Your search for: 'author:("Pijnenburg, Yolande")' has returned 27 results. (0.021s) Save search

Authors: Staekenborg, Salka S. | Pijnenburg, Yolande A.L. | Lemstra, Afina W. | Scheltens, Philip | vd Flier, Wiesje M.

Article Type: Research Article

Abstract: Background: Dementia is typically known for its insidious onset and slowly progressive course, but a subgroup deteriorates fast and dies within years or even months. Objective: The purpose of this study was to characterize dementia patients with a rapidly progressive course to death and evaluate their cause of death. Methods: We retrospectively included all patients from the Amsterdam Dementia Cohort who died within two years after diagnosis. We evaluated the characteristics of these rapid progressors and compared them to patients known to be alive two years after diagnosis (‘non-rapid mortality’). Results: We included 129 dementia patients (13% of our total …cohort with known follow-up) with rapid mortality (age 72±10 y [29%  <65 y], 70[55%]M, MMSE 20±5). Mean(SD) survival was 12±7 months. Compared to non-rapid mortality patients (n  = 892; age 68±9, 503(56%)M, MMSE 22±5), patients with rapid mortality were slightly older at time of diagnosis, had lower MMSE scores, more depressive symptoms and higher prevalence of a cardiovascular history (all p  < 0.05). Alzheimer’s disease (AD, 43%) was most frequent in patients with rapid mortality, but the occurrence was much lower compared to non-rapid mortality patients (71%), while all other dementia diagnoses, especially Creutzfeldt-Jakob disease (CJD), vascular dementia (VaD), and frontotemporal dementia (FTD), were more frequent (p  < 0.001). There were no specific characteristics for AD patients with rapid versus non-rapid mortality, especially APOE genotypes and CSF-profiles were comparable (p  > 0.70). Cause of death was highly variable without a clear relation to dementia diagnosis, with exception of dementia itself in CJD, intracerebral hematoma in VaD, and motor neuron disease in FTD. Conclusions: Short survival is relatively common (∼13% in our cohort) and occurs in all different types of dementia, with overrepresentation of non-AD dementias like CJD, VaD, and FTD. Show more

Keywords: Dementia, mortality, rapid progression

DOI: 10.3233/JAD-151063

Citation: Journal of Alzheimer's Disease, vol. 53, no. 1, pp. 135-142, 2016

Authors: Verwey, Nicolaas A. | Teunissen, Charlotte E. | Hoozemans, Jeroen J.M. | Rozemuller, Annemieke J.M. | Scheltens, Philip | Pijnenburg, Yolande A.L.

Article Type: Short Communication

Abstract: To investigate amyloid-β (Aβ) in frontotemporal dementia (FTD), cerebrospinal fluid (CSF) Aβ38 , Aβ40 , and Aβ42 in frontotemporal lobar degeneration (FTLD; N = 18 genetically and/or pathologically confirmed and N = 8 FTD with concomitant amyotrophic lateral sclerosis) were compared with Alzheimer’s disease (AD; pathological or Pittsburgh-compound-B Positron-emission-tomography (PIB-PET) positive; N = 25) and controls (N = 24). For all the Aβ subtypes, group difference was seen and post-hoc analysis revealed lower levels in FTLD compared to controls (p ≤0.05). Aβ42/40 ratio showed no difference between FTLD and controls; however, a difference was seen between AD versus FTLD (p  < 0.01). This is an intriguing finding, suggesting a …possible role of Aβ in FTLD pathogenesis. Show more

Keywords: Alzheimer’s disease, amyloid, frontotemporal dementia, frontotemporal lobar degeneration

DOI: 10.3233/JAD-190344

Citation: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 15-20, 2019

Authors: Gerritsen, Adrie A.J. | Bakker, Christian | Verhey, Frans R.J. | Bor, Hans | Pijnenburg, Yolande A.L. | de Vugt, Marjolein E. | Koopmans, Raymond T.C.M.

