17 Clinical Trials for Various Conditions
The purpose of this study is to establish the feasibility of a program of remotely supervised transcranial direct current stimulation (RS-tDCS) paired with language skills practice for people living with the semantic or logopenic variants of primary progressive aphasia (PPA). There are currently no established standard-of-care treatments for PPA. This study will evaluate whether RS-tDCS combined with language skills practice is a feasible study design for individuals with PPA.
This is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and semantic variants of primary progressive aphasia (naPPA and svPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham transcranial direct current stimulation (tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and up-to 24 weeks following completion of treatment. The investigators will examine changes in language performance induced by tDCS + mCILT compared to sham tDCS + mCILT. The investigators will also use network science to analyze brain imaging (fMRI) data to identify network properties associated with baseline PPA severity and tDCS-induced changes in performance. This study will combine knowledge gained from our behavioral, imaging, and network data in order to determine the relative degrees to which these properties predict whether persons with PPA will respond to intervention.
This is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and logopenic variants of primary progressive aphasia (naPPA and lvPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham high-definition transcranial direct current stimulation (HD-tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and 3 months following completion of treatment. The 3-month follow-up will be the primary endpoint. The investigators will examine changes in language performance induced by HD-tDCS + mCILT compared to sham HD-tDCS + mCILT. The investigators will also use network science to analyze brain imaging (fMRI) data to identify network properties associated with baseline PPA severity and tDCS-induced changes in performance. This study will combine knowledge gained from our behavioral, imaging, and network data in order to determine the relative degrees to which these properties predict whether persons with PPA will respond to intervention.
The aim of this study is to create a repository of both cross-sectional and longitudinal data, including cognitive, linguistic, imaging and biofluid biological specimens, for neurodegenerative disease research and treatment.
Primary progressive aphasia (PPA) is a neurodegenerative disease that affects first and foremost language abilities. There are three different variants of PPA, each a relatively distinct speech and language profile. For individuals with non-fluent variant PPA (nfvPPA), a core symptom is apraxia of speech (AOS), which is defined as an oral motor speech disorder. Such a disorder inhibits one's ability to translate speech plans into motor plans and results in longer segmental durations and reduced rate of syllabic production. This research project investigates the behavioral and neuromodulatory effects of transcranial direct current stimulation (tDCS) during language therapy in participants with nfvPPA over time. Anodal tDCS targeting the left inferior frontal gyrus (IFG) administered in combination with language therapy is expected to be more beneficial when compared to language therapy alone (sham). The investigators believe tDCS during language therapy will 1) improve language performance or decrease rate of decline, 2) promote better-sustained effects at 2 weeks and 2 months post-treatment, and 3) produce generalization to untrained language items and some other cognitive functions. Resting-state fMRI, diffusion tensor imaging (DTI), and volumetric data are also collected to investigate changes in functional brain connectivity associated with tDCS in individuals with PPA. A better understanding of the therapeutic and neuromodulatory mechanisms of tDCS as an adjunct to language therapy in nfvPPA may have a significant impact on the development of effective therapies for PPA, and may offer insight into ways of impeding neurodegeneration that may improve patients' quality of life, as well as extend patients' ability to work and manage patients' affairs.
Primary progressive aphasia (PPA) is a neurodegenerative disease that affects first and foremost language abilities. Mild cognitive impairment (MCI) is slowly progressive decline in a single domain of cognition (e.g. language) not attributable to motor or sensory loss, without impediment of social or occupational function. MCI can be an early sign of neurodegenerative disease, or can be due to normal aging. When language is the prominent affected domain in MCI, the person may later meet criteria for PPA or may progress to the clinical syndrome of Alzheimer's dementia. Spelling, naming, and working memory (e.g. repetition) are among the language abilities affected early in the course of PPA or language-centered MCI, and different variants have distinct deficits in these domains. This research project investigates the behavioral and neuromodulatory effects of high definition transcranial direct current stimulation (HD-tDCS) during language therapy in PPA participants over time. Anodal HD-tDCS targeting the left inferior frontal gyrus (IFG) administered in combination with language therapy is expected to be more beneficial when compared to language therapy alone. It will 1) improve language performance or decrease rate of decline, 2) have better-sustained effects at 2 weeks and 2 months post-treatment, and 3) produce generalization to untrained language items and some other cognitive functions. Resting-state fMRI, diffusion tensor imaging (DTI), and volumetric data are also collected to investigate changes in functional brain connectivity associated with HD-tDCS in individuals with PPA. A better understanding of the therapeutic and neuromodulatory mechanisms of HD-tDCS as an adjunct to language therapy in PPA may have a significant impact on the development of effective therapies for PPA and MCI, and may offer insight into ways of impeding neurodegeneration that may improve patients' quality of life, as well as extend their ability to work and manage their affairs.
