Frontotemporal Dementia (FTD)

The primary objective of this clinical study is to provide the initial validation for monitoring biomarkers of symptoms and functioning for individuals with frontotemporal lobar degeneration (FTLD) syndromes. Researchers at BioSensics, Johns Hopkins University School of Medicine, and Massachusetts General Hospital will use wearable sensors, computerized speech, psychomotor, and cognitive assessments to create outcome measures and digital biomarkers for FTLD syndromes. Researchers will deploy this digital health solution to monitor 60 patients with FTLD syndromes for 24 months with study visits every 6 months.

The goal of this observational study is to learn if an artificial intelligence (AI)-based speech analysis tool can identify which patients with memory problems need specialist evaluation at a memory clinic. The main questions it aims to answer are: Can the AI model accurately distinguish between patients who need referral to a memory clinic (those with dementia or Mild Cognitive Impairment) and patients who don't (those with normal cognition or memory problems from other causes like depression)? Which speech patterns and cognitive test features are most useful for making this distinction? Researchers will compare speech recordings and cognitive test results from patients diagnosed with dementia or MCI to those from patients with normal cognition or non-neurodegenerative cognitive impairment to see if the AI model can reliably predict who needs specialist dementia care. Participants will: Complete standard cognitive tests at the memory clinic Perform structured speech tasks while being audio-recorded Receive their usual clinical evaluation and diagnosis from memory clinic specialists The results of this study will help develop a tool that can assist doctors in making faster, more accurate decisions about which patients need specialist dementia evaluation, potentially leading to earlier diagnosis and better patient outcomes.

The primary objective of this clinical study is to provide the initial validation for monitoring biomarkers of symptoms and functioning for individuals with FTLD syndromes. Researchers at BioSensics and Johns Hopkins School of Medicine will use wearable sensors, computerized speech, psychomotor, and cognitive assessments to create outcome measures and digital biomarkers for FTLD syndromes. Researchers will deploy this digital health solution to monitor 20 patients with FTLD syndromes for 12 months with study visits every 3 months.

The aim of the study is to evaluate the safety, feasibility, clinical and biological efficacy, and predictors of efficacy of an intervention consisting of transcranial alternating current stimulation (tACS) in patients with Frontotemporal Dementia (FTD). In addition to typical symptoms, FTD also present alterations in brain oscillations. In animal models of neurodegeneration, restoration of oscillations via neuronal "entrainment" phenomena has demonstrated a significant reduction in toxic protein accumulation, resulting in improved cognitive function. tACS is a neurophysiological noninvasive method of neuromodulation increasingly studied for its therapeutic potential. It has been shown to safely modulate the oscillatory frequencies underlying multiple cognitive functions, including verbal memory, perception, and working memory. In light of this evidence, it is proposed to apply a single-session treatment of β-tACS stimulation in patients with FTD and to evaluate its clinical effects, oscillatory modifications by EEG, and changes in neurophysiological indices such as short intracortical inhibition (SICI) and intracortical facilitation (ICF), both compromised in the disease. The study has a cross-over design (multicenter, randomized, placebo-controlled and double-blind), with FTD patients randomly assigned to one of the two arms: i) Group 1, who will receive a real tACS session first (1h); ii) Group 2, who will instead undergo a sham tACS session (1h). In the next phase (cross-over), one week after the first phase, the groups will reverse the treatment: Group 1 will receive tACS sham and Group 2 will receive real tACS. The main objectives of the study are: \[1\] to evaluate the safety and tolerability of the single tACS treatment session; \[2\] to investigate the effects of the protocol on (short-term) cognitive performance in patients with FTD; \[3\] to verify intervention-induced changes in brain synchronization; \[4\] to evaluate changes in neurophysiological indices following treatment; and \[5\] evaluate any predictors of efficacy.

Diagnosis of ALS/FTD disease spectrum is challenging because it largely relies on clinical symptoms. Identifying novel biomarkers is essential for a paradigm shift towards a more precise biological-based diagnosis. To achieve this aim, having access to proper specimens and analytical methods is crucial. Our team of experts in neurology, biology, chemistry, physics, and AI will explore ALS/FTD from novel perspectives using transcriptomics, proteomics, genomics and other innovative approaches to analyzing easily accessible tissues. The seed amplification assay (SAA) will be also exploited to detect pathological TDP-43. This project aims to create disease fingerprints useful for patient stratification and monitoring of disease progression, and to evaluate the therapeutic efficacy in clinical trials, thus overcoming the limits of clinical interpretation. Discovering new biomarkers and cellular pathways will improve the diagnosis and treatment of these devastating diseases.

