Frontotemporal Lobar Degeneration

Difficulties with speech and language are the first and most notable symptoms of primary progressive aphasia (PPA). While there is evidence that demonstrates positive effects of speech-language treatment for individuals with PPA who only speak one language (monolinguals), there is a significant need for investigating the effects of treatment that is optimized for bilingual speakers with PPA. This stage 2 efficacy clinical trial seeks to establish the effects of culturally and linguistically tailored speech-language interventions administered to bilingual individuals with PPA. The overall aim of the intervention component of this study is to establish the relationships between the bilingual experience (e.g., how often each language is used, how "strong" each language is) and treatment response of bilinguals with PPA. Specifically, the investigators will evaluate the benefits of tailored speech-language intervention administered in both languages to bilingual individuals with PPA (60 individuals will be recruited). The investigators will conduct an assessment before treatment, after treatment and at two follow-ups (6 and 12-months post-treatment) in both languages. When possible, a structural scan of the brain (magnetic resonance image) will be collected before treatment in order to identify if brain regions implicated in bilingualism are associated with response to treatment. In addition to the intervention described herein, 30 bilingual individuals with PPA will be recruited to complete behavioral cognitive-linguistic testing and will not receive intervention. Results will provide important knowledge about the neural mechanisms of language re-learning and will address how specific characteristics of bilingualism influence cognitive reserve and linguistic resilience in PPA.

The investigators will compare \[18F\]-PI-2620 tau PET scans from patients with frontotemporal lobar degeneration (FTLD), patients with non-amnestic presentations of Alzheimer's disease (naAD), and demographically matched cognitively normal subjects.

Frontotemporal lobar degeneration (FTLD) is a clinically heterogeneous syndrome, characterized by progressive decline in behaviour and/or language. From a pathological standpoint, like the great majority of neurodegenerative disorders, FTLD are proteinopathies, which are characterized by the presence of specific protein deposits in the Central Nervous System (CNS). Accordingly, the two main deposits observed in FTLD are either made of Tau or transactive response DNA binding protein 43 (TDP-43). In pathological conditions such as FTLD, both proteins are aggregated and hyperphosphorylated. It is now well established that the pathological process in some proteinopathies such as synucleinopathies (of which Parkinson's disease is the main representative) is not limited to the brain but also widespread throughout the peripheral autonomic networks, including the autonomic innervation of the skin. In this context, many independent studies have shown that the pathological process in PD could be detected using routine punch skin biopsies opening the way for the development of original histopathological markers of the disease. Our hypothesis is that such a scenario could also occur in FTLDs and that the detection of the pathological tau or TDP-43 protein in the skin could help in diagnosing FTLD. This is especially relevant as, despite the recent progress in genetics, neurobiology and neuroimaging, there are no available biomarkers for FTLD.

MARKERS-NDD is a prospective, observational, longitudinal study, which aims to collect data from patients affected by neurodegenerative diseases (NDD) followed longitudinally for routine examinations performed as part of normal clinical practice. Data collected from clinical evaluations, movement analysis, brain imaging, neuropsychological and electroencephalographic assessments, blood chemistry tests will be analysed to carry out statistical investigations and predictive analyses, also using artificial intelligence systems, which allow the identification of new early markers of diagnosis and prognosis of neurodegenerative diseases.