The purpose of this research is to better understand how dementia affects activity in different parts of the brain.
The primary goal of this pilot project is to adapt an evidence-informed on-line psychoeducation program (Tele-Savvy) to address the unique challenges facing informal caregivers of those living with PPA and geared toward achieving caregiver mastery in this population.
AD afflicts over 5.5. million Americans and is one of the most expensive diseases worldwide. In AD the variant in which language functions are most affected are referred to as 'logopenic variant Primary Progressive Aphasia' (lvPPA). Language deficits dramatically impair communication and quality of life for both patients and caregivers. PPA usually has an early onset (50-65 years of age), detrimentally affecting work and family life. Studies have identified verbal short-term memory/working memory (vSTM/WM) as a primary deficit and cause of language impairment. In the first cycle of this award, the investigators asked the question of whether language therapy effects could be augmented by electrical stimulation. The investigators conducted the largest to-date randomized, double-blind, sham-controlled, crossover, clinical trial to determine the effects of transcranial direct current stimulation (tDCS) in PPA. The investigators found that tDCS over the left inferior frontal gyrus (L_IFG), one of the major language hubs in the brain, significantly enhanced the effects of a written naming and spelling intervention. In addition, findings demonstrated that tDCS modulates functional connectivity between the stimulated area and other networks (e.g. functionally and structurally connected areas), and that tDCS modulates the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In terms of tDCS, the investigators have been identified several predictors to determine the beneficience of tDCS including (a) PPA variant, (b) initial performance on cognitive/language tasks, particularly vSTM/WM, and (c) initial white-matter integrity and structure. These findings support the notion that tDCS benefits generalize beyond the treatment tasks and has led to the important question of the present study: How can we implement treatments to product benefits that maximally generalize to untrained but vital language/cognitive functions. To address the above question, the investigators will test recent neuroplasticity theories that claim that the benefits of neuromodulation to language-specific areas generalize to other language functions within the language network, while neuromodulation of a domain-general/multiple-demands area generalizes to both domain-general, executive and language functions. The two areas to be stimulated will be the supramarginal gyrus (SMG) and left dorsolateral prefrontal cortex (DLPFC) respectively. The left supramarginal gyrus (L_SMG) in particular, specializes in phonological processing, namely phonological verbal short-term memory (vSTM), i.e., the ability to temporarily store phonological (and graphemic) information in order. The domain of vSTM affects many language tasks (repetition, naming, syntax), which makes it an ideal treatment target and the L_SMG an ideal stimulation target, since generalization of tDCS effects to other language tasks is driven by the function (computation) of the stimulated area. By testing a fundamental principle of neuromodulation in a devastating neurodegenerative disorder, the investigators will significantly advance the field of neurorehabilitation in early-onset dementias. Aim 1: To determine whether vSTM/WM behavioral therapy combined with high definition (HD)-tDCS over the L_SMG will induce more generalization to language-specific tasks than to executive tasks, whereas stimulation over the LDPFC will induce equivalent generalization to both executive and language-specific tasks. Aim 2: To understand the mechanism of tDCS by measuring tDCS-induced changes in network functional connectivity (FC) and GABA in the LSMG and LDPFC. The investigators will carry out resting-state functional magnetic resonance imaging (rsfMRI), (MPRAGE), diffusion-weighted imaging (DWI), perfusion imaging (pCASL), and magnetic resonance spectroscopy (MRS), before, after, and 3-months post-intervention. Aim 3: To identify the neural, cognitive, physiological, clinical and demographic characteristics (biomarkers) that predict sham, tDCS, and tDCS vs. sham effects on vSTM and related language tasks in PPA. The investigators will evaluate neural (functional and structural connectivity, cortical volume, neuropeptides, and perfusion), cognitive (memory, attention, executive) and language functions, clinical (severity), physiological (sleep), and demographic (age, gender) characteristics, and the investigators will analyze the effects on vSTM and other language/cognitive outcomes immediately after intervention and at 3 months post-intervention.
