DESCRIBE-FTD · DElineation of Striato-CoRtical contrIbutions to BEhavioral symptoms in FrontoTemporal Dementia

DElineation of Striato-CoRtical contrIbutions to BEhavioral symptoms in FrontoTemporal Dementia

Background Second to Alzheimer’s disease (AD) in prevalence, frontotemporal dementia (FTD) is a neurodegenerative condition resulting from the progressive deterioration of the frontal and temporal lobes of the brain. Cognitive and behavioural impairments are the most early and prevalent characteristic of FTD. Aims In this project, our goal was to characterize and contrast the integrity of the striatal subregions in FTD and AD and in healthy aged controls using structural neuroimaging to delineate striatal and cortical contributions to behaviour in FTD. A second goal was to enhance the characterization of frontal related cognitive processes and their interactions of domains such as social cognition, executive functioning and memory, all key domains in the clinical distinction between FTD and AD. Results Regarding the first goal, using structural neuroimaging relying on voxel based morphometry, we observed a substantial striatal atrophy in FTD comparatively to control participants, affecting the regions of the striatum that are connected to ventral and anterior/posterior dorsal frontal regions. Comparatively with AD, who only presented a mild atrophy of striatal regions connected to posterior frontal regions, we observed that FTD is characterized by a severe atrophy of ventral striatal regions that are connected to the ventro-median prefrontal cortex (Bertoux et al., 2015). Extending these results, we studied correlations between behavioural symptomatology (as measured by the Cambridge Behavioural Inventory) and the fronto-striatal integrity. We observed that both prefrontal and striatal regions were predictors of behavioural symptoms, with the former having the main influence despite the significant role of the ventral striatum (Bertoux et al., in preparation). Concerning the second goal, we conducted a data-driven study using automated classifications procedures aiming to study the relationship between theory of mind (ToM, the ability to infer what others think or feel) which is a critical aspect of social cognition and executive dysfunctions (such as attention and working memory) that are involved in many aspects of cognition. We observed, in FTD, a relative independence of ToM with executive functions but a significant link between in intention inference and empathy dimensions of ToM, suggesting a complex link (Bertoux et al., 2016). In AD, this relationship was no more independent as executive dysfunctions (and not memory impairment) were the main contributor of ToM impairment, suggesting that ToM impairment in AD are not genuine and caused by a general cognitive decline (Bertoux et al., in review). Taken together, this suggest that current ToM clinical assessment cannot delineate executive and ToM dysfunctions and that some critical components of ToM are currently not evaluated in clinical assessments of social cognition. We thus developed a novel experimental task assessing such dimensions, such as social context and social rules processing, and piloted this task on patients with acquired lesion of the ventromedian prefrontal cortex. Results indicated that frontal regions were not involved in the processing of both cognitive processes, suggesting that the atrophy of temporal and not frontal regions in FTD is causing these impairments (Bertoux et al., in preparation). Finally, in order to explore the ability of social cognition assessment to discriminate FTD and AD regarding of the presence of amnesia, we performed a retrospective study contrasting amnestic FTD and non-amnestic FTD with AD. In that purpose, the discriminative power of the reduced Social cognition & Emotional Assessment (mini-SEA) was 85 and 94% respectively, thus confirming the usefulness of social cognition to clinically identify and diagnose FTD (Bertoux et al., 2015). Conclusion Through this project, we confirmed that the atrophy of the striatum is characteristic of FTD, related to clinically observable symptoms and thus could be employed as a new neuro-radiological marker of FTD for diagnosis purpose. In addition, we demonstrated the usefulness of social cognition to discriminate FTD from AD and documented the complex relationship between ToM and executive functioning, pleading for the necessity to develop new and more comprehensive way to assess social cognition, which we started to do at the end of this project. Socio-economic impact Beside a great impact of the results in the scientific community, we have significantly impacted the clinical procedures for the diagnosis of FTD, highlighting the usefulness of social cognition assessment to discriminate this disease from AD. We aim that these results will lead to a decrease of misdiagnosis among this clinical population. Gender equality actions Gender balance in the mentioned studies was strictly maintained but no other specific actions were used. Ethical issues All aspects of the proposal were covered through Ethics (NHS 15/LO/0123 & 16/LO/1366) and all patients were seen in accordance with the declaration of Helsinki for well practice in research.

Data: CORDIS, © European Union