Your search for: 'author:("Barkhof, Frederik")' has returned 22 results. (0.027s) Save search

Authors: Brueggen, Katharina | Dyrba, Martin | Barkhof, Frederik | Hausner, Lucrezia | Filippi, Massimo | Nestor, Peter J. | Hauenstein, Karlheinz | Klöppel, Stefan | Grothe, Michel J. | Kasper, Elisabeth | Teipel, Stefan J. | and the EDSD study group

Article Type: Research Article

Abstract: Background: Hippocampal grey matter (GM) atrophy predicts conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Pilot data suggests that mean diffusivity (MD) in the hippocampus, as measured with diffusion tensor imaging (DTI), may be a more accurate predictor of conversion than hippocampus volume. In addition, previous studies suggest that volume of the cholinergic basal forebrain may reach a diagnostic accuracy superior to hippocampal volume in MCI. Objective: The present study investigated whether increased MD and decreased volume of the hippocampus, the basal forebrain and other AD-typical regions predicted time to conversion from MCI to AD dementia. Methods: 79 …MCI patients with DTI and T1 -weighted magnetic resonance imaging (MRI) were retrospectively included from the European DTI Study in Dementia (EDSD) dataset. Of these participants, 35 converted to AD dementia after 6–46 months (mean: 21 months). We used Cox regression to estimate the relative conversion risk predicted by MD values and GM volumes, controlling for age, gender, education and center. Results: Decreased GM volume in all investigated regions predicted an increased risk for conversion. Additionally, increased MD in the right basal forebrain predicted increased conversion risk. Reduced volume of the right hippocampus was the only significant predictor in a stepwise model combining all predictor variables. Conclusion: Volume reduction of the hippocampus, the basal forebrain and other AD-related regions was predictive of increased risk for conversion from MCI to AD. In this study, volume was superior to MD in predicting conversion. Show more

Keywords: Diffusion tensor imaging, magnetic resonance imaging, Mild Cognitive Impairment, Alzheimer’s disease, atrophy, basal forebrain, cholinergic, early diagnosis

DOI: 10.3233/JAD-150063

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 197-204, 2015

Authors: van der Flier, Wiesje M. | Pijnenburg, Yolande A.L. | Prins, Niels | Lemstra, Afina W. | Bouwman, Femke H. | Teunissen, Charlotte E. | van Berckel, Bart N.M. | Stam, Cornelis J. | Barkhof, Frederik | Visser, Pieter Jelle | van Egmond, Evan | Scheltens, Philip

Article Type: Research Article

Abstract: Since its opening in 2000, patient care and research go hand in hand at the Alzheimer center of the VU University Medical Center, both organized in such a way that they mutually strengthen each other. Our mission is to give patients a voice by lifting the stigma on dementia, to find new diagnostic and treatment strategies, and, ultimately, to cure diseases that cause dementia. Our healthcare pathway is uniquely designed to accommodate all necessary investigations for the diagnostic work-up of dementia in one day (one-stop shop). A second unique feature is that research has been fully integrated in the healthcare …pathway. The resulting Amsterdam Dementia Cohort now includes over 4000 patients, and for the majority of these, we have MRI, EEG, blood (serum, plasma), DNA, and CSF available. The Amsterdam Dementia Cohort forms the basis of much of our research, which focuses on four major research lines: 1) variability in manifestation, 2) early diagnosis, 3) vascular factors, and 4) interventions. By answering research questions closely related to clinical practice, the results of our research can be looped back to improve clinical work-up for our patients. Show more

Keywords: Alzheimer's disease, dementia, diagnosis, investigations, mild cognitive impairment, work-up

DOI: 10.3233/JAD-132306

Citation: Journal of Alzheimer's Disease, vol. 41, no. 1, pp. 313-327, 2014

Authors: Vijverberg, Everard G.B. | Wattjes, Mike P. | Dols, Annemiek | Krudop, Welmoed A. | Möller, Christiane | Peters, Anne | Kerssens, Cora J. | Gossink, Flora | Prins, Niels D. | Stek, Max L. | Scheltens, Philip | van Berckel, Bart N.M. | Barkhof, Frederik | Pijnenburg, Yolande A.L.

