Frontotemporal Dementia

This study is testing a new treatment for Frontotemporal Dementia (FTD) - a progressive brain disease that affects personality, behavior, and language. Currently, there is no cure for FTD and no approved medication that can slow down or stop the disease. Existing treatments only help manage some symptoms temporarily. The investigational treatment in this study is made from exosomes - tiny particles naturally released by umbilical cord stem cells. Exosomes act like "message carriers" between cells. Researchers believe they may help protect brain cells, reduce harmful protein buildup, and improve brain function. The exosomes will be given as a nasal spray (sprayed into the nose). This method may allow the treatment to reach the brain directly without needing to pass through the blood-brain barrier (a natural protective layer that often blocks medications from entering the brain).

Background: Neurodegenerative disorders can lead to problems in movement or memory. Some can cause abnormal proteins to build up in brain cells. Researchers want to understand whether these diseases have related causes or risk factors. Objective: To test people with movement or thinking and memory problems to see if they are eligible for research studies. Eligibility: People ages 18 and older with a neurodegenerative disorder associated with accumulation of TDP-43 or Tau proteins Design: Participants will have a screening visit. This may take place over 2-3 days. Tests include: Medical history Physical exam Questions about behavior and mood Tests of memory, attention, concentration, and thinking Movement measurement. The speed at which participants can stand up from a chair, tap their finger and foot, and walk a short distance will be measured. Some movements will be videotaped. They will be videotaped while they speak and read a paragraph. Blood tests. This might include genetic testing. Lung and breathing tests MRI. They will lie on a table that slides into a cylinder that takes pictures of the body. Some participants will get a dye through IV. Electromyography. A thin needle will be inserted into the muscles to measure electrical signals. Nerve tests. Small electrodes on the skin record muscle and nerve activity. A small piece of skin may be removed. A skin or blood sample may be taken to create stem cells. Optional lumbar puncture. A needle will be inserted into the space between the bones of the back to collect fluid. If participants are not eligible for current studies, they may be contacted in the future.

This is a human clinical study involving the isolation of autologous bone marrow derived stem cells (BMSC) and transfer to the vascular system and inferior 1/3 of the nasal passages in order to determine if such a treatment will provide improvement in neurologic function for patients with certain neurologic conditions. http://mdstemcells.com/nest/

This study is testing a new treatment for Frontotemporal Dementia (FTD) - a progressive brain disease that affects personality, behavior, and language. Currently, there is no cure for FTD and no approved medication that can slow down or stop the disease. Existing treatments only help manage some symptoms temporarily. The investigational treatment in this study is made from exosomes - tiny particles naturally released by umbilical cord stem cells. Exosomes act like "message carriers" between cells. Researchers believe they may help protect brain cells, reduce harmful protein buildup, and improve brain function. The exosomes will be given as a nasal spray (sprayed into the nose). This method may allow the treatment to reach the brain directly without needing to pass through the blood-brain barrier (a natural protective layer that often blocks medications from entering the brain).

GENFI Lille is a French cohort that belongs to the international initiative GENFI2, a five year longitudinal biomarker cohort study of genetic FTD and its associated disorders (including MND/ALS) investigating members of families with a known mutation in GRN or MAPT or an expansion in C9orf72 (including those affected with the disorder as well as at-risk members of families).

Metabolic and hormonal deregulations are both a risk factor and a hallmark of Alzheimer's disease (AD) and frontotemporal dementia (FTD), occurring early in the course of the disease. In FTD in particular, hyperorality and dietary changes are associated with metabolic and hormonal changes such as altered levels of the anorexigenic hormone leptin. The hypothalamus is a brain region that controls metabolism and hormonal systems. Hypothalamic function depends on its ability to sense peripheral signals. The hypothalamus sits on a circumventricular organ called the median eminence (ME) that puts it in contact with systemic blood circulation. In the ME, fenestrated capillaries allow the diffusion of bloodborne factors. However, despite the lack of blood-brain barrier at brain microvessels, diffusion is controlled by specialized ependymoglial cells, the tanycytes, which exert a barrier function between the ME and the third ventricle and controls the access of blood-borne molecules into the hypothalamus. Previous work from our laboratory and the ERC consortium has highlighted the role of tanycytes not only in the regulation of the release of neurohormones from neuroendocrine nerve terminals into the pituitary portal blood circulation, but also in the transport of circulating leptin into the hypothalamus. Hence hypothalamic dysfunction in AD and FTD can result either from dysregulation of neuroendocrine secretions, direct neuronal loss or from defective transport (and hence resistance) to hormones like leptin. This study is to demonstrate that leptin transport though tanycytes is early altered in FTD and AD and correlates

