Yolande A L Pijnenburg

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (123)518.69 Total impact

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    ABSTRACT: To investigate trajectories of cognitive decline in patients with different types of dementia compared to controls in a longitudinal study.
    Psychological medicine. 09/2014;
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    ABSTRACT: We aimed to assess the impact of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease on decision making and patient management in a tertiary memory clinic.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 08/2014; · 14.48 Impact Factor
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    ABSTRACT: Genetic factors are important in all forms of dementia, especially in early onset dementia. The frequency of major gene defects in dementia has not been investigated in the Netherlands. Furthermore, whether the recently in a FTD family identified PRKAR1B gene is associated with an Alzheimer's disease (AD) like phenotype, has not been studied. With this study, we aimed to investigate the mutation frequency of the major AD and FTD genes and the PRKAR1B gene in a well-defined Dutch cohort of patients with early onset dementia. Mutation analysis of the genes PSEN1, APP, MAPT, GRN, C9orf72 and PRKAR1B was performed on DNA of 229 patients with the clinical diagnosis AD and 74 patients with the clinical diagnosis FTD below the age of 70 years. PSEN1 and APP mutations were found in, respectively 3.5 and 0.4 % of AD patients, and none in FTD patients. C9orf72 repeat expansions were present in 0.4 % of AD and in 9.9 % of FTD patients, whereas MAPT and GRN mutations both were present in 0.4 % in AD patients, and in 1.4 % resp. 2.7 % in FTD patients. We did not find any pathogenic mutations in the PRKAR1B gene. PSEN1 mutations are the most common genetic cause in Dutch AD patients, whereas MAPT and GRN mutations were found in less than 5 percent. C9orf72 repeat expansions were the most common genetic defect in FTD patients. No pathogenic PRKAR1B mutations were found in the early onset AD and FTD patients of our study.
    Journal of neurology. 08/2014;
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    ABSTRACT: To compare pseudo-continuous arterial spin-labelled (PCASL) magnetic resonance imaging (MRI) measured quantitative cerebral blood flow (CBF) of patients with frontotemporal dementia (FTD), dementia with Lewy Bodies (DLB), Alzheimer's disease (AD) and controls, in a region of interest (ROI) and voxel-wise fashion.
    European radiology. 07/2014;
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    ABSTRACT: BACKGROUND: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. METHODS: We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10(-8)) single-nucleotide polymorphisms. FINDINGS: We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10(-8)). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10(-8); odds ratio=1·204 [95% CI 1·11-1·30]), rs9268856 (p=5·51 × 10(-9); 0·809 [0·76-0·86]) and rs1980493 (p value=1·57 × 10(-8), 0·775 [0·69-0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10(-7); 0·814 [0·71-0·92]). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. INTERPRETATION: Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD
    The Lancet Neurology 07/2014; 3(7):686-99. · 23.92 Impact Factor
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    ABSTRACT: Co-morbidity and frailty are common in Alzheimer's disease (AD) and may contribute to the heterogeneity in clinical manifestations of the disease. We cross-sectionally investigated whether co-morbidity and frailty were independently associated with the clinical manifestation of AD in the 4C-Dementia study; a multicenter, longitudinal study in newly diagnosed AD patients. Clinical manifestation was operationalized using a composite of cognitive performance (neuropsychological assessment), activities of daily living functioning (Disability Assessment for Dementia; DAD) and neuropsychiatric symptoms (Neuropsychiatric Inventory). As predictors of prime interest, co-morbidity was determined using the Cumulative Illness Rating Scale (CIRS-G) and frailty by the Fried criteria. In total, 213 AD patients participated (mean age 75 ± 10 years; 58% females). In linear regression models adjusted for age, gender, education, and disease duration, CIRS-G (β = -0.21, p < 0.01) and frailty (β = -0.34, p < 0.001) were separately associated with clinical AD manifestation. However, CIRS-G (β = -0.12, p = 0.12) lost statistical significance when both were combined (frailty: β = -0.31, p < 0.001). Models with the individual components of clinical AD manifestation as dependent variables show significant associations between cognitive performance and CIRS-G (β = -0.22, p = 0.01), and between DAD and frailty (β = -0.37, p < 0.001). Our findings indicate that physical health and clinical AD manifestation are associated. This association may be responsible for part of the heterogeneity in the presentation of AD. This emphasizes the importance of adequate assessment of co-morbid medical conditions and frailty in participants with AD.
