkemeijer, Anne | van Swieten, John C. | Dopper, Elise | van der Flier, Wiesje M. | Vrenken, Hugo | Wink, Alle Meije | Pijnenburg, Yolande A.L. | Scheltens, Philip | Barkhof, Frederik | Schouten, Tijn. M. | de Vos, Frank | Feis, Rogier A. | van der Grond, Jeroen | de Rooij, Mark | Rombouts, Serge A.R.B.

Article Type: Research Article

Abstract: Background/Objective: Overlapping clinical symptoms often complicate differential diagnosis between patients with Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Magnetic resonance imaging (MRI) reveals disease specific structural and functional differences that aid in differentiating AD from bvFTD patients. However, the benefit of combining structural and functional connectivity measures to—on a subject-basis—differentiate these dementia-types is not yet known. Methods: Anatomical, diffusion tensor (DTI), and resting-state functional MRI (rs-fMRI) of 30 patients with early stage AD, 23 with bvFTD, and 35 control subjects were collected and used to calculate measures of structural and functional tissue status. All measures were used separately …or selectively combined as predictors for training an elastic net regression classifier. Each classifier’s ability to accurately distinguish dementia-types was quantified by calculating the area under the receiver operating characteristic curves (AUC). Results: Highest AUC values for AD and bvFTD discrimination were obtained when mean diffusivity, full correlations between rs-fMRI-derived independent components, and fractional anisotropy (FA) were combined (0.811). Similarly, combining gray matter density (GMD), FA, and rs-fMRI correlations resulted in highest AUC of 0.922 for control and bvFTD classifications. This, however, was not observed for control and AD differentiations. Classifications with GMD (0.940) and a GMD and DTI combination (0.941) resulted in similar AUC values (p  = 0.41). Conclusion: Combining functional and structural connectivity measures improve dementia-type differentiations and may contribute to more accurate and substantiated differential diagnosis of AD and bvFTD patients. Imaging protocols for differential diagnosis may benefit from also including DTI and rs-fMRI. Show more

Keywords: Alzheimer’s disease, behavioral variant frontotemporal dementia, classification, differential diagnosis, diffusion tensor imaging, functional MRI, machine learning

DOI: 10.3233/JAD-170893

Citation: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1827-1839, 2018

Authors: Ulugut Erkoyun, Hulya | van der Lee, Sven J. | Nijmeijer, Bas | van Spaendonk, Rosalina | Nelissen, Anne | Scarioni, Marta | Dijkstra, Anke | Samancı, Bedia | Gürvit, Hakan | Yıldırım, Zerrin | Tepgeç, Fatih | Bilgic, Basar | Barkhof, Frederik | Rozemuller, Annemieke | van der Flier, Wiesje M. | Scheltens, Philip | Cohn-Hokke, Petra | Pijnenburg, Yolande

Article Type: Research Article

Abstract: Background: Right temporal variant frontotemporal dementia (rtvFTD) has been generally considered as a right sided variant of semantic variant primary progressive aphasia (svPPA), which is a genetically sporadic disorder. Recently, we have shown that rtvFTD has a unique clinical syndrome compared to svPPA and behavioral variant frontotemporal dementia. Objective: We challenge the assumption that rtvFTD is a sporadic, non-familial variant of FTD by identifying potential autosomal dominant inheritance and related genes in rtvFTD. Methods: We collected all subjects with a diagnosis of FTD or primary progressive aphasia who had undergone genetic screening (n  = 284) and subsequently who had a genetic …variant (n  = 48) with a diagnosis of rtvFTD (n  = 6) in 2 specialized memory clinics. Results: Genetic variants in FTD related genes were found in 33% of genetically screened rtvFTD cases; including MAPT (n  = 4), GRN (n  = 1), and TARDBP (n  = 1) genes, whereas only one svPPA case had a genetic variant in our combined cohorts. Additionally, 4 out of 6 rtvFTD subjects had a strong family history for dementia. Conclusion: Our results demonstrate that rtvFTD, unlike svPPA, is not a pure sporadic, but a heterogeneous potential genetic variant of FTD, and screening for genetic causes for FTD should be performed in patients with rtvFTD. Show more

Keywords: Dementia, frontotemporal dementia, frontotemporal lobar degeneration, genetic, GRN, MAPT, right temporallobe, TARDBP