Article Type: Research Article

Abstract: Background: Neuroimaging has a reasonable accuracy to differentiate behavioral variant frontotemporal dementia (bvFTD) from other neurodegenerative disorders, its value for the differentiation of bvFTD among subjects with acquired behavioral disturbances is unknown. Objective: To determine the diagnostic accuracy of MRI, additional [18 F]FDG-PET, and their combination for bvFTD among subjects with late onset behavioral changes. Methods: Patients with late onset behavioral changes referred to a memory clinic or psychiatric services were included. At baseline, 111 patients had a brain MRI scan and 74 patients received an additional [18 F]FDG-PET when the MRI was inconclusive. The consensus diagnosis after two-year-follow-up was …used as the gold standard to calculate sensitivity and specificity for baseline neuroimaging. Results: 27 patients had probable/definite bvFTD and 84 patients had a non-bvFTD diagnosis (primary psychiatric diagnosis or other neurological disorders). MRI had a sensitivity of 70% (95% CI 52–85%) with a specificity of 93% (95% CI 86–97%). Additional [18 F]FDG-PET had a sensitivity of 90% (95% CI 66–100%) with a specificity of 68% (95% CI 56–79%). The sensitivity of combined neuroimaging was 96% (95% CI 85–100%) with a specificity of 73% (95% CI 63–81%). In 66% of the genetic FTD cases, MRI lacked typical frontotemporal atrophy. 40% of cases with a false positive [18 F]FDG-PET scan had a primary psychiatric diagnosis. Conclusion: A good diagnostic accuracy was found for MRI and additional [18 F]FDG-PET for bvFTD in patients with late onset behavioral changes. Caution with the interpretation of neuroimaging results should especially be taken in cases with a genetic background and in cases with a primary psychiatric differential diagnosis where [18 F]FDG-PET is the only abnormal investigation. Show more

Keywords: Behavior, diagnostic accuracy, frontotemporal dementia, MRI, neuropsychology, psychiatric disorders

DOI: 10.3233/JAD-160285

Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1287-1297, 2016

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: Freeze, Whitney M. | Jacobs, Heidi I. L. | Gronenschild, Ed H. | Jansen, Jacobus F. A. | Burgmans, Saartje | Aalten, Pauline | Clerx, Lies | Vos, Stephanie J. | van Buchem, Mark A. | Barkhof, Frederik | van der Flier, Wiesje M. | Verbeek, Marcel M. | Rikkert, Marcel Olde | Backes, Walter H. | Verhey, Frans R. | on behalf of the LeARN project

Article Type: Research Article

Abstract: Cerebral small vessel disease (cSVD) and amyloid-β (Aβ) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Aβ have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer’s disease (AD) (n  = 24), mild cognitive impairment (MCI) (n  = 26), and subjective cognitive complaints (SCC) (n  = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. Aβ pathology was assessed as cerebrospinal fluid-derived Aβ1 - 42 levels and dichotomized into normal …or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and Aβ on HV in the total participant group (n  = 87) and in the non-demented group (including SCC and MCI individuals only, n  = 63). The results revealed that abnormal Aβ and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, Aβ and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF Aβ42 levels, but not in individuals with normal CSF Aβ42 levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal Aβ levels are at an increased risk of accelerated disease progression when concomitant cSVD is present. Show more

Keywords: Amyloid-beta, cerebral small vessel disease, dementia, neurodegeneration

DOI: 10.3233/JAD-160474

Citation: Journal of Alzheimer's Disease, vol. 55, no. 1, pp. 333-342, 2017

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: Louwersheimer, Eva | Cohn-Hokke, Petra E. | Pijnenburg, Yolande A.L. | Weiss, Marjan M. | Sistermans, Erik A. | Rozemuller, Annemieke J. | Hulsman, Marc | van Swieten, John C. | van Duijn, Cock M. | Barkhof, Frederik | Koene, Teddy | Scheltens, Philip | Van der Flier, Wiesje M. | Holstege, Henne

