Who are the partners in MODEM?

MODEM is a collaboration between twelve Dutch research institutions, including universities and medical centres. The consortium forms part of the National Dementia Strategy and receives support from ZonMw and Alzheimer Nederland.

Prof. Dr Guus Smit is MODEM’s Principal Investigator. He leads the consortium.

The research comprises five so-called pillars (see ‘What problem is it tackling?’).

The (co-)project leaders for the pillars are Prof. Elly Hol, Dr Wiep Scheper, Prof. Paul Lucassen, Prof. Dr Ronald van Kesteren, Prof. Dr Matthias van Osch, Prof. Dr Elga de Vries, Prof. Dr Pieter Jelle Visser and Dr Betty Tijms.

Collaborating partners

• Vrije Universiteit Amsterdam, lead applicant
• Amsterdam UMC
• Utrecht University Medical Centre
• Radboud UMC
• Erasmus MC
• Groningen UMC
• Leiden UMC
• Maastricht University
• University of Amsterdam
• Princess Máxima Centre
• Julius Centre
• Leeuwarden Medical Centre

MODEM’s partners have their own in-house specialists in the fields of implementation and data organisation; therefore, no external organisations are involved in these areas.

Would you like to read more about the dementia research programme? Visit zonmw.nl.

What goes wrong in dementia and (how) can this be reversed?

What happens in the brain in cases of dementia? MODEM is investigating this. The team is looking at various causes and researching how damage can be detected earlier and, where possible, treated in a more targeted manner.

The research comprises three main themes (known as ‘pillars’) and two cross-cutting work packages.

How do you replicate brain cells in the lab?

For research into dementia, it would be ideal to study brain cells from people with dementia. This is usually only possible after death, and provided the person has donated their brain. This makes conducting research difficult. That is why, in this first pillar, MODEM is working on a new method to convert skin cells from people with dementia into brain cells, such as nerve cells and glial cells (support cells). This will enable researchers to investigate in the lab exactly what goes wrong in brain tissue, without having to wait for a brain donation.

Disrupted brain networks: how do you fix that?

In our brains, millions of brain cells work together in networks. They transmit signals to one another via synapses: small connection points between the nerve cells. In the early stages of dementia, all sorts of things are already going wrong here. Often years before a person experiences any symptoms. But what exactly are these disruptions? How do you detect them? And might it even be possible to reverse them with treatment? In this pillar, MODEM focuses on these questions.

What happens to the blood-brain barrier?

The blood-brain barrier is a network of blood vessels that allows essential nutrients to pass through whilst blocking harmful substances. The barrier therefore protects the brain from any harmful substances in the blood. In people with dementia, this barrier often no longer functions properly. The question is: is damage to the blood-brain barrier a cause of dementia, or rather a consequence? MODEM is investigating this in this pillar. This consortium is also developing new techniques to better visualise these changes.

Linking disparate data to gain new insights

A great deal of data has already been collected on substances in the bodies of people with dementia. Substances in the blood, for example, as well as in cerebrospinal fluid and brain tissue. However, this data is often analysed in isolation. MODEM brings all this data together in a single analysis, within this cross-cutting work package. In this way, the researchers hope to discover patterns that point to (combinations of) specific substances which can help us identify dementia at an early stage.

Maximising impact and safeguarding ethics

To ensure that the results of the MODEM research have an impact, this consortium has dedicated a separate work package to this end. Read more about this in the Impact Plan.

See also the project information about MODEM on zonmw.nl.

Delving deep into the brain, with a practical focus

MODEM uses biomedical research to investigate exactly what goes wrong in the brain in cases of dementia. This involves both fundamental and applied research.

An ethics expert is involved at every stage of MODEM’s research, from the laboratory to clinical practice. This also applies to the sharing of results and plans for the future.

Fundamental biomedical research

To understand how dementia develops in various conditions (such as Alzheimer’s and frontotemporal dementia), MODEM researchers carry out fundamental biomedical research. They focus primarily on brain cells in the laboratory.

Skin cells from people with dementia are transformed into brain cells in the lab and cultivated into ‘mini-brains’. Researchers examine these closely: how do nerve cells communicate with one another? And what goes wrong in dementia?

