A name, a familiar face, a holiday many years ago: personal memories do not originate in a single part of the brain. Many regions work together as a network. In Alzheimer’s disease, this interaction becomes increasingly out of sync. A recent review article by Prof. Emrah Düzel, Director of the Institute for Cognitive Neurology and Dementia Research at Magdeburg University Hospital, and Prof. Dr Michael R. Kreutz, Head of the Neuroplasticity Research Group at the Leibniz Institute for Neurobiology in Magdeburg, offers a new perspective on the disease: not all memory problems can be explained solely by the loss of nerve cells. What role do the brain’s networks play, and what does this mean for treatment? We spoke to Prof. Düzel about this.
Prof. Düzel, can people with Alzheimer’s actually recover lost memories?
We need to make a clear distinction here. If nerve cells and their connections have been irretrievably lost, we cannot reverse this damage with current methods. But Alzheimer’s is more than just the loss of nerve cells. Even before that happens, the functioning of synapses and brain networks may already be impaired. The resources may still be present, but they are no longer being used to their full potential. This is precisely where a possible point of intervention lies; in principle, therefore, some aspects of memory function could be influenced.
Does this change our current understanding of Alzheimer’s?
For a long time, we have viewed Alzheimer’s very much through the lens of loss: nerve cells die off, connections are lost. This remains central. At the same time, however, we must also ask: what is still there, and how can it be used to its full potential?
To understand this, it is important to realise that our memory does not function like a single storage unit. For personal experiences – what is known as episodic memory – the hippocampus and many other regions of the brain work together. In Alzheimer’s, this network becomes unbalanced. Some areas are underactive, whilst others may be overactive. The brain also tries to compensate for these deficits.
You call this approach the ‘Circuit Utilisation Framework’. What is the thinking behind it?
Essentially, it comes down to a simple question: how effectively does the brain utilise what is still available to it? We view memory as the interaction of various neural circuits and investigate how their utilisation changes in Alzheimer’s disease.
If we understand which circuits are still functioning and where their coordination is disrupted, we can intervene in a more targeted way – for example, through cognitive or physical training, non-invasive brain stimulation or targeted medication. This isn’t simply about ‘brain training’, but about identifying which processes and circuits are actually influenced by such training. These approaches are intended to complement, not replace, the treatment of the underlying causes of the disease.
Why do some people cope surprisingly well with changes in the brain for a long time, whilst others do not?
This is one of the major questions in neuroscience. People with comparable Alzheimer’s pathology can develop very different cognitive symptoms. One reason may be what is known as ‘cognitive reserve’: the brain’s ability to use resources flexibly and switch to other networks. This is precisely where our collaborative research center ‘Neural Resources of Cognition"’ (SFB 1436) comes in, in which we investigate how the brain maintains its cognitive performance. Particularly fascinating in this context are so-called ‘super-agers"’, whose memory performance is on a par with that of significantly younger people. If we understand their resources, we might also understand why some people experience virtually no symptoms for a long time, despite changes typical of Alzheimer’s.
So, could we learn from super-agers how to make the brain more resilient?
That is precisely what we are investigating. We are finding evidence of special characteristics in certain memory structures among them. This shows us that the brain can possess astonishing resources even in old age. The task now is to find out which of these are biologically determined and which can be influenced.
How do you determine which resources are still available in a person’s brain?
This requires precise diagnostics that begin as early as possible, as Alzheimer’s begins long before pronounced dementia sets in. Modern imaging helps us with this. It shows us not only how regions of the brain are structured, but also how they function and communicate with one another. Magdeburg offers a unique combination of clinical expertise, basic neuroscientific research and state-of-the-art technology – ranging from a 7-tesla MRI and PET-MRI to modern techniques that allow us to examine the brain’s connectivity and function in great detail. The key factor, however, is the close collaboration between the university, the university hospital, the German Centre for Neurodegenerative Diseases and the Leibniz Institute for Neurobiology, all located on the same campus.
How far are we from turning this research approach into a treatment?
We are only just beginning. Our review article provides a scientific framework. Some of the techniques discussed are already being investigated in clinical trials, but a widely available therapy cannot yet be derived from this. It remains to be seen which intervention is suitable for whom, when it should be used, and which neural circuits are actually affected in the process.
What could this approach mean in the long term for people with Alzheimer’s?
Our work does not promise a cure. However, it changes the way we view the disease and bases future Alzheimer’s therapy on two pillars: slowing down the disease process whilst simultaneously providing targeted support for the brain’s remaining resources. After all, for those affected, it is not just how they perform in a memory test that matters. What matters is whether they can still remember important people, cope with everyday life and live independently for as long as possible. Whether this can actually help them partially regain lost memory functions remains to be seen in future clinical trials.
