To combine scientific research (fundamental, translational, clinical and epidemiological), patient care and education in dementia in order to
- implement newest research findings in clinical practice and improve dementia diagnostics;
- find a cure for diseases underlying dementia;
- prevent dementia. In order to achieve long term goals we train early career dementia clinicians and investigators.
Research Activities
Our research takes place on multiple levels and in multiple fields of interest at the same time in the same research population.
Overall, our current research focuses on the levels:
- Fundamental (molecular genetics, metabolics, proteomics, neuropathology, genetic mouse models)
- Translational (follow up study in presymptomatic carriers of genetic deficits causing frontotemporal dementia, mouse models of genetic deficits in dementia with a behavioural component, implementation of quantitative neuroimaging aided diagnosis setting in clinical daily practice)
- Clinical (biomarkers in neuroimaging, neuropsychological, neuropsychiatry, assessment of functional abilities, (I)ADL). We participate in Parelsnoer Neurodegenerative disease (biobanking). We monitor for rare transmissible forms of dementia, in particular prion diseases to prevent transmission in the general population.
- Epidemiological (implementation of knowledge from ERGO study in clinical practice, neuroimaging, prevention)
In many projects, national and international alliances have been formed, for example multiple JPND projects and the Genetic FTD Initiative (Europe and Canada) in FTD research and the participation in international medication trials. Nationally participating in the Medical Delta and Parelsnoer initiative. In the future, our (inter)national collaborations will be deepened; research activities will be continued at all levels.
Collaborations
In many projects, national and international alliances have been formed, for example multiple JPND projects and the Genetic FTD Initiative (Europe and Canada) in FTD research and the participation in international medication trials. Nationally participating in the Medical Delta and Parelsnoer initiative. In the future, our (inter)national collaborations will be deepened; research activities will be continued at all levels.
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Contributions
PhD education is one of the most important pillars of research within the ACE Alzheimercentrum. Dementia research in our groups is performed by at least 23 PhD students.
We are planning to set up a minor on dementia research, diagnostics and care for the upcoming years. We are involved in the new Bachelor and Master programme 'Clinical Technology', as well as the existing curriculum for Ba and MSc Medicine, Neuroscience, Psychology, Physics. Student research projects, Ba and MSc can be performed in a clinical or research setting. Our PIs give lectures on dementia research and care in PhD courses (Netherlands Institute for Health Sciences in research methods courses such as biostatistics and clinical and genetic data) and clinical resident courses (nascholing Biemond, congresses).
Feedback from evaluations by students and study coordinators is considered, and improvement is an integral part of education performed in our ACE. International students are among the Ba, MSc and PhDs (Eastern Europe, South America, China, Pakistan), although they cannot be a part of daily clinical practice, as a good understanding of the Dutch language is crucial for dementia diagnostics.
Care Activities
More than 80% of all patients are referred for second opinion diagnostics (academic care). Departments involved in diagnostic work-up within our center are the dept. Geriatrics, Neurology, Radiology, Psychiatry, Clinical Genetics. Diagnosis setting takes place in a multidisciplinary consensus meeting.
In 2011-2012 we developed a successful Care Pathway for the Alzheimercentrum, involving all disciplines, which was tracked and monitored. For this project we received the award of €30.000,- from the board of directors of the Erasmus MC. In the upcoming year we will collaborate with ICHOM dementia, and implement their guideline on quality in daily clinical practice. Feedback from quality reports, such as visitations have an impact on the improvement of patient care in the ACE. Dept. Neurology, Geriatrics and Radiology are frequently visited.
One of the recent improvements in dementia diagnostics is to reduce the work load of clinical residents in the Neurology dept. It is our main aim to implement research results of the ACE in daily clinical practice. We have worked on innovative care according to latest guidelines for the past twenty years. Good examples are the international collaboration in diagnostic criteria working groups. Another example is the implementation of quantitative neuroimaging dementia diagnostics in this ACE.
Societal Relevance to Research, Education and Patient Care
Our ACE is highly involved in the development of educational/public/societal knowledge on dementia through our collaboration with several patient organizations (Alzheimer Nederland and FTD lotgenoten). We are highly involved in the project 'dementievriendelijke samenleving' as well as the National Dementia Plan 'Deltaplan dementie' and its scientific pillar 'Memorabel'. We furthermore are involved in the development of clinical, therapeutic and research guidelines in international collaborations for several neurodegenerative diseases, in particular frontotemporal dementia related disorders.