    Journal of Alzheimer's disease: JAD 06/2014; · 4.17 Impact Factor
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    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.
    Journal of Alzheimer's disease: JAD 03/2014; · 4.17 Impact Factor
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    ABSTRACT: Aim: To assess the reliability and validity of the Van Heugten test for apraxia (VHA), developed for and used in stroke patients, in a memory clinic population. Furthermore, we assess the presence and severity of apraxia in mild cognitive impairment (MCI) and Alzheimer's disease (AD) and investigate which AD patients are likely to develop apraxia. Methods: We included 90 controls (age: 60 ± 9 years, MMSE: 28 ± 2), 90 MCI patients (age: 65 ± 7 years, MMSE: 26 ± 2) and 158 AD patients (age: 66 ± 8 years, MMSE: 20 ± 5). Apraxia was evaluated by the VHA assessing ideational and ideomotor praxis. We retested 20 patients to assess reliability. Results: Intrarater reliability was 0.88 and interrater reliability was 0.73. AD patients performed worse on the VHA (median: 88; range: 51-90) than controls (median: 90; range: 88-90) and MCI patients (median: 89; range: 84-90) (both p < 0.001). Apraxia was prevalent in 35% of AD patients, in 10% of MCI and it was not observed in controls (0%; p < 0.001). In AD, dementia severity was the main risk for apraxia; 15% of mildly versus 52% of moderately demented patients had apraxia (OR = 6.7, 95% CI 2.9-15.6). The second risk factor was APOE genotype. APOE ε4 noncarriers (47%) were at increased risk compared to carriers (30%) (OR = 2.1, 95% CI 1-4.7). Conclusion: Apraxia can be reliably measured with the VHA and is present in a proportion of patients with MCI and AD. The presence of apraxia in AD is related to dementia severity and APOE ε4. © 2014 S. Karger AG, Basel.
    Dementia and Geriatric Cognitive Disorders 03/2014; 38(1-2):55-64. · 2.79 Impact Factor
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    ABSTRACT: Characteristic frontotemporal abnormalities on structural or functional neuroimaging are mandatory for a diagnosis of probable behavioral variant of frontotemporal dementia (bvFTD) according to the new criteria. 18-Fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging is commonly reserved for patients with suspected bvFTD without characteristic structural neuroimaging results. We studied the diagnostic value of 18F-FDG-PET in these patients.Methods:The 18F-FDG-PET was performed in 52 patients with suspected bvFTD but lacking characteristic structural neuroimaging results. The clinical diagnosis of bvFTD in the presence of functional decline (bvFTD/fd+) after a follow-up period of 2 years was used as a golden standard.Results:The sensitivity of 18F-FDG-PET for bvFTD/fd+ was 47% at a specificity of 92%. The differential diagnosis comprised alternative neurodegenerative and psychiatric disorders and a benign phenocopy of bvFTD.Conclusions:The 18F-FDG-PET is able to identify nearly half of the patients with bvFTD who remain undetected by magnetic resonance imaging. In our selected group, high specificity enables exclusion of psychiatric and other neurodegenerative disorders.
    American Journal of Alzheimer s Disease and Other Dementias 02/2014; · 1.52 Impact Factor
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    ABSTRACT: Measuring impairments in "instrumental activities of daily living" (IADL) is important in dementia, but challenging due to the lack of reliable and valid instruments. We recently developed the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q; note 1). We aim to investigate the diagnostic accuracy of the A-IADL-Q for dementia in a memory clinic setting. Patients visiting the Alzheimer Center of the VU University Medical Center with their informants between 2009 and 2011 were included (N = 278). Diagnoses were established in a multidisciplinary consensus meeting, independent of the A-IADL-Q scores. An optimal A-IADL-Q cutoff point was determined, and sensitivity and specificity were calculated. Area under the curves (AUCs) were compared between A-IADL-Q and "disability assessment of dementia" (DAD). The additional diagnostic value of the A-IADL-Q to Mini-Mental State Examination (MMSE) was examined using logistic regression analyses. Dementia prevalence was 50.5%. Overall diagnostic accuracy based on the AUC was 0.75 (95% confidence interval [CI]: 0.70-0.81) for the A-IADL-Q and 0.70 (95% CI: 0.63-0.77) for the DAD, which did not differ significantly. The optimal cutoff score for the A-IADL-Q was 51.4, resulting in sensitivity of 0.74 and specificity of 0.64. Combining the A-IADL-Q with the MMSE improved specificity (0.94), with a decline in sensitivity (0.55). Logistic regression models showed that adding A-IADL-Q improved the diagnostic accuracy (Z = 2.55, P = .011), whereas the DAD did not. In this study, we showed a fair diagnostic accuracy for A-IADL-Q and an additional value in the diagnosis of dementia. These results support the role of A-IADL-Q as a valuable diagnostic tool.
