For World Health Day 2023, we caught up with Dr Maura Malpetti, to hear more about her research on frontotemporal dementia.
Sidney College Research Associate Dr Maura Malpetti grew up between Mantua and Verona, in northern Italy. Having completed her undergraduate and postgraduate studies in Milan, she came to Sidney in 2017 for her PhD.
Since 2022, Maura has been a Race Against Dementia and Alzheimer's Research UK Fellow, and is based at Addenbrooke’s Hospital in Cambridge where she is part of a wider team researching neurodegenerative diseases. Her specific interest is in frontotemporal dementia and Alzheimer's Disease.
What are the key differences between frontotemporal dementia and Alzheimer’s?
“So, when we speak about dementia, we speak about an umbrella of different syndromes and different ways of manifesting brain disorders. We use various labels to help with the management of patients, but sometimes the boundaries are not so clear.
“With Alzheimer’s, we normally see memory difficulties, while frontotemporal dementia mainly affects personality, behaviour and language. As the disease develops, we see other changes, but those are the early symptoms.
“Frontotemporal dementia also occurs a bit earlier than Alzheimer’s. It’s often first diagnosed in patients under 65 years old, so it can be very impactful, not just for the patient but for the entire family.”
So, I know you use a specific technique in your work. Can you explain what that is?
“Yes, it's called Positron Emission Tomography, or PET, and it involves a very powerful, specialised brain scan.
“Basically, you inject a dye into the patient’s blood and that dye then binds to specific proteins or biological targets in the brain. We can then see what is happening in the brains of living patients with dementia.
“If someone presents with symptoms of dementia, you need a brain scan to confirm the diagnosis, because sometimes there are other conditions which mimic dementia.
“We can also sometimes use this scan to confirm the type of dementia, based on the region of the brain involved or the presence of different junk proteins.
“For my PhD, I also looked at the role of brain scans in prognosis, and I have continued that work beyond my PhD. So, I am using brain scans to measure brain changes in people with dementia, and trying to identify which features can tell us who will decline faster in the future based on what we can see now.
“I am also looking at how the brain immune system is functioning in people with dementia and how brain inflammation relates to their dementia and to their symptoms. This has implications for treatment. We can see, for example, that greater inflammation in the brain and a chronically overactive immune system is related to much faster decline over time. This opens up the possibility that if we can switch off the right part of the immune system in these people, we can perhaps stop, or slow, their decline.
“And, of course, the future is also about early detection and prevention. So, once we have identified which scans and specific brain changes are important, we would like to move to scanning people earlier in life, because the changes we are talking about actually start decades before the symptoms.
“In addition to the scans, we are looking to develop blood tests, to identify patients with high and specific patterns of brain inflammation. A blood test would mean that we can reach a far wider group than we can currently with the scans.”
Is the immune system response you describe, the inflammation, is that a long-established link with dementia?
“It is more recent - the link to junk proteins has been more studied - but in the last few years there has been a boom in evidence of links to the immune system.
“These studies have been around for many years, but mainly in animals or where people have donated their brains. We now have techniques to look at this in living patients and so we can identify much more information that way.
“The thing that causes the decline itself - the decline in cognitive performance - is that the cells die, and also that they stop communicating with one another before dying.
“But the problem we are trying to understand is why these cells die and it seems that inflammation damages the communication between cells, together with junk proteins.
“There's still a debate about what happens first. Is there inflammation which results in an accumulation of these junk proteins? Or is there an accumulation of junk proteins that leads to a dysfunctional immune system?
“I think that, in the future, we will need drugs that target inflammation and junk proteins together."
It sounds like a very busy time. For those who would like an insight into what it means to be a medical researcher, what is your day-to-day like?
(Laughs) “Well, I'm not doing what people maybe think of when they think about what it means to work in a lab. I'm not pipetting! I'm far more on the patient-facing side. I meet the patients that come to our clinics here in Cambridge, and we ask them if they want to be part of our research.
“We enrol them, and then I collect data through the brain scans. I analyse that data, to basically make sense of what the scans produce, and then we look at that data alongside the results of their blood tests and thinking/memory performance, for example.
“I am part of a bigger team which works on frontotemporal dementia. Within that team we have psychologists, neuroscientists, biologists, medical doctors, nurses, engineers who help with the data collection and analysis… There are people who use other types of brain scans, and people who test patients in more conventional ways, to see how their symptoms change over time.
“No one person can do everything - it's a big team, and a very strong collaboration.”
Dr Maura Malpetti is a member of the Centre for Frontotemporal Dementia and Related Disorders and the Department of Clinical Neurosciences.
You can find more information on the work of Race Against Dementia and Alzheimer's Research UK on their websites.
If you have something that would make a good news or feature item, please email news@sid.cam.ac.uk