We have been endorsed as center of expertise for the rare disorders Frontotemporal dementia and Creutzfeldt-Jakob by the Dutch Minister of Health, Welfare and Sports, which obligates us to contribute to research in diagnostics and new treatments, but also public knowledge on these rare diseases. We collaborate in multiple research consortia focused on prevention and development of therapeutics (JPND, national initiatives).
Furthermore, we have an innovative character in all levels of research, fundamental, clinical, translational and epidemiological. We make use of beyond the state of the art genetic research, in clinical and population based samples including gene discovery of common and rare variants. We are part of the a H2020 project PRECEEDI in which we are translating genetic findings into value based health care.
Viability of Research, Education and Patient Care
Research, education and patient care in dementia require a multidisciplinary approach. In our research and care teams we involve students (PhD and MSc), early career clinicians and researchers as well as established clinicians and researchers. This way we keep our team, the research and patient care viable.
All of our PhD students are stimulated to spend some of their research time abroad with one of our many international collaborators (Cambridge, Harvard, Mayo Clinic, UCL). Almost all of the publications of PhD students are international collaborations, and students present their own work on international conferences in the dementia-related field (AAIC conference, conference on frontotemporal dementias, movement disorder conference, parkinson's disease conference).
We are currently working on a bibliometric network analysis.
Key and relevant publications of the last five years
- Dopper EG, et al. … van Swieten JC. Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia. Neurology. 2014 Jul
- Seelaar H, Rohrer JD, Pijnenburg YAL, Fox NC, Van Swieten JC. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J Neurol Neurosur Psychiatry 2011;82(5):476-486
- Rascovsky K, et al. … van Swieten JC, … Miller BL. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia Brain.
- Renton AE, et al. … van Swieten JC, … Traynor BJ. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD.
- Bron EE, ... Papma JM, Steketee RM, ... Meijboom R, ... van Swieten JC, Niessen WJ, Klein S. Alzheimer's Disease Neuroimaging Initiative. Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: the CADDementia challenge. Neuroimage. 2015 May 1;111:562-79.
- Papma JM, de Groot M, de Koning I, Mattace-Raso FU, van der Lugt A, Vernooij MW, Niessen WJ, van Swieten JC, Koudstaal PJ, Prins ND, Smits M. Cerebral small vessel disease affects white matter microstructure in mild cognitive impairment. Hum Brain Mapp 2014 Jun;5(6):2836-2851
- Nijholt DAT, et al. Endoplasmic reticulum stress activates autophagy but not the proteasome in neuronal cells: implications for Alzheimer's disease. Cell Death Differ 2011;18(6):1071-81
- Lambert J-C, Ibrahim-Verbaas CA, ... van Duijn CM, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nature Genetics 2013;45(12):1452-1458
- Bron EE, Steketee RME, ... van Swieten JC, ... Niessen WJ, Smits M, Klein S. Diagnostic classification of arterial spin labeling and structural MRI in presenile early stage dementia. Hum Brain Mapp 2014;35(9):4916-4931
- Hukema RK, Riemslagh FW, ... J.C. van Swieten, R. Willemsen. A new inducible transgenic mouse model for C9orf72-associated GGGGCC repeat expansion supports a gain-of-function mechanism in C9orf72-associated ALS and FTD. Acta Neuropathol Commun 2014;2:166.
PhD theses of the last five years
- Esther E. Bron – Advanced MRI analysis for computer-aided diagnosis of dementia (2016)
- Rebecca Steketee – Advanced MR neuroimaging in early stage presenile dementia (2016)
- Elise GP Dopper – Familial frontotemporal lobar degeneration (2015)
- Casper de Boer – Visuomotor integration in neurodegenerative brains (2015)
- Carla A. Ibrahim-Verbaas – A genetic epidemiological study of dementia and cognitive functions (2014)
- Marius De Groot – Cross-subject image analysis in diffusion brain MRI (2014)
- Linda IJsselstijn – Serum proteomics in dementia (2013)
- Janne M. Papma – Functional neuroimaging in dementia (2012)
- Laura Donker-Kaat - Progressive supranuclear Palsy, expanding the clinical and genetic spectrum (2011)
- Harro Seelaar – Frontotemporal dementia, clinical genetic and pathological heterogeneity (2011)