Hyperspectral retinal imaging is a non-invasive imaging modality in which a series of images of the retina are captured using light of different wavelengths. The resulting "hypercube" of data provides a wealth of information about the retinal structure. Our group has developed evidence supporting a role for this technology in the detection of retinal amyloid beta in Alzheimer's disease. We are undertaking further studies to establish the role of this method in the assessment of people with dementia, or those at risk of Alzheimer's disease. In addition, we wish to test whether the approach may have value in other forms of dementia or neurodegenerative disease such as Parkinson's disease, Lewy-Body dementia or vascular dementia.

The goal of this clinical study is to learn about an investigational gene therapy product called AVB-101, which is designed to treat a disease called Frontotemporal Dementia with Progranulin Mutations (FTD-GRN). FTD-GRN is an early-onset form of dementia, a progressive brain disorder that affects behavior, language and movement. These symptoms result from below normal levels of a protein called progranulin (PGRN) in the brain, which leads to the death of nerve cells (neurons), affecting the brain's ability to function. The main questions that the study aims to answer are: 1. Is a one-time treatment with AVB-101 safe for patients with FTD-GRN? 2. Does a one-time treatment with AVB-101 restore PGRN levels to at least normal levels? 3. Could AVB-101 work as a treatment to slow down or stop progression of FTD-GRN? In this study there is no placebo (a dummy pill or treatment used for comparison purposes), so all participants will receive a one-time treatment of AVB-101 delivered directly to the brain, with follow-up assessments for 5 years.

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 study aims to develop and evaluate biomarkers using non-invasive optical coherence tomography (OCT) and OCT angiography (OCTA) as well as ultra-widefield (UWF) fundus photography to assess the structure and function of the retinal and choroidal microvasculature and structure in persons with mild cognitive impairment (MCI) and Alzheimer's Disease (AD), Parkinson's Disease (PD), or other neurodegenerative disease, diseases as outlined.

To develop a model to predict disease progression in a large cohort of patients across a variety of neurodegenerative diseases, including Mild Cognitive Impairment (MCI) and dementia due to any neurodegenerative disease, including Alzheimer's Disease (AD), Lewy Body Disease (LBD), Vascular Disease (VaD) and Frontotemporal lobar degeneration (FTLD).

The purpose of this nationwide study is to test STELLA-FTD (Support via Telehealth: Living and Learning with Advancing Alzheimer's Disease)-FTD, an intervention to specifically address the needs of family Care Partners of persons with frontotemporal degeneration (FTD). STELLA-FTD is a multicomponent videoconference-based intervention designed to facilitate effective use of community and peer resources to foster effective management of behavioral and psychological symptoms of dementia. The study is recruiting families from across the United States.

Double blinded, sham-controlled, randomized trial on repeated transcranial alternating current brain stimulation (tACS) in neurodegenerative diseases. The investigators will evaluate whether a 4-times daily repeated stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with neurodegenerative diseases, including dementia with Lewy Bodies, Alzheimer's disease, idiopathic normal pressure hydrocephalus and Frontotemporal dementia.