The goal of this clinical trial is to learn if vortioxetine improves mood symptoms and cognition in patients with early-stage behavioral variant Frontotemporal Dementia (bvFTD). The main questions this study aims to answer are: 1. Do individuals with mood symptoms and bvFTD have brain changes and cognitive profiles that differ compared to individuals without bvFTD? 2. Do mood symptoms and cognition improve following treatment with vortioxetine? Researchers will also determine whether there are changes in the brain associated with vortioxetine treatment. Participants will: * Undergo a screening visit that involves clinical assessments and laboratory tests * Undergo an initial brain magnetic resonance imaging (MRI) and fluorodeoxyglucose (18F) Positron Emission Tomography (FDG PET) scan before starting treatment with vortioxetine * Undergo memory and problem-solving tests before starting treatment with vortioxetine * Undergo approximately 12 weeks of treatment with vortioxetine, during which time there will be regular contact and assessments with the study psychiatrist * Undergo a repeat PET scan and repeat memory and problem-solving tests after 12 weeks of treatment with vortioxetine

This is a longitudinal observational study recruiting individuals between the ages of 50 and 90 with different types of dementia as well as a comparison group without cognitive deficits. Participants are/will be recruited at sites across Canada and will undergo assessments, neuroimaging, and biological sample collection.

This clinical trial aims to evaluate the clinical efficacy and safety of Deep Cervical Lymphaticovenous Anastomosis (DLVA) in patients aged 50-80 with moderate to severe neurodegenerative dementia. Participants will undergo surgical treatment, followed by cognitive assessments, PET/MRI scans, lymph fluid/cerebrospinal fluid collection, and blood tests. Additionally, the study will perform an in-depth analysis of DLVA's therapeutic mechanisms using multimodal imaging and molecular biology experiments.

The goal of this clinical trial is to test whether we can reliably and safely measure the accumulation of pathological protein TDP-43 \[involved in rare forms of dementia such as frontotemporal dementia (FTD) and in amyotrophic lateral sclerosis (ALS)\] using a new positron emission tomography (PET) tracer called \[18F\]ACI-19626. Both healthy people and people with (suspected) TDP-43 accumulation will participate to this trial. The main questions it aims to answer are: * whether \[18F\]ACI-19626 is safe and well tolerated when injected into participants * whether \[18F\]ACI-19626 reliably detects abnormal TDP-43 in the brain using PET technique. * whether there are differences in the amount of this protein between people with diseases related to TDP-43 accumulation in the brain and people without these diseases. Participants will: * Visit the clinic to consent to their participation and to ensure they are eligible (physical and neurological examinations, questionnaires, blood and urine tests, ECG and MRI in some cases). * Visit the clinic to receive the tracer \[18F\]ACI-19626 intravenously and be scanned in a PET scanner, during which blood will be collected. * Receive a phone call from the clinic 2 to 4 days after the PET scan to report any symptoms and side-effects that they may be having. Some of the participants may be asked to come again to the clinic for a second PET scan, allowing the researchers to determine if the measurements with the first PET scan are stable and reproducible.

Neurodegenerative disorders (NDDs), such as Parkinson¿s disease (PD), Alzheimer¿s disease (AD), Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are characterized by aggregation and intracellular accumulation of misfolded proteins, which are believed to play a key role in synaptic dysfunction and neuronal death. Protein structural complexes in biofluids have been proposed to mirror pathological conditions suggesting their use as biomarkers for NDDs characterized by protein aggregation. In this framework, we plan to: i) collect a large cohort of NDD and prodromal patients and healthy subjects using standardized clinical and genetics procedures; ii) apply a novel method based on genomics, proteomics and bioinformatic analysis to map protein complexes in biofluids; iii) identify novel circulating biomarkers and correlate them to genetic profiling and disease endophenotypes, and; iv) validate the biological properties in human brain tissue and dopaminergic cultures.