Article Type: Research Article

Abstract: Background: The progression of dementia in people with young-onset dementia (YOD) is relatively unknown. Objective: To investigate the progression of dementia and cognitive decline in the three most common subtypes in YOD and to explore which factors are associated with this course. Methods: The course of dementia was examined in 198 people with YOD. The primary outcomes were cognitive function, as assessed by the Mini-Mental State Examination (MMSE) and dementia severity, as assessed by the Global Deterioration Scale (GDS). Mixed-model analyses were used to explore factors associated with the course of dementia of the diagnostic sub-types. Results: The mean overall …two-year progression of dementia severity was 0.9 GDS points, this was a statistically significant change (p  = 0.012) and was not significantly different for the three dementia subtypes. The mean overall two-year decline in cognitive function was 1.6 points on the MMSE. The differences in cognitive decline were statistically significant (p  = 0.046) among the three diagnosis groups, AD participants showed the greatest decline, of 2.3 points. In addition to lower education (p  = 0.010), higher scores on the Neuropsychiatric Inventory (NPI) sub-syndromes psychosis (p  < 0.001) and hyperactivity (p  = 0.002) were associated with higher rates of cognitive decline. In contrast, higher scores on the NPI affect cluster were associated with lower levels of cognitive decline (p  < 0.001). Conclusion: Different YOD subtypes show different rates of decline in cognitive functioning, and this decline seems less progressive compared to those observed in studies in late-onset AD. Further research is needed to evaluate whether managing neuropsychiatric symptoms can positively influence the decline of cognitive function. Show more

Keywords: Cognitive decline, progression of dementia, young onset dementia

DOI: 10.3233/JAD-170859

Citation: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 343-351, 2018

Authors: Koedam, Esther L.G.E. | Lauffer, Vivian | van der Vlies, Annelies E. | van der Flier, Wiesje M. | Scheltens, Philip | Pijnenburg, Yolande A.L.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is the most common cause of dementia at older age. Although less prevalent before the age of 65 years, it is still the most frequent cause of early-onset dementia followed by frontotemporal dementia. The typical presentation of AD is memory dysfunction, however, presentations with prominent cognitive impairment in other domains besides memory, like prominent apraxia, language problems, or executive dysfunction, may occur and are relatively more common in early-onset AD. In this retrospective descriptive study, we determined the prevalence of non-memory presentations in a large sample of early-onset AD patients compared to late-onset AD. The clinical files …of 270 patients with AD starting before the age of 65 years and 90 patients with late-onset AD (⩾ 65 years) were reviewed to assess clinical characteristics. Patients were classified as memory presentation and non-memory presentation according to their clinical presentation. The mean age of the early-onset group was 56 ± 5 years and 74 ± 6 years for the late-onset group. A third of the early-onset AD group presented with non-memory symptoms compared to only 6% in the late-onset group (p < 0.001). Within the group with non-memory presentations, apraxia/visuospatial dysfunction was the most prevalent presenting symptom (12%). Patients with early-onset AD often present with a non-memory phenotype, of which apraxia/visuospatial dysfunction is the most common presenting symptom. Atypical presentations of AD should be considered in the clinical differential diagnosis of early-onset dementia. Show more

Keywords: Alzheimer's disease, clinical presentation, dementia, early onset

DOI: 10.3233/JAD-2010-1337

Citation: Journal of Alzheimer's Disease, vol. 19, no. 4, pp. 1401-1408, 2010

Authors: Möller, Christiane | Dieleman, Nikki | van der Flier, Wiesje M. | Versteeg, Adriaan | Pijnenburg, Yolande | Scheltens, Philip | Barkhof, Frederik | Vrenken, Hugo