This study aims to evaluate the effectiveness of a therapy called High-Definition Transcranial Direct Current Stimulation (HD-tDCS) for the treatment of the language deficits experienced by people with a type of Primary Progressive Aphasia. This study uses a combination of brain imaging, language assessment, language training sessions, and HD-tDCS therapy as well as placebo therapy sessions.
People with Primary Progressive Aphasia (PPA) are is a debilitating disorder characterized by the gradual loss of language functioning, even though cognitive functioning is relatively well preserved until the advanced stages of the disease. There are very few evidence-based treatment options available. This study investigates the behavioral and neural effects of multiple consecutive tDCS sessions paired with language therapy targeting verbs in sentences with individuals with PPA.
Primary progressive aphasia (PPA) includes three variants. Two such variants, the non-fluent/agrammatic variant (nfvPPA) and the logopenic variant (lvPPA), are characterized by progressive word-finding difficulties and effortful speech. Efforts to slow or halt this progression have been largely unsuccessful. As such, there is a desperate need for novel treatment strategies in PPA. Repetitive transcranial magnetic stimulation (rTMS) is a safe, non-invasive way of stimulating cortical targets in a focal and reproducible manner. Therapeutic benefits from rTMS have been demonstrated when it is applied in many sequential sessions. For example, repeated sessions of rTMS to left dorsolateral prefrontal cortex (dlPFC) is approved by the US Food and Drug administration as a treatment for major depressive disorder. With respect to language, high frequency rTMS increases the response rate for picture naming in healthy individuals. rTMS has also been shown to improve the number of correct naming responses in patients with Alzheimer's disease. Further, in a sham controlled study, Cotelli and colleagues demonstrated that in a group of 10 nfvPPA patients high frequency rTMS over the left and right dlPFC during object and action naming tasks improved the percent of correct responses for action, but not object naming. Finally, in a sham controlled single case study, Finocchiaro et al. applied high frequency rTMS to the left inferior mid-frontal gyrus for 3 sessions consisting of five consecutive days (treatment or sham). They found a significant and lasting improvement in the patient's performance on verb production when comparing active rTMS to sham rTMS or baseline. These studies have contributed valuable insights into the potential use of rTMS in treating the language symptoms of PPA patients.
This study is designed to learn more about overall tau burden in the brain of patients with Primary Progressive Aphasia (PPA) and Frontotemporal Dementia.
The study is designed to determine the relationship between structural and functional changes in the brain on imaging and progression of speech and language, neurological and neuropsychological features in patients with neurodegenerative apraxia of speech (AOS).
The study is designed to determine whether there are clinical features that can be used as biomarkers to predict whether underlying Alzheimer's pathology is the cause of a speech and language based dementia. The primary hypothesis is that the proportion of patients who test positive for beta-amyloid deposition will vary across different speech and language based dementias.
Frontotemporal Lobar Degeneration (FTLD) is the neuropathological term for a collection of rare neurodegenerative diseases that correspond to four main overlapping clinical syndromes: frontotemporal dementia (FTD), primary progressive aphasia (PPA), corticobasal degeneration syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). The goal of this study is to build a FTLD clinical research consortium to support the development of FTLD therapies for new clinical trials. The consortium, referred to as Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL), will be headquartered at UCSF and will partner with six patient advocacy groups to manage the consortium. Participants will be evaluated at 14 clinical sites throughout North America and a genetics core will genotype all individuals for FTLD associated genes.
The investigators aim to learn more about symptoms suggestive of a neurodegenerative process.