    Journal of Geriatric Psychiatry and Neurology 12/2013; 26(4):244-50. · 3.53 Impact Factor
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    ABSTRACT: In Alzheimer's disease (AD), some patients present with cognitive impairment other than episodic memory disturbances. We evaluated whether occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) could account for differences in cognitive domains affected. In 329 patients with AD, we assessed five cognitive domains: memory, language, visuospatial functioning, executive functioning, and attention. Magnetic resonance imaging (MRI) was rated visually for the presence of MTA and PA. Two-way analyses of variance were performed with MTA and PA as independent variables, and cognitive domains as dependent variables. Gender, age, and education were covariates. As PA is often encountered in younger patients, analyses were repeated after stratification for age of onset (early onset, ≤ 65 years). The mean age of the participants was 67 years, 175 (53%) were female, and the mean Mini-Mental State Examination (score ± standard deviation) was 20 ± 5 points. Based on dichotomized magnetic resonance imaging ratings, 84 patients (26%) had MTA and PA, 98 (30%) had MTA, 57 (17%) had PA, and 90 (27%) had neither. MTA was associated with worse performance on memory, language, and attention (all, P < .05), and PA was associated with worse performance on visuospatial and executive functioning (both, P < .05). Stratification for age showed in patients with late-onset AD (n = 173) associations between MTA and impairment on memory, language, visuospatial functioning, and attention (all, P < .05); in early-onset AD (n = 156), patients with PA tended to perform worse on visuospatial functioning. Regional atrophy is related to impairment in specific cognitive domains in AD. The prevalence of PA in a large set of patients with AD and its association with cognitive functioning provides support for the usefulness of this visual rating scale in the diagnostic evaluation of AD.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 11/2013; · 14.48 Impact Factor
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    ABSTRACT: ABSTRACT Background: Little is known about care needs in young-onset dementia (YOD) patients, even though this information is essential for service provision and future care planning. We explored: (1) care needs of people with YOD, (2) the level of agreement within patient-caregiver dyads on care needs, and (3) the longitudinal relationship between unmet needs and neuropsychiatric symptoms. Methods: A community-based prospective study of 215 YOD patients-caregiver dyads. Care needs were assessed with the Camberwell Assessment of Need for the Elderly. The level of agreement between patient and caregivers' report on care needs was calculated using κ coefficients. The relationship between unmet needs and neuropsychiatric symptoms over time, assessed with the Neuropsychiatric Inventory, was explored using linear mixed models. Results: Patients and caregivers generally agreed on the areas in which needs occurred. Only modest agreement existed within patient-caregiver dyads regarding whether needs could be met. Patients experienced high levels of unmet needs in areas such as daytime activities, social company, intimate relationships, and information, leading to an increase in neuropsychiatric symptoms. Conclusions: Our findings indicate that in YOD, there are specific areas of life in which unmet needs are more likely to occur. The high proportions of unmet needs and their relationship with neuropsychiatric symptoms warrant interventions that target neuropsychiatric symptoms as well as the prevention of unmet needs. This underlines the importance of the periodic investigation of care needs, in which patient and caregiver perspectives are considered complementary.