DOI: 10.3233/JAD-201191

Citation: Journal of Alzheimer's Disease, vol. 79, no. 3, pp. 1195-1201, 2021

Authors: Westwood, Sarah | Baird, Alison L. | Anand, Sneha N. | Nevado-Holgado, Alejo J. | Kormilitzin, Andrey | Shi, Liu | Hye, Abdul | Ashton, Nicholas J. | Morgan, Angharad R. | Bos, Isabelle | Vos, Stephanie J.B. | Baker, Susan | Buckley, Noel J. | Ten Kate, Mara | Scheltens, Philip | Teunissen, Charlotte E. | Vandenberghe, Rik | Gabel, Silvy | Meersmans, Karen | Engelborghs, Sebastiaan | De Roeck, Ellen E. | Sleegers, Kristel | Frisoni, Giovanni B. | Blin, Olivier | Richardson, Jill C. | Bordet, Régis | Molinuevo, José L. | Rami, Lorena | Wallin, Anders | Kettunen, Petronella | Tsolaki, Magda | Verhey, Frans | Lléo, Alberto | Sala, Isabel | Popp, Julius | Peyratout, Gwendoline | Martinez-Lage, Pablo | Tainta, Mikel | Johannsen, Peter | Freund-Levi, Yvonne | Frölich, Lutz | Dobricic, Valerija | Legido-Quigley, Cristina | Bertram, Lars | Barkhof, Frederik | Zetterberg, Henrik | Morgan, B. Paul | Streffer, Johannes | Visser, Pieter Jelle | Lovestone, Simon

Article Type: Research Article

Abstract: We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer’s disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. …Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ɛ 4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure. Show more

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, plasma, proteomics

DOI: 10.3233/JAD-190434

Citation: Journal of Alzheimer's Disease, vol. 74, no. 1, pp. 213-225, 2020

Authors: Shi, Liu | Winchester, Laura M. | Liu, Benjamine Y. | Killick, Richard | Ribe, Elena M. | Westwood, Sarah | Baird, Alison L. | Buckley, Noel J. | Hong, Shengjun | Dobricic, Valerija | Kilpert, Fabian | Franke, Andre | Kiddle, Steven | Sattlecker, Martina | Dobson, Richard | Cuadrado, Antonio | Hye, Abdul | Ashton, Nicholas J. | Morgan, Angharad R. | Bos, Isabelle | Vos, Stephanie J.B. | ten Kate, Mara | Scheltens, Philip | Vandenberghe, Rik | Gabel, Silvy | Meersmans, Karen | Engelborghs, Sebastiaan | De Roeck, Ellen E. | Sleegers, Kristel | Frisoni, Giovanni B. | Blin, Olivier | Richardson, Jill C. | Bordet, Régis | Molinuevo, José L. | Rami, Lorena | Wallin, Anders | Kettunen, Petronella | Tsolaki, Magda | Verhey, Frans | Lleó, Alberto | Alcolea, Daniel | Popp, Julius | Peyratout, Gwendoline | Martinez-Lage, Pablo | Tainta, Mikel | Johannsen, Peter | Teunissen, Charlotte E. | Freund-Levi, Yvonne | Frölich, Lutz | Legido-Quigley, Cristina | Barkhof, Frederik | Blennow, Kaj | Rasmussen, Katrine Laura | Nordestgaard, Børge Grønne | Frikke-Schmidt, Ruth | Nielsen, Sune Fallgaard | Soininen, Hilkka | Vellas, Bruno | Kloszewska, Iwona | Mecocci, Patrizia | Zetterberg, Henrik | Morgan, B. Paul | Streffer, Johannes | Visser, Pieter Jelle | Bertram, Lars | Nevado-Holgado, Alejo J. | Lovestone, Simon

Article Type: Research Article

Abstract: Background: Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer’s disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown. Objective: We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes. Methods: We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature …induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677). Results: We identified a 100-protein signature induced by DKK1 in vitro . Subsets of proteins, along with age and apolipoprotein E ɛ 4 genotype distinguished amyloid pathology (A + T–N–, A+T+N–, A+T–N+, and A+T+N+) from no AD pathology (A–T–N–) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts. Conclusions: Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo . Show more

Keywords: ATN framework, Dickkopf-1, replication, SomaScan, Wnt signaling

DOI: 10.3233/JAD-200208

Citation: Journal of Alzheimer's Disease, vol. 77, no. 3, pp. 1353-1368, 2020