179 Clinical Trials for Various Conditions
This pilot study will evaluate the effect of direct current (DC) electrical polarization of the brain on language, memory, reaction time, and mood in six patients with frontotemporal dementia (Pick's disease). There is no effective treatment available for cognitive impairment in patients with this condition. DC polarization sends a very weak current between two sponge pads placed on the head. In a previous study in healthy volunteers, DC polarization of the left prefrontal area of the brain increased verbal fluency, memory and attention, and motor reaction time in the study subjects. Patients between 35 and 75 years of age with frontotemporal dementia who have been referred to NINDS's Cognitive Neuroscience Section for an existing protocol will be offered participation in this study. Candidates will be screened with a neurological examination to confirm the diagnosis of frontotemporal dementia. Participants receive 40 minutes of DC polarization or sham polarization in each of two separate sessions. (No current is applied in the sham treatment). During the polarization, the patient rests quietly. Sponge pads that have been soaked in water are put on the left side of the head and above the right eye, and are held in place with elastic netting. Before the polarization and after about 20 minutes of polarization, patients undergo the following tests: * Language: Patients must say as many words beginning with certain letters as they can in 90 seconds. * Memory: Patients must remember a letter on a computer screen, and when the letter appears again, press the same letter on the keyboard. * Reaction time: Patients place pegs on a pegboard. * Mood: Patients place a mark on a line ranking how they feel.
Primary progressive aphasia (PPA) is a disorder characterized by gradual decline in speech-language ability caused by underlying neurodegenerative disease. PPA is a devastating condition that can affect adults as young as their 50's, depriving them of the ability to communicate and function in society. Along with Alzheimer's Disease and other Alzheimer's Disease Related Dementias (AD/ADRD), PPA is now identified earlier and with greater precision. Increasingly, patients and families seek options for behavioral and neuromodulatory treatments to address PPA's devastating effects on communication, prolong speech-language skills, and maximize quality of life. Studies have documented the robust benefits of speech-language telerehabilitation methods for persons with PPA, with in-home treatment resulting in immediate and long-term benefits. This investigation aims to further enhance the potency of these treatment approaches by pairing them with tailored neuromodulatory intervention that targets critical brain networks supporting treatment in each clinical subtype of PPA. The study will evaluate the feasibility and preliminary benefit of home-based transcranial direct current stimulation (tDCS) combined with evidence-based speech-language telerehabilitation methods. tDCS will be delivered to patients in their own homes and site of stimulation will be tailored for each clinical subtype of PPA. This project has the potential to enhance clinical management and rehabilitation for individuals with PPA by establishing the benefit of behavioral and neuromodulatory treatment that is neurobiologically-motivated and accessible for patients and families.
Background: Niemann-Pick type C (NPC) disease is a rare, progressive neurodegenerative disease that affects mainly the brain, liver, and spleen but also other parts of the body. There is no cure for NPC, and symptoms only get worse over time. Symptoms can include seizures, difficulty moving or talking, or dementia. But symptoms can vary among different people with the disease. Some may have seizures, while others do not, for example. Some people begin showing symptoms in childhood; in others, symptoms may not appear until they are adults. Researchers want to learn more about why NPC affects people differently. This natural history study will gather data from people with NPC in order to understand more about the disease and how it affects the body. Objective: This study will create the first and largest database about NPC. Eligibility: People of any age who have NPC. Design: Participants will have blood drawn from a vein. This will happen only once. The blood will be used to analyze the participants DNA. The participants medical records will be reviewed. The study team will collect data on participants NPC diagnosis and symptoms; they will record how long participants have had each symptom. The study team will also collect data on each participants age, sex, race, height, weight, medications, and other test results. The study team will communicate with participants. They will discuss the study and answer any questions. Participants will receive up to $190.
A pivotal, randomized, double-blind, placebo controlled, multi-center therapeutic study for patients age 4 and older with a confirmed diagnosis of Niemann Pick disease type C (NPC). The objective of this study is to evaluate the safety, tolerability and efficacy of N-acetyl-L-leucine (IB1001) compared to standard of care.
A prospective, randomized, double-blind, placebo controlled, multi-center therapeutic study for patients age 3 and older with confirmed diagnosis of Niemann Pick disease type C1 (NPC1). The objective of this study is to evaluate the safety, tolerability and efficacy of 2000 mg/kg dose of Trappsol Cyclo (hydroxypropyl betacyclodextrin) administered intravenously compared to standard of care. An open-label sub-study in countries following European Medicines Agency (EMA) guidance will enroll asymptomatic or symptomatic patients from infancy up to age 3 to evaluate safety in that population.
The purpose of this study is to provide continued access to treatment for NPC-1 after participation and completion of the Phase I trial CTD-TCNPC-101, when administered at doses of 1500 mg/kg and 2500 mg/kg by slow IV infusion over a period of 8 to 9 hours every two weeks.
