Definition of new forms of the behavioural variant of frontotemporal degenerations (FTD)

Published May 5 2021
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Frontotemporal degeneration (FTD) is a complex neurodegenerative disorder that can manifest itself through a wide range of symptoms. Valérie Godefroy, postdoctoral researcher in the Frontlab, under the supervision of Lara Migliaccio, and her colleagues at the Paris Brain Institute and the Pitié-Salpêtrière Hospital are enriching the clinical picture of this pathology by identifying new subtypes of its behavioural variant. This more precise definition of the different forms of the disease is essential for more personalised management of patients. The results are published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring.

Frontotemporal degeneration (FTD) is a neurodegenerative disease that can manifest itself through a wide range of clinical signs, making its diagnosis complex. A major objective for clinicians working on this disease is to better characterise this diversity of forms of the disease and to identify subgroups with common characteristics. The challenge is to better understand every aspect of the disease and its progression in order to provide personalised care for patients.

One of the main symptoms of the behavioural variant of FTD is inhibition deficits, i.e. a generalised difficulty in controlling behaviour. This manifests itself in socially maladaptive behaviour (inappropriate thinking, disregard for social conventions, etc.), impulsivity and compulsive actions (repeating the same action or gesture several times automatically, for example). Based specifically on these behavioural manifestations of inhibition deficits, the study conducted by Valérie Godefroy and her colleagues at the Paris Brain Institute sought to identify subtypes of FTD patients.

Disinhibition behaviours are particularly difficult to assess and objectify, and do not necessarily present themselves in an obvious way during consultations with the doctor. One of the challenges of the study was therefore to measure these symptoms in detail, by observing them in a context close to real life, using what is called an “ecological approach”.

We took advantage of a protocol already in place at the Brain Institute as part of the ECOCAPTURE project, led by Bénédicte Batrancourt and Richard Levy, which includes time in the functional exploration room of the Institute’s PRISME platform. “explains Valérie Godefroy. This room was set up as a comfortable waiting room and presented as such to the 15 FTD patients and 15 control subjects included in the study. The participants spent about 45 minutes in the room, which was filmed and included time for discussion with an investigator. “This seemed to us to be an interesting situation for measuring uninhibited behaviour because it could generate impatience or even frustration in the participants, who did not know how long this waiting situation would last,” continues the researcher.
By analysing the behaviours observed in the video recordings, the researchers identified two main types of inhibition deficit: automatic compulsive behaviour and socially maladaptive behaviour. They then highlighted three behavioural groups of FTD patients, whose specificities (notably in terms of atrophied brain regions) were explored. The first group, very different from the other two, showed a lot of compulsive behaviour and very severe atrophy in the orbitofrontal regions and the ventromedial prefrontal cortex. “These data suggest that strong compulsive behaviours may be indicative of high disease severity. “says Valérie Godefroy.

The other two groups were less affected in their behaviour and differed from each other in socially inappropriate behaviour. Unexpectedly, the group with the most socially inappropriate behaviour was the group with the least atrophy in the brain. It was also characterised by more anxiety and depressive symptoms, potentially related to more awareness of the disease.

Taken together, these results allow us to enrich the clinical picture of FTD. We identify two main subtypes of the behavioural variant of this disease, associated with different brain damage. These data need to be supported by other studies, particularly longitudinal studies, i.e. with follow-up of patients over time, but they should make it possible to better stratify patients on the basis of their behaviour in order to offer them appropriate treatments. “concludes the researcher.