Given the expansion of indications for genetic testing and our understanding of conditions for which the results change medical management, it is imperative to consider novel ways to deliver care beyond the traditional genetic counseling visit, which are both amenable to large-scale implementation and sustainable. The investigators propose an entirely new approach for the implementation of genomic medicine, supported by the leadership of Penn Medicine, investigating the use of non-geneticist clinician and patient nudges in the delivery of genomic medicine through a pragmatic randomized clinical trial, addressing NHGRI priorities. Our application is highly conceptually and technically innovative, building upon expertise and infrastructure already in place. Innovative qualities of our proposal include: 1) Cutting edge EHR infrastructure already built to support genomic medicine (e.g., partnering with multiple commercial genetic testing laboratories for direct test ordering and results reporting in the EHR); 2) Automated EHR-based direct ordering or referring by specialist clinicians (i.e., use of replicable modules that enable specialist clinicians to order genetic testing through Epic Smartsets, including all needed components, such as populated gene lists, smartphrases, genetic testing, informational websites and acknowledgement e-forms for patient signature); 3) EHR algorithms for accurate patient identification (i.e., electronic phenotype algorithms to identify eligible patients, none of which currently have phenotype algorithms present in PheKB; 4) Behavioral economics-informed implementation science methods: This trial will be the first to evaluate implementation strategies informed by behavioral economics, directed at clinicians and/or patients, for increasing the use of genetic testing; further it will be the first study in this area to test two forms of defaults as a potential local adaptation to facilitate implementation (ordering vs. referring); and 5) Dissemination: In addition to standard dissemination modalities,PheKB95, GitHub and Epic Community Library, the investigators propose to disseminate via AnVIL (NHGRI's Genomic Data Science Analysis, Visualization, and Informatics Lab-Space). Our results will represent an entirely new paradigm for the provision of genomic medicine for patients in whom the results of genetic testing change medical management.

The investigators are researching families with inherited inclusion body myopathy (IBM) and/or Paget disease of bone (PDB) and/or dementia (FTD) which is also called IBMPFD. IBMPFD is caused by mutations in the VCP gene. Our main goal is to understand how changes in the VCP gene cause the muscle, bone and cognitive problems associated with the disease. The investigators are collecting biological specimen such as blood and urine samples, family and medical histories, questionnaire data of patients with a personal or family history of VCP associated disease. Participants do not need to have all symptoms listed above in order to qualify. A select group of participants may be invited to travel to University of California, Irvine for a two day program of local procedures such as an MRI and bone scan. Samples are coded to maintain confidentiality. Travel is not necessary except for families invited for additional testing.

This is a first in human study that will assess the safety and diagnostic performance of \[18F\]RP-115 (fluorine-18 labeled RP115), a positron emission tomography (PET) agent. This agent has the potential to identify the early changes that occur in the brains of patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD).

The primary goal of this study is to test the hypothesis that oral nabilone treatment will reduce agitation compared with placebo in patients with Frontotemporal Dementia (both behavioural variant frontotemporal dementia and primary progressive aphasia). The study population is defined as patients with probable Frontotemporal Dementia that meet the International Psychogeriatric Association criteria for agitation in cognitive disorders.

This is an international multi-centre cohort study of first and second degree family members of individuals who carry Frontotemporal Dementia (FTD) mutations in MAPT, GRN or C9ORF72 repeat expansions for youths between the ages 9-17.

Neuroinflammation is increasingly implicated as a potential critical pathogenic mechanism in a variety of neurologic and psychiatric disorders. This study will use hybrid PET/MRI imaging to evaluate neuroinflammation and its relationship to cerebral perfusion in frontotemporal dementia (FTD). Patients with FTD will be recruited from the Cognitive Neurology and Aging Brain clinics at Parkwood Institute and will undergo neurocognitive assessment and MRI/PET using the PET ligand FEPPA which binds to activated microglia, a marker of neuroinflammation. Correlations will be conducted to determine whether abnormal neuroinflammation is present in Frontotemporal dementia and whether differential patterns of neuroinflammation are present in different FTD clinical and molecular subtypes, and to determine the relationship between neuroinflammation, cerebral perfusion using arterial spin labeling MRI imaging techniques, and indices of brain structure including volumetric and white matter analysis.

The New York Stem Cell Foundation (NYSCF) Research Institute is performing this research to accelerate diverse disease research using cells from the body (such as skin or blood cells) to make stem cells and other types of cells, conduct research on the samples, perform genetic testing, and store the samples for future use. Through this research, researchers hope to identify future treatments or even cures for the major diseases of our time.

