Who are the partners in this initiative?

Ten Dutch and two American research organisations and civil society organisations are collaborating within YOD-MOLECULAR.

The consortium is part of the KIC – Living with Dementia Programme funded by NWO.

Who’s who?

The Alzheimercentrum Amsterdam is the coordinator of YOD-MOLECULAR. Prof. Dr Yolande Pijnenburg (Alzheimercentrum Amsterdam) is the Principal Investigator and leads the consortium.

The research is divided into four so-called work packages. Yolande Pijnenburg leads one of these. Dr Laura Jonkman (Amsterdam UMC), Prof. Guus Smit (VU Amsterdam) and Dr Stefan Leijnen (Utrecht University of Applied Sciences) are each responsible for one of the other work packages (you can read more about these under ‘What kind of research?’).

Collaborating partners

• Alzheimercentrum Amsterdam, lead applicant
• Vrije Universiteit Amsterdam
• Utrecht University of Applied Sciences
• University of Groningen
• Erasmus MC
• Team Alzheimer
• Alzheimer Nederland
• FTD Peer Support Group
• Knowledge Centre for Young Onset Dementia
• The Brain Foundation
• Cambridge Cognition (United States)
• ALLEO Labs (United States)

YOD-MOLECULAR’s collaboration partners have in-house specialists in the fields of implementation and data organisation; therefore, no external organisations are involved in these areas. However, YOD-MOLECULAR does regularly collaborate with the Knowledge Centre for Young Onset Dementia on implementation and communication; see ‘Parties involved’.

See Nwo.nl for more information about the KIC-programma voor leven met dementie.

Early-onset dementia: what goes wrong? And how can you spot the signs sooner?

Very little is yet known about dementia in young people (under the age of 65). Diagnosis is also difficult and often comes too late. This is because dementia in young people often begins differently to that in older people. YOD-MOLECULAR explores four topics related to this; these are the consortium’s work packages.

Diagnosis: how can it be improved and, therefore, made earlier?

Most people associate dementia with memory problems. But in young people with dementia, it often starts very differently: with behavioural changes, language problems or, for example, difficulties with perception. Current dementia tests are not designed to detect these symptoms. As a result, the diagnosis is often made far too late. And that’s a shame: early intervention can make a huge difference to the person themselves and those around them. That is why YOD-MOLECULAR is working on new diagnostic tests as part of this work package.

Where in the brain does it go wrong?

Every form of dementia leaves its own traces of damage in the brain. In early-onset dementia, this also occurs differently to how it does in older people. The damage begins in different, often unexpected, areas. Furthermore, one area of the brain is often already affected, whilst other parts are still functioning perfectly well. What makes these damaged areas so vulnerable? YOD-MOLECULAR is delving into this question and investigating where things go wrong in the brain.

What makes brain cells more vulnerable?

Even within a damaged area of the brain, there are differences: one type of brain cell holds out, whilst another gives way. But why? What makes one brain cell vulnerable and another resilient? Which cells are these, exactly? And what goes wrong, inside the cell, at a molecular level? YOD-MOLECULAR examines each cell individually, right down to the smallest details. In this way, the researchers hope to find new leads for medicines.

What forms are there?

There are various forms of early-onset dementia. In some cases, behavioural changes or social problems are the main symptoms. For others, it is language problems or difficulties with vision. But exactly how many different forms are there? What do we know about these differences? And do we understand these forms well enough? YOD-MOLECULAR is gathering answers to these questions to gain a better understanding of early-onset dementia.

Curious about the concrete results of this research? Then read ‘What are the benefits?’.

Basic and clinical research

YOD-MOLECULAR conducts fundamental and clinical research into early-onset dementia. In collaboration with clinical practice.

YOD-MOLECULAR combines methods such as questionnaires, brain scans and cell research. The consortium uses artificial intelligence (AI) to bring this data together. In doing so, researchers work closely with people with first-hand experience: those with early-onset dementia, their loved ones and healthcare professionals.