Article Type: Research Article

Abstract: Background: The major genetic risk factor for late onset Alzheimer’s disease (AD) is the APOE -ɛ 4 allele. However, APOE -ɛ 4 homozygosity is not fully penetrant, suggesting co-occurrence of additional genetic variants. Objective: To identify genetic factors that, next to APOE -ɛ 4 homozygosity, contribute to the development of AD. Methods: We identified a family with nine AD patients spanning four generations, with an inheritance pattern suggestive of autosomal dominant AD, with no variants in PSEN1 , PSEN2 , or APP . We collected DNA from four affected and seven unaffected family members and performed exome sequencing on DNA …from three affected and one unaffected family members. Results: All affected family members were homozygous for the APOE -ɛ 4 allele. Statistical analysis revealed that AD onset in this family was significantly earlier than could be expected based on APOE genotype and gender. Next to APOE -ɛ 4 homozygosity, we found that all four affected family members carried a rare variant in the VPS10 domain of the SORL1 gene, associated with AβPP processing and AD risk. Furthermore, three of four affected family members carried a rare variant in the TSHZ3 gene, also associated with AβPP processing. Affected family members presented between 61 and 74 years, with variable presence of microbleeds/cerebral amyloid angiopathy and electroencephalographic abnormalities. Conclusion: We hypothesize that next to APOE -ɛ 4 homozygosity, impaired SORL1 protein function, and possibly impaired TSHZ3 function, further disturbed Aβ processing. The convergence of these genetic factors over several generations might clarify the increased AD penetrance and the autosomal dominant-like inheritance pattern of AD as observed in this family. Show more

Keywords: Alzheimer’s disease, APOE, genetics, penetrance, SORL1

DOI: 10.3233/JAD-160091

Citation: Journal of Alzheimer's Disease, vol. 56, no. 1, pp. 63-74, 2017

Authors: Hafkemeijer, Anne | Möller, Christiane | Dopper, Elise G.P. | Jiskoot, Lize C. | van den Berg-Huysmans, Annette A. | van Swieten, John C. | van der Flier, Wiesje M. | Vrenken, Hugo | Pijnenburg, Yolande A.L. | Barkhof, Frederik | Scheltens, Philip | van der Grond, Jeroen | Rombouts, Serge A.R.B.

Article Type: Research Article

Abstract: Background/Objective: Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. We applied longitudinal resting state functional magnetic resonance imaging (fMRI) to delineate functional brain connections relevant for disease progression and diagnostic accuracy. Methods: We used two-center resting state fMRI data of 20 AD patients (65.1±8.0 years), 12 bvFTD patients (64.7±5.4 years), and 22 control subjects (63.8±5.0 years) at baseline and 1.8-year follow-up. We used whole-network and voxel-based network-to-region analyses to study group differences in functional connectivity at baseline and follow-up, and longitudinal changes in connectivity within and between groups. Results: At baseline, …connectivity between paracingulate gyrus and executive control network, between cuneal cortex and medial visual network, and between paracingulate gyrus and salience network was higher in AD compared with controls. These differences were also present after 1.8 years. At follow-up, connectivity between angular gyrus and right frontoparietal network, and between paracingulate gyrus and default mode network was lower in bvFTD compared with controls, and lower compared with AD between anterior cingulate gyrus and executive control network, and between lateral occipital cortex and medial visual network. Over time, connectivity decreased in AD between precuneus and right frontoparietal network and in bvFTD between inferior frontal gyrus and left frontoparietal network. Longitudinal changes in connectivity between supramarginal gyrus and right frontoparietal network differ between both patient groups and controls. Conclusion: We found disease-specific brain regions with longitudinal connectivity changes. This suggests the potential of longitudinal resting state fMRI to delineate regions relevant for disease progression and for diagnostic accuracy, although no group differences in longitudinal changes in the direct comparison of AD and bvFTD were found. Show more

Keywords: Alzheimer’s disease, frontotemporal dementia, frontotemporal lobar degeneration, functional connectivity, longitudinal, resting state fMRI, resting state networks

DOI: 10.3233/JAD-150695

Citation: Journal of Alzheimer's Disease, vol. 55, no. 2, pp. 521-537, 2017