    International Psychogeriatrics 09/2013; · 2.19 Impact Factor
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    ABSTRACT: To identify the existence of discrete cognitive subtypes among memory clinic patients without dementia and test their prognostic values. In a retrospective cohort study of 635 patients without dementia visiting the Alzheimer centers in Maastricht or Amsterdam, latent profile analysis identified cognitive subtypes based on immediate and delayed memory recall, delayed recognition, information-processing speed, attention, verbal fluency, and executive functions. Time to dementia was tested in weighted Cox proportional hazard models adjusted for confounders. Five latent classes represented participants with high-normal cognition (15%), low-normal cognition (37%), primary memory impairment in recall (MI) (36%), memory impairment in recall and recognition (MI+) (5%), and primary nonmemory impairment (NMI) (6%). Compared with low-normal cognition, participants with NMI had the highest risk of dementia (hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.46-10.18) followed by MI (HR = 3.05, 95% CI = 2.09-4.46) and MI+ (HR = 3.26, 95% CI = 1.72-6.17), while participants with high-normal cognition had the lowest risk (HR = 0.24, 95% CI = 0.07-0.80). Subtypes further showed differential relationships with dementia types, with MI and MI+ most often converting to Alzheimer-type dementia and NMI to other forms of dementia. Cognitive subtypes can be empirically identified in otherwise heterogeneous samples of memory clinic patients and largely confirm current strategies to distinguish between amnestic and nonamnestic impairment. Studying more homogeneous cognitive subtypes may improve understanding of disease mechanisms and outcomes.
    Neurology 08/2013; · 8.25 Impact Factor
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    ABSTRACT: Young-onset dementia (YOD) causes specific challenges and issues that are likely to affect health-related quality of life (HRQOL). This study explored patient and caregiver HRQOL and its association with unmet needs in YOD. A cross-sectional design was used to study 215 community-dwelling YOD patients and their primary caregivers. Multiple linear regression analyses were performed to determine the relationship between unmet needs assessed with the Camberwell Assessment of Need for the Elderly scale and patient and caregiver HRQOL, controlling for other variables such as demographic characteristics, patient functional status, neuropsychiatric symptoms, and caregiver sense of competence. Patient HRQOL was not associated with unmet needs. However, we found that the unmet needs of both patient and caregiver were related to several domains of caregiver HRQOL. This study shows that patient and caregiver unmet needs are related to caregiver HRQOL in YOD. However, the relationship between HRQOL and unmet needs is complex. The assessment of unmet needs within the context of HRQOL seems to be an important prerequisite for personalizing care in YOD. Adjusting supportive services to match the individual needs and preferences of these young patients and their caregivers is likely to enhance their quality of life.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 07/2013; · 3.35 Impact Factor
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    ABSTRACT: To describe the aims and design of the ongoing Late Onset Frontal Lobe Syndrome study (LOF study), a study on the spectrum of neurodegenerative and psychiatric etiologies causing behavioral changes in later life, and on the role of magnetic resonance imaging (MRI), [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and cerebrospinal fluid (CSF) biomarkers in predicting and identifying the different underlying pathologies with a special focus on the behavioral variant of frontotemporal dementia. The LOF study is an observational cross-sectional and prospective follow-up study. Patients aged 45-75 years with a frontal behavioral change consisting of apathy, disinhibition, or compulsive/stereotypical behavior were included (April 2011-2013). Patients underwent a multidisciplinary assessment by a neurologist and psychiatrist and MRI, CSF, and PET measurements at inclusion and after 2 years of follow-up. The diagnostic added value of MRI, PET, and CSF results and their predictive value will be measured after 2 years of follow-up. This is the first large-scale prospective follow-up study of patients with late-onset behavioral disorders.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 06/2013; · 3.35 Impact Factor
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    ABSTRACT: Background: This study describes the validation of a new instrument measuring instrumental activities of daily living (IADL), the Amsterdam IADL Questionnaire© (a registered copyright of the Alzheimer Center of the VU University Medical Center). This informant-based tool aimed at detecting IADL problems in incipient dementia was previously found to have a high internal consistency and test-retest reliability. Methods: Patients and their informants who visited the Alzheimer Center of the VU University Medical Center were included in this study. Item response theory was used to estimate the individuals' trait levels as a measure of IADL disability. Construct validity was tested by correlating estimated trait levels with clinical and demographic measures using Pearson's or Kendall's τ correlation coefficients. Additionally, estimated trait levels between patients with and without dementia and between patients with early- and late-onset dementia were compared using independent t tests. Results: A total of 206 informants of patients completed the Amsterdam IADL Questionnaire. The correlations between estimated trait levels and other measures were in concordance with previously formed hypotheses. Patients diagnosed with dementia (n = 93) had higher estimated trait levels than patients without dementia (n = 96), Cohen's effect size, d = 1.04, t(187) = 7.1, p < 0.001. We found no differences between early- and late-onset dementia patients. Conclusions: Results suggest that the Amsterdam IADL Questionnaire is a reliable and valid instrument in the evaluation of dementia.