Insomnia is a highly common, chronic disorder that is distressful for the patient but also for caregivers and can give rise to a heavy burden on the healthcare team. Sleeping aids like benzodiazepines and other sedatives (e.g., zolpidem, zopiclone) have been widely used to help treat insomnia. However, sleeping aids are also known to cause adverse drug reactions such as drowsiness and dizziness, that increases the risk of falls, driving impairment, visual impairment, cognitive impairment, and upon discontinuation may cause paradoxical rebound insomnia, delirium, and nightmares all of which exacerbate the initial insomnia. All of the negative aspects of sleeping aid use are exaggerated for older, frail adults. Some patients experience an early (young-age) onset dementia with a substantial component of insomnia. Due to the many risks associated with traditional sleeping aids they are often inappropriate in adults living with cognitive impairment and/or frailty. Lemborexant comes from a new class of medications for insomnia. Lemborexant is a dual orexin receptor antagonist that blocks the binding of wake-promoting neuropeptides orexin A and orexin B to their receptors orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R), which is thought to suppress wake drive. Unlike other traditional sleeping aids, lemborexant has not shown to be significantly associated with driving impairment, rebound insomnia, or dependence/withdrawal symptoms. Also, in clinical trials it only rarely causes the types of adverse events associated with benzodiazepines and other traditional sedatives and is less often associated with discontinuations due to adverse events. While lemborexant is available on the Canadian market it is unclear how this medication will be tolerated by patients living with an early onset dementia. Understanding the effectiveness and tolerability of lemborexant will be helpful in an N of 1 trial to understand the details of effect and effectiveness in individual patients.

The goal of this observational study is to compare the aggregation pattern of proteinopathies (alpha-synuclein, amyloid-beta, phosphorylated tau and transactive response DNA -binding protein 43 \[TDP43\]) in skin biopsies of patients with a neurodegenerative disease like Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis or normal pressure hydrocephalus. The main question it aims to answer is: * Is there a specific pattern of aggregation of proteinopathies in skin biopsies in each neurodegenerative disease in comparison to healthy control subjects? Skin biopsies will be analyzed using immunohistochemistry and immunofluorescence for detection of alpha-synuclein, amyloid-beta, phosphorylated tau and TAR DNA binding protein 43, and the aggregation patterns will be compared between patients with a neurodegenerative disease vs patient with normal pressure hydrocephalus vs healthy control subjects.

The Boston Cognitive Assessment (BoCA) is a self-administered online test intended for longitudinal cognitive monitoring. BoCA uses random not-repeating tasks to minimize learning effects. BoCA was developed to evaluate the effects of treatment in longitudinal clinical trials and available gratis to individuals and professionals.

Cognitive neurodegenerative diseases are a major public health issue. At present, the diagnosis of certainty is still based on anatomopathological analyses. Even if the diagnostic tools available to clinicians have made it possible to improve probabilistic diagnosis during the patient's lifetime, there are still too many diagnostic errors and sub-diagnostic in this field. The arrival of biomarkers has made it possible to reduce these diagnostic errors, which were of the order of 25 to 30%. This high error rate is due to different parameters. These diseases are numerous and often present common symptoms due to the fact that common brain structures are affected. These diseases evolve progressively over several years and their early diagnosis, when the symptoms are discrete, makes them even more difficult to diagnose at this stage. In addition, co-morbidities are common in the elderly, further complicating the diagnosis of these diseases. At present, the only cerebrospinal fluid (CSF) biomarkers that are routinely used for the biological diagnosis of neurodegenerative cognitive pathologies are those specific to Alzheimer's disease: Aβ42, Aβ40, Tau-total and Phospho-Tau. These biomarkers represent an almost indispensable tool in the diagnosis of dementia. It is therefore important to determine whether Alzheimer's biomarkers can be disrupted in other neurodegenerative cognitive pathologies, but also to find biomarkers specific to these different pathologies by facilitating the implementation of clinical studies which will thus make it possible to improve their diagnosis.