Clinical Research Directory

ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD)

ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) represents the formalized integration of ARTFL (U54 NS092089; funded through 2019) and LEFFTDS (U01 AG045390; funded through 2019) as a single North American research consortium to study FTLD for 2019 and beyond.

Assessment of Apathy in a Real-life Situation, With a Video and Sensors-based System

Apathy is defined as a quantitative reduction in voluntary and goal-directed behavior. To address this, the investigators propose an ethological approach to assess apathy objectively and quantitatively by observing patients in real-life situations. The ECOCAPTURE paradigm involves a structured, multi-step scenario conducted in a functional exploration platform. This platform is equipped with an advanced data acquisition system integrating video recordings and sensors to precisely monitor and analyze participants' behavior. Primary objective: Develop a diagnostic tool for apathy using metrics derived from video recordings and sensor data. This tool aims to provide objective measures to identify and quantify apathy. Secondary Objectives: * Validation of ICM\_APATHY\_TASKS: This novel experimental task is designed to evaluate three primary mechanisms thought to underlie apathy: Motivation, Cognitive inertia (difficulty initiating tasks), The interaction between motivation and action execution. * Identification of the pathophysiological mechanisms of apathy by investigate the cognitive, behavioral, neural, and neurohormonal underpinnings of apathy. This will enable the classification of apathetic patients into subtypes (or several forms of apathy) based on the dominant mechanisms and provide insights into which processes best explain apathy in individual cases. This innovative framework aims to deepen the understanding of apathy, improve diagnostic precision, and pave the way for tailored interventions.

Tracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases

Neurodegenerative diseases, including frontotemporal lobar degeneration (FTLD) spectrum syndromes, are characterized by the accumulation of insoluble protein aggregates in the central nervous system. A common feature of these diseases is that pathological changes accumulate over time following a stereotyped spatial pattern, which contributes to the onset and progression of clinical symptoms. Until recently, the causes of such progression were still unknown. Recent pathological and neuroimaging studies have, however, suggested that insoluble and pathological protein aggregates are able to alter the conformation of neighboring proteins and spread through cell-to-cell transmission. According to this theory, called the 'brain connectome,' the brain network is established as a set of nodes, which correspond to different anatomical regions. These brain networks are highly connected to each other and their internal organization is fundamental for an efficient integration of information coming from different regions and to guarantee adequate levels of motor/cognitive performance. Thanks to magnetic resonance studies and research in the field of brain networks, it is possible to understand the pathophysiology of neurodegenerative diseases and reveal the connectivity profiles associated with different clinical outcomes. The main objective of this project is to explore the mechanisms of neurodegeneration associated with the different FTLD spectrum syndromes, and in particular the hypothesis that the neurodegenerative process is driven by the structural architecture of the brain 'connectome'. The ultimate goal is to apply mathematical models to structural and functional connectivity data to predict the evolution of the neurodegenerative process in sporadic and genetic forms of Frontotemporal Lobar Degeneration Disease. This study aims to investigate the spatiotemporal progression of neurodegeneration in frontotemporal lobar degeneration (FTLD) using advanced neuroimaging and connectomics. 360 patients with sporadic FTLD (including bvFTD, semantic and nonfluent PPA, PSPs, CBS, and ALS) and 65 patients with genetic FTLD (MAPT, GRN, and C9orf72 mutati will be enrolled. The study also plans to enroll 120 subjects who are members of families carrying FLTD-associated mutations (including 60 mutation carriers). Finally, 100 healthy controls will also be enrolled, including 50 young healthy controls and 50 healthy controls comparable with patients by sex and age. Participants will undergo clinical, neuropsychological, and behavioral assessments, blood and Cerebrospinal fluid (CSF) collection, and multimodal 3Tesla Magnetic Resonance Imaging MRI at baseline and every 6 months for up to 2 years. Primary objectives include mapping longitudinal changes in structural and functional brain networks, developing predictive models of network degeneration and clinical decline, and characterizing protein-specific patterns of network degeneration. Secondary aims include identifying early network biomarkers in presymptomatic carriers and correlating network changes with biological markers.

Neuroinflammation in FTLD

The goal of this observational study is to investigate the role of neuroinflammation in frontotemporal lobar degeneration (FTLD). The main aims of this study are: 1. To elucidate the role and timing of neuroinflammation in FTLD by using a combination of clinical measures, 7T MRI, and CSF biomarkers; 2. To differentiate FTLD-TDP and FTLD-tau during life using biomarkers for neuroinflammation; 3. To identify biomarkers to predict and monitor disease progression in FTLD; Secondary aim: 1\. To explore the role of brain clearance in the disease process of FTLD. Participants will undergo 7T MRI scans, blood and CSF collection, clinical, neurological, and neuropsychological evaluation.