Developing diagnostic tests

YOD-MOLECULAR is working on what is known as a digital test battery. This is a series of diagnostic tests and questionnaires designed to measure social skills. Examples include understanding what others are thinking or feeling, and recognising facial expressions and emotions. The researchers are conducting this clinical research on people with different types of dementia and on healthy individuals. In this way, they are determining the best way to diagnose early-onset dementia. They are also discussing with young people with dementia (and their loved ones) which tests are the clearest and most comfortable to take.

Detecting language changes with AI

The team is also working on an automated language analysis tool to quickly detect subtle changes in language. This aids diagnosis. To this end, YOD-MOLECULAR researchers are making short audio recordings of conversations with young people with dementia. Using AI algorithms, researchers analyse aspects such as word choice, sentence structure and speech rate from this clinical study.

The consortium is also testing the battery of tests and the language analysis tool in memory clinics to see if they work effectively. In doing so, they are comparing, for example, test results from people with early-onset dementia with those of people with mild memory problems or other memory difficulties.

MRI scans and post-mortem examinations

To understand what is happening in the brains of young people with dementia, researchers carry out MRI scans of the brain and post-mortem pathological examinations. This fundamental research reveals where in the brain the disease begins and how it spreads further.

Proteomics: measuring proteins

YOD-MOLECULAR also examines cells and substances (molecules) in the brain tissue of young people with dementia who have died, to discover more about what happens in the areas of the brain that are affected first. Using a specialised technique (proteomics), they can measure thousands of proteins simultaneously. They do this for each brain region, enabling them to identify the specific changes occurring in each one.
They are also examining the activity of individual cells. Using genetic techniques, they are investigating which processes are disrupted in vulnerable cells. For example, do these cells produce fewer protective proteins? Or, conversely, more stress-inducing substances?

From data to model via AI

All the data from the tests, scans and cell studies are combined into models using AI. These AI models process different types of data simultaneously, enabling researchers to identify links between observable characteristics in real-world settings (such as behaviour or language) and specific brain changes and molecular processes.

Diagnostic tests, language analysis and insights

YOD-MOLECULAR develops knowledge products that help to better understand and detect early-onset dementia.

These knowledge products are primarily intended for other researchers and doctors. However, their aim is to provide better and more personalised care for young people with dementia.

The project is still in full swing and the researchers are working hard to develop these tools. Only practical experience will tell whether everything turns out as hoped.

Diagnostic test battery

YOD-MOLECULAR is working on a collection of diagnostic tests (known as a ‘test battery’) to make it easier to diagnose dementia in young people. The tests are available online, are quick to complete and are easy to use. Doctors can use these tests.

Language analysis tool

Another practical tool is a language analysis tool. Based on a short speech recording, it can check for signs of language problems associated with certain forms of early-onset dementia. Such a tool helps doctors to recognise changes in language in someone with early-onset dementia.

Scientific publications

In addition, YOD-MOLECULAR publishes scientific articles on exactly what happens in the brains of young people with dementia. These include articles on new markers that can be used to identify certain types of early-onset dementia, for example, or on where the damage begins and how it spreads. This knowledge helps other researchers to guide their own research. It also helps doctors to better understand whether someone has dementia and what the course of the disease might look like.

For more publications, visit zonmw.nl.

In collaboration with the target group and patient organisations

YOD-MOLECULAR actively involves young people with dementia (and their loved ones) in the research. This is done through a panel of people with lived experience and a research group (cohort), set up by fellow researchers from YOD-INCLUDED.

Experts by experience have a say

The panel contributes ideas to the research. For example, regarding diagnostic tests. Researchers also ask them for feedback: how are certain tests perceived? Does this work for young people with dementia and their loved ones, or does it actually ask too much?

Awareness and communication

YOD-MOLECULAR also works with patient organisations, such as Alzheimer Nederland, the Knowledge Centre for Young Onset Dementia and FTD Lotgenoten, to raise awareness and improve communication. Together, they ensure that information about early-onset dementia is easier to find. Through social media, short videos and apps, they provide young people with dementia and their families with information in an accessible way.