Article Type: Research Article

Abstract: Background: The involvement of frontostriatal circuits in frontotemporal dementia (FTD) suggests that deep gray matter structures (DGM) may be affected in this disease. Objective: We investigated whether volumes of DGM structures differed between patients with behavioral variant FTD (bvFTD), Alzheimer's disease (AD), and subjective complaints (SC) and explored relationships between DGM structures, cognition, and neuropsychiatric functioning. Methods: For this cross-sectional study, we included 24 patients with FTD and matched them based on age, gender, and education at a ratio of 1:3 to 72 AD patients and 72 patients with SC who served as controls. Volumes of hippocampus, amygdala, thalamus, caudate …nucleus, putamen, globus pallidus, and nucleus accumbens were estimated by automated segmentation of 3D T1-weighted MRI. MANOVA with Bonferroni adjusted post-hoc tests was used to compare volumes between groups. Relationships between volumes, cognition, and neuropsychiatric functioning were examined using multivariate linear regression and Spearman correlations. Results: Nucleus accumbens and caudate nucleus discriminated all groups, with most severe atrophy in FTD. Globus pallidus volumes were smallest in FTD and discriminated FTD from AD and SC. Hippocampus, amygdala, thalamus, and putamen were smaller in both dementia groups compared to SC. Associations between amygdala and memory were found to be different in AD and FTD. Globus pallidus and nucleus accumbens were related to attention and executive functioning in FTD. Conclusion: Nucleus accumbens, caudate nucleus, and globus pallidus were more severely affected in FTD than in AD and SC. The associations between cognition and DGM structures varied between the diagnostic groups. The observed difference in volume of these DGM structures supports the idea that next to frontal cortical atrophy, DGM structures, as parts of the frontal circuits, are damaged in FTD rather than in AD. Show more

Keywords: Alzheimer's disease, atrophy, basal ganglia, frontotemporal dementia

DOI: 10.3233/JAD-141230

Citation: Journal of Alzheimer's Disease, vol. 44, no. 2, pp. 635-647, 2015

Authors: Willemse, Eline A.J. | Durieux-Lu, Sisi | van der Flier, Wiesje M. | Pijnenburg, Yolande A.L. | de Jonge, Robert | Teunissen, Charlotte E.

Article Type: Research Article

Abstract: Progranulin (PGRN) levels in blood and cerebrospinal fluid (CSF) are increasingly studied as potential markers for neurodegenerative disorders. We aimed to 1) characterize two commercially available PGRN ELISAs on several assay validation parameters, 2) assess the stability of PGRN in serum and CSF under pre-analytical conditions, and 3) compare stability in the two assays. Intra- and inter-assay variation, inter-lot variation, linearity, lower limit of detection, and kit correlations were assessed for the Adipogen and R&D PGRN ELISA kits. Blood and serum samples were experimentally exposed to ≤9 freeze/thaw cycles, delayed processing for ≤24 h at room temperature and 4°C, and to …temperature stability tests for ≤3 weeks at –20°C, 4°C, room temperature, and 37°C. Both commercial PGRN ELISA kits showed acceptable ranges for intra- and inter-assay variation, where the R&D kit performed more accurate than the Adipogen kit, especially for inter-assay variation (intra-assay serum: 6.7 and 8.3%, respectively; inter-assay serum: 9.2 and 21.0%; intra-assay CSF: 3.6 and 12.0%; inter-assay CSF: 16.0 and 44.5%). Absolute serum PGRN concentrations were 1.9-fold higher in Adipogen than R&D (p  < 0.001) and strongly correlated between both kits (ρ = 0.86, p  < 0.0001) and CSF PGRN levels were on the borderline of detection in both kits. PGRN was typically stable under all pre-analytical conditions addressed, although two weeks at 37°C resulted in decreased PGRN concentrations in CSF, only when using the Adipogen kit. These results support further examination of PGRN as a potential marker in neurodegenerative diseases, since PGRN is stable in serum and CSF and can be measured using ELISA kits from several providers. Show more

Keywords: Cerebrospinal fluid, human progranulin protein, ELISA, method comparison, pre-analytical variation, protein stability, serum

DOI: 10.3233/JAD-160061

Citation: Journal of Alzheimer's Disease, vol. 53, no. 1, pp. 107-116, 2016

Authors: Zhutovsky, Paul | Vijverberg, Everard G.B. | Bruin, Willem B. | Thomas, Rajat M. | Wattjes, Mike P. | Pijnenburg, Yolande A.L. | van Wingen, Guido A. | Dols, Annemiek