Background: For people who have Niemann-Pick disease, type C1 (NPC1), cholesterol and other fats have trouble moving out of liver and other tissue cells. This makes the cells sick. Researchers want to find out if a drug called VTS-270 can help. Objective: To test if VTS-270 is safe and effective in treating chronic liver disease associated with NPC1. Eligibility: People ages 3-60 with NPC1 Design: Participants may be screened by phone or under another protocol. Participants will have visits once a month for 12 months. If they have intrathecal injections, the study may last 15 months or more. The first visit will last about 5 days. Others will last 2-3 days. Participants will get VTS-270 injected into a vein at each visit. They can also choose to have intrathecal injections. These are like spinal taps. Some visits will also include: Physical exam Urine tests Blood tests. A small tube or needle will be inserted into the participants vein to collect blood. The small tube will also be used to give the VTS-270. Hearing tests: For one test, participants will have electrodes taped to their head. These will record brain waves. Breathing tests Ultrasound of abdomen: Sounds waves will take pictures of the participant s body. Chest x-ray: This is a picture of the lungs.
This is a multinational, multicenter, open-label, rater-blinded prospective Phase II study which will assess the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the treatment of Niemann-Pick type C disease (NPC). There are two phases to this study: the Parent Study, and the Extension Phase. The Parent Study evaluates the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the symptomatic treatment of NPC. The Extension Phase evaluates the long-term safety and efficacy of IB1001 for the neuroprotective, disease-modifying treatment of NPC.
Niemann-Pick disease, type C (NPC) is a lethal, autosomal recessive, lysosomal storage disorder characterized by neurodegeneration in early childhood and death in adolescence. NPC results from mutation of either the Niemann-Pick C1 disease (NPC1) (\~95% of cases) or NPC2 genes. NPC is characterized by the endolysosomal storage of unesterified cholesterol and lipids in both the central nervous system and peripheral tissues such as the liver. Individuals with NPC demonstrate progressive central nervous system decline including inability to coordinate balance, gait, extremity and eye movements. Acute liver disease in the newborn/infant period is frequently observed, but subsequently resolves. However, chronic, sub-clinical liver disease persists. Intrathecal 2-Hydroxypropyl-β-Cyclodextrin (HP-β-CD, VTS-270), also known as adrabetadex, has proven effective in reducing the signs and prolonging life in animal models and Phase 1/2a data support efficacy in NPC1 patients. Adrabetadex (VTS-270) also has been shown to be effective in treating liver disease in the NPC1 cat. This Phase 1/2a, open-label, multiple ascending dose trial will evaluate whether adrabetadex (VTS-270) administered intravenously is effective in treating acute liver disease in NPC1 infants.
The purpose of this research study is to evaluate tau distribution in the brain of subjects with: FTD caused by different genetic mutations, any mutation carriers (with or without symptoms), any non-mutation carrier, any sporadic FTD, normal controls.
A prospective, randomized, double-blind, placebo controlled therapeutic study in participants with confirmed diagnosis of Niemann-Pick disease type C (NPC). The purpose of this study is to assess the efficacy and safety of arimoclomol (compared to placebo) when it is administered as an add-on therapy to the participant's current prescribed best routine clinical care; participant's routine clinical care may, or may not, include miglustat. The CT-ORZY-NPC-002 study has been expanded to include an open label paediatric sub-study including participants aged 6 to \<24 months at study enrolment.
The purpose of this study is to provide subjects who have completed participation in a Phase 2 or Phase 3 trial of LMTM continued access to therapy and to evaluate the long-term safety of LMTM.
Niemann-Pick disease type C (NPC) is a lethal, autosomal recessive, lysosomal storage disorder characterized by neurodegeneration in early childhood and death in adolescence. The causative genes NPC1 (about 95% of cases) and NPC2 (about 5% of cases) are involved in the intracellular trafficking of lipids and cholesterol. Mutations on either of these genes lead to progressive accumulation of unesterified cholesterol and other lipids in the central nervous system (CNS). Vorinostat is a histone deacetylase inhibitor that has been shown in vivo to increase mutant NPC1 protein levels and to reverse cellular accumulation of unesterified cholesterol. Vorinostat has been labeled by the FDA for treatment of cutaneous T-cell lymphoma. In this Phase I, non-randomized, open-label, single-center study, we plan to study whether Vorinostat can be repurposed to treat patients with NPC1. Our primary objective is to determine the safety and tolerability of Vorinostat in NPC1 disease. Our secondary objectives will be to determine biochemical efficacy of Vorinostat to increase expression of NPC1 protein and normalize lipid and protein biomarkers. This study will enroll up to 12 NPC1 patients and test the safety of two dose levels (200 and 400 mg). Drug will be administered on a 3 days on/4 days off schedule for 3 months at each dose level. Patients will be evaluated at the NIH Clinical Center at 0, 3 and 6 months. Safety will be assessed by adverse events (AEs), clinical laboratory tests and physical examinations. Biochemical efficacy will be assessed by measurement of serum and cerebral spinal fluid biomarkers. Clinical efficacy will be evaluated by audiologic testing, assessment ataxia, and swallowing studies.