    Neuroepidemiology 05/2013; 41(1):35-41. · 2.37 Impact Factor
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    ABSTRACT: We present the case of a 52-year-old man who was diagnosed with the behavioural variant of frontotemporal dementia (bvFTD) in accordance with consortium criteria from 1998. The diagnosis was questioned in the years of follow-up, since neuroimaging showed no abnormalities and no deterioration of clinical symptoms was seen. After 3 years, the diagnosis was withdrawn after the psychiatrist concluded that his low intelligence, combined with a cluster C personality and relational problems, had caused his altered behaviour. Diagnosing bvFTD is challenging because of its clinical resemblance to neurodegenerative and psychiatric illnesses. The new bvFTD consortium criteria from 2011 emphasize the importance of distinguishing possible and probable bvFTD. This can reduce the number of incorrect diagnoses. We present a flow chart based on these criteria, which could aid in improving the diagnostic process.
    Nederlands tijdschrift voor geneeskunde 01/2013; 157(42):A6370.
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    ABSTRACT: Early onset dementia (EOD) poses specific challenges and issues for both the patient and (in)formal care. This study explores the use of (in)formal care prior to institutionalization, and its association with patient and caregiver characteristics. Participants were part of a community-based prospective longitudinal study of 215 patients and their informal caregivers. Baseline data of a subsample of 215 patient-caregiver dyads were analyzed. Analyses of covariance were performed to determine correlates of (in)formal care use assessed with the Resource Utilization in Dementia (RUD)-Lite questionnaire. Informal care had a 3:1 ratio with formal care. Supervision/surveillance constituted the largest part of informal care. In more than half of cases, patients had only one informal caregiver. The amount of informal care was associated with disease severity, showing more informal care hours in advanced disease stages. Fewer informal care hours were related to more caregiver working hours, especially in younger patients. The amount of formal care was related to disease severity, behavioral problems, and initiative for activities of daily living. In EOD, it appears that family members provide most of the care. However, other social roles still have to be fulfilled. Especially in spousal caregivers of younger patients in advanced disease stages, there is a double burden of work and care responsibilities. This finding also indicates that even within the EOD group there might be important age-related differences. The relatively higher amount of formal care use during advanced disease stages suggests a postponement in the use of formal care.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 01/2013; 21(1):37-45. · 3.35 Impact Factor
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    ABSTRACT: Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face-to-face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 12/2012; · 14.48 Impact Factor

Publication Stats

2k Citations
518.69 Total Impact Points

Institutions

  • 2003–2014
    • VU University Medical Center
      • • Department of Clinical Genetics
      • • Department of Neurology
      • • Department of Clinical Neurophysiology
      Amsterdamo, North Holland, Netherlands
  • 2012–2013
    • Radboud University Nijmegen
      • Department of Primary and Community Care
      Nymegen, Gelderland, Netherlands
    • Diakonessenhuis Utrecht
      Utrecht, Utrecht, Netherlands
  • 2003–2012
    • Erasmus MC
      • Department of Neurology
      Rotterdam, South Holland, Netherlands
    • VU University Amsterdam
      • Department of Neurology
      Amsterdamo, North Holland, Netherlands
  • 2011
    • University College London
      • Department of Neurodegenerative Disease
      London, ENG, United Kingdom
  • 2010
    • Erasmus Universiteit Rotterdam
      • Department of Neurology
      Rotterdam, South Holland, Netherlands
  • 2009
    • Brighton and Sussex Medical School
      Brighton, England, United Kingdom
  • 2007
    • Radboud University Medical Centre (Radboudumc)
      • Department of Neurology
      Nymegen, Gelderland, Netherlands