Article Type: Research Article

Abstract: Background: Patients with behavioral variant of frontotemporal dementia (bvFTD) initially may only show behavioral and/or cognitive symptoms that overlap with other neurological and psychiatric disorders. The diagnostic accuracy is dependent on progressive symptoms worsening and frontotemporal abnormalities on neuroimaging findings. Predictive biomarkers could facilitate the early detection of bvFTD. Objective: To determine the prognostic accuracy of clinical and structural MRI data using a support vector machine (SVM) classification to predict the 2-year clinical follow-up diagnosis in a group of patients presenting late-onset behavioral changes. Methods: Data from 73 patients were included and divided into probable /definite bvFTD (n  = 18), neurological …(n  = 28), and psychiatric (n  = 27) groups based on 2-year follow-up diagnosis. Grey-matter volumes were extracted from baseline structural MRI scans. SVM classifiers were used to perform three binary classifications: bvFTD versus neurological and psychiatric, bvFTD versus neurological, and bvFTD versus psychiatric group(s), and one multi-class classification. Classification performance was determined for clinical and neuroimaging data separately and their combination using 5-fold cross-validation. Results: Accuracy of the binary classification tasks ranged from 72–82% (p  < 0.001) with adequate sensitivity (67–79%), specificity (77–88%), and area-under-the-receiver-operator-curve (0.80–0.9). Multi-class accuracy ranged between 55–59% (p  < 0.001). The combination of clinical and voxel-wise whole brain data showed the best performance overall. Conclusion: These results show the potential for automated early confirmation of diagnosis for bvFTD using machine learning analysis of clinical and neuroimaging data in a diverse and clinically relevant sample of patients. Show more

Keywords: behavioral variant frontotemporal dementia, classification, magnetic resonance imaging, prognosis, support vector machine

DOI: 10.3233/JAD-181004

Citation: Journal of Alzheimer's Disease, vol. 68, no. 3, pp. 1229-1241, 2019

Authors: Ducharme, Simon | Pearl-Dowler, Leora | Gossink, Flora | McCarthy, Jillian | Lai, Jimmy | Dickerson, Bradford C. | Chertkow, Howard | Rapin, Lucile | Vijverberg, Everard | Krudop, Welmoed | Dols, Annemieke | Pijnenburg, Yolande

Article Type: Research Article

Abstract: Background: Differentiating early behavioral variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) is complex and biomarkers have limited accuracy, leading to inaccurate diagnoses. Objectives: Develop a simple bedside clinical tool to differentiate bvFTD from PPD. Methods: A checklist of clinical features differentiating bvFTD from PPD was developed based on literature and clinical experience. The checklist was filled prospectively for 29 consecutive patients (Montreal Neurological Hospital) with late-onset (≥ age 40) behavioral changes suggestive of bvFTD. The checklist was subsequently retrospectively completed on the baseline visit (N = 137) of the Late-Onset Frontal Lobe study (Amsterdam). In both cohorts, patients were followed …2 years to establish a final best clinical diagnosis, categorizing patients into Probable FTD (N = 46), Possible FTD (N = 8), Other Cognitive Disorder (N = 36), Other Neurological Disorder (N = 10), or PPD (N = 66). Results: All items distinguished the two groups except “duration more than 5 years”, which was removed to create a final 17-item version. Mean checklist scores were significantly different across all groups (Oneway ANOVA F(4,161) = 27.462, p  < 0.001). The PPD group had lower scores than all other dementia categories, with the largest difference between Probable FTD ( X ¯ = 12.04) and PPD ( X ¯ = 7.48). A score ≥11 was found to be strongly indicative of bvFTD (specificity 93.9%, sensitivity 71.1%, PPV 89.2%). Scores ≤8 were strongly indicative of a PPD (specificity 91.3%, sensitivity 77.3%, PPV 92.7%). Patient with scores of 9–10 are considered indeterminate. Conclusions: Although further prospective validation is required, the “FTD vs PPD Checklist” could provide a simple tool to improve diagnostic accuracy, particularly in non-specialized settings. Show more

Keywords: Behavioral variant frontotemporal dementia, diagnosis, frontotemporal dementia, psychiatric disorders, scale

DOI: 10.3233/JAD-180839

Citation: Journal of Alzheimer's Disease, vol. 67, no. 1, pp. 113-124, 2019

Authors: Gossink, Flora T. | Dols, Annemieke | Krudop, Welmoed A. | Sikkes, Sietske A. | Kerssens, Cora J. | Prins, Niels D. | Scheltens, Philip | Stek, Max L. | Pijnenburg, Yolande A.L.