They are also investigating whether external factors, such as diet or stressors, affect the connections between nerve cells in the mini-brains. The question is whether certain nutrients reduce the risk of dementia, whilst stress increases it. They are also testing whether specific substances can repair certain types of damage in nerve cells. They are comparing these results with findings from research on mice with dementia.

Applied biomedical research

To investigate whether changes in the blood-brain barrier are caused by dementia or, conversely, cause dementia, a clearer picture of that barrier is needed. That is why MODEM is using advanced imaging techniques, such as MRI and PET, to make changes in the blood-brain barrier clearer and detectable at an earlier stage. To this end, they are combining these imaging techniques with tests on the cultured mini-brains.

Data analysis

MODEM also analyses large amounts of data from studies involving large groups of people, focusing on substances found in cerebrospinal fluid and brain tissue. By looking for patterns that occur in people with and without dementia, they hope to identify so-called new biomarkers: (combinations of) substances that can be used to recognise dementia.

At the same time, MODEM maintains contact with the world outside the lab: people with dementia, doctors and other stakeholders contribute their insights to the research and to how the results can be used in the future. More on this under ‘Stakeholders’.

Insights into the causes of dementia and a step towards earlier diagnoses and treatment

MODEM will share insights into the development of dementia at conferences and in scientific journals. But it will also share this information with the people the research is intended for. Think of an article explaining what goes wrong in brain cells, how networks in the brain become disrupted, and how the blood-brain barrier breaks down. This will help raise awareness amongst people worldwide.

For an overview of publications, see zonmw.nl.

New biomarkers

In addition, MODEM aims to identify new biomarkers. These are substances found in the blood, cerebrospinal fluid or the brain that indicate dementia and can be measured via blood tests or brain scans. MODEM also aims to determine which brain processes need to be addressed at an early stage to prevent damage. Once you know that, you can move on to the next step: finding out how to modulate such brain processes and develop a treatment.

A clearer picture of the blood-brain barrier

In addition, MODEM aims to identify new biomarkers. These are substances found in the blood, cerebrospinal fluid or the brain that indicate dementia and can be measured via blood tests or brain scans.

MODEM also aims to determine which brain processes need to be addressed at an early stage to prevent damage. Once this is known, the next step is to find out how to modulate these brain processes and develop a treatment.

Creating mini-brains faster and more effectively

The methods for converting skin cells into brain cells and cultivating them into mini-brains have come a long way but still need improvement. If this is achieved, many more researchers and pharmaceutical companies will be able to use them to find out more about dementia and potential treatments. And this research can progress more quickly.

Educating colleagues, students and the public

MODEM researchers also pass on the knowledge they have gained through teaching: for example, through lectures on biomarkers, new imaging techniques or the construction of mini-brains. In this way, students and young researchers are kept up to date with the latest insights. Finally, MODEM also shares its findings with a wider public, including through the Alzheimer’s Cafés.

Increasing impact and upholding ethical standards

Research yields valuable insights into dementia, but these do not always translate into practice. To achieve greater impact, MODEM is working on this cross-cutting work package to

• improved collaboration,
• data sharing and
• clear communication.

There is also a focus on ethics. For example, is it acceptable to use brain cells or animal models? How should one handle patients’ data and cells? MODEM is actively considering these issues.

Furthermore, MODEM trains researchers in skills that can contribute to impact through a Graduate School.

Graduate School for impact

MODEM organises a Graduate School for PhD researchers (who carry out the bulk of the research): each year, there are several meetings in which they explore topics such as diagnostics, science communication and ethics together.

In this way, MODEM offers PhD researchers the opportunity to develop themselves outside the laboratory as well, and to explore what they can do to ensure that their findings ultimately do genuinely help people with dementia.

Together with stakeholders

A user committee has been set up within MODEM. Its members include people with dementia, doctors and researchers.

It has proved difficult to incorporate the involvement of people with dementia (and their carers), as the research is quite fundamental in nature and takes place mainly in the laboratory. Specialist knowledge is required to assess this.

MODEM does, however, have ideas for restructuring its collaboration with users in a follow-up project. MODEM then intends to continue working towards both the development and application of a medicine. In doing so, MODEM sees greater scope for a user committee to play a meaningful role.