Article Type: Research Article

Abstract: While psychiatric misdiagnosis is well-known in behavioral variant frontotemporal dementia (bvFTD), a systematic evaluation of standardized criteria for psychiatric disorders in bvFTD is still missing. Our aim was to define frequency and character of DSM-IV psychiatric disorders among patients with probable and definite bvFTD compared to possible bvFTD, other neurodegenerative diseases, and psychiatric diagnoses, using MINI-International Neuropsychiatric Interview. We additionally compared psychiatric prodromes between these groups. Subjects were participants of the late-onset frontal lobe (LOF) study, a longitudinal multicenter study. In each patient, after baseline diagnostic procedure, a neurologist and geriatric psychiatrist made a joint clinical diagnosis. Independently, a structured …diagnostic interview according to DSM-IV and ICD-10 criteria (MINI-Plus) was performed by a trained professional blinded to clinical diagnosis. Out of 91 patients, 23 with probable and definite bvFTD, 3 with possible bvFTD, 25 with a non bvFTD neurodegenerative disease, and 40 with a clinical psychiatric diagnosis were included. Overall frequency of formal current and past psychiatric disorders in probable and definite bvFTD (21.7% current, 8.7% past) did not differ from other neurodegenerative diseases (12.0% current, 16.0% past) or possible bvFTD (66.7% current, 66.7% past), but was less than in patients with a clinical psychiatric diagnosis (57.5% current, 62.5% past; p  <  0.01). In probable and definite bvFTD unipolar mood disorders were most common. Formally diagnosed psychiatric disorders are not overrepresented in probable bvFTD, suggesting that psychiatric misdiagnosis in bvFTD can be reduced by strictly applying diagnostic criteria. In suspected bvFTD close collaboration between neurologists and psychiatrists will advance diagnostics and subsequent treatment. Show more

Keywords: Behavior, behavioral variant frontotemporal dementia, DSMIV criteria, ICD-10 criteria, misdiagnosis, neurology, psychiatric disorders, psychiatry

DOI: 10.3233/JAD-151198

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 1249-1256, 2016

Authors: Verwey, Nicolaas A. | Kester, Maartje I. | van der Flier, Wiesje M. | Veerhuis, Robert | Berkhof, Hans | Twaalfhoven, Harry | Blankenstein, Marinus A. | Scheltens and, Philip | Pijnenburg, Yolande A.L.

Article Type: Research Article

Abstract: To determine the additional value of cerebrospinal fluid (CSF) amyloid-β1-40 (Aβ40 ) next to amyloid-β1-42 (β42 ), total tau (Tau), and tau phosphorylated at threonine-181 (pTau) to distinguish patients with frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), and controls, we measured CSF levels of Aβ40 , Aβ42 , pTau, and Tau in 55 patients with FTLD, 60 with AD, and 40 control subjects. Logistic regression was used to identify biomarkers that best distinguished the groups. Additionally, a decision tree (cost=test method; Matlab 7.7) was used to predict diagnosis selecting the best set of biomarkers with the optimal cut-off. Logistic regression …showed that Aβ42 and pTau CSF levels provided optimal distinction between AD and FTLD. A combination of Aβ42 , Tau, and Aβ40 optimally discriminated FTLD from controls and AD from controls. The decision tree used Aβ42 (cut-off 578 pg/ml) to identify AD (positive predictive value (PPV) 97%), followed by Tau (cut-off 336 pg/ml) to identify FTLD (PPV 67%), and in the last step, Aβ40 (cut-off 10 ng/ml) was used to differentiate controls (PPV 68%). Applying CSF Aβ40 levels in the model, the PPV of diagnosis increased to 75% as opposed to 70% when only Aβ42 and Tau were used. CSF Aβ40 levels added to the conventional CSF biomarkers increases the potential to discriminate subjects with dementia from controls. Our findings favor the implementation of CSF Aβ40 in differential diagnosis between FTLD, AD, and control subjects. Show more

Keywords: Alzheimer's disease, amyloid-β, biomarker, cerebrospinal fluid, ELISA, frontotemporal lobar degeneration

DOI: 10.3233/JAD-2010-1392

Citation: Journal of Alzheimer's Disease, vol. 20, no. 2, pp. 445-452, 2010