Niemann-Pick Disease, Type C (NPC) is a rare neurodegenerative disorder with a wide clinical spectrum and variable age of onset. Classically, children with NPC demonstrate neurological dysfunction with cerebellar ataxia (an inability to coordinate balance, gait, extremity and eye movements), dysarthria (difficulty speaking), seizures, vertical gaze palsy (ability to move eyes in the same direction) motor impairment, dysphagia (trouble swallowing), psychotic episodes, and progressive dementia. There is no curative treatment for NPC and it is a lethal disorder. The purpose of this protocol is to obtain both baseline and rate of progression data on a clinical and biochemical markers that may later be used as outcome measures in a clinical trial. Specifically, this study will examine and characterize the longitudinal progression of neurocognitive symptoms of NPC with the goal of identifying early markers of disease progression that may be utilized in later trials to evaluate treatment efficacy.
This study is designed to document the loss of sociomoral emotions (like empathy, guilt, and embarrassment) in patients with behavioral variant frontotemporal dementia. The loss of these emotions, which function as the motivators for social behavior, will manifest in specific interpersonal behaviors. These behaviors will correlate with regional changes in regional changes in medial frontal and anterior temporal lobes. These social and emotional changes will be compared with a young-onset Alzheimer's disease comparison group.
Background: * Niemann-Pick disease type C (NPC) is a genetic disorder that results in progressive loss of nervous system function by affecting the membranes of nerve cells. There is no known cure for NPC. * N-acetyl cysteine (NAC) is a drug that has been approved by the Food and Drug Administration to use either orally or IV for the treatment of acetaminophen (Tylenol) poisoning or as an aerosol to reduce the stickiness of mucous in patients with cystic fibrosis. In the body, NAC is converted to an amino acid called cysteine, which cells can convert to a chemical called glutathione. Glutathione is important in helping cells deal with oxidative stress. Based on a number of experiments in cells, mice and patients with NPC, we believe that oxidative stress is increased in NPC. If we can increase glutathione levels, we may be able to decrease the oxidative stress. Objectives: - To test the safety and effectiveness of N-acetyl cysteine to treat Niemann-Pick disease (type C). Eligibility: - Individuals at least 1 year of age who have been diagnosed with NPC. Design: * Patients entering this study will be seen at the National Institutes of Health Clinical Center four times during the 20 weeks of the study. These admissions will occur at the start of the study and at weeks 8, 12, and 20. The first NIH visit will last 2 days, and the other visits will last 1 day. * Patients will participate in a two-stage study: a period of 8 weeks receiving NAC and a second period of 8 weeks when receiving a placebo (a pill without NAC). Every patient participating in this study will receive NAC during one of the two time periods. * The two treatment periods will be separated by a wash-out period, 4 weeks when patients will receive neither NAC nor placebo. Patients will also have a 4-week wash-out period at the beginning of the study. Most physician-prescribed medications, such as seizure medications, will be allowed. * During each visit, examinations, procedures, and tests will be done, including blood and urine samples.
The purpose of this study is to determine the safe range of single doses of rhASM administered to adults with ASM deficiency.
This study will evaluate clinical and laboratory tests that might be useful in determining if an investigational drug can slow the progression of Niemann-Pick Disease, Type C (NPC), a genetic disorder that results in progressive loss of nervous system function. The study will: 1) look for a clinical or biochemical marker that can be used as a measure of response to treatment, and 2) define the rate of progression of biochemical marker abnormalities in a group of NPC patients who will later be invited to enroll in a treatment trial. Patients of any age with NPC may be eligible for this study. Participants undergo the following procedures every 6 months during 4- to 5-day admissions at the NIH Clinical Center. * Medical evaluation, including medical history, physical exam, neurological exam, neuropsychometric evaluation, and blood and urine tests. * Lumbar puncture (spinal tap): A sample of cerebrospinal fluid (CSF), the fluid that bathes the brain and spinal cord, is obtained for study. After administration of a local anesthetic, a small needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle. * Eye exam and eye movement study: The pupils of the eye are dilated to examine the structures of the eyes. For the eye movement study a special contact lens is placed on the eye and the patient looks at a series of target light spots moving on a screen. * Hearing tests. * Electroretinography (in patients who can cooperate with the test) to measure the function of the retina. Before the test, the patient's pupils are dilated and an electrode (small silver disk) is taped to the forehead. The patient sits in a dark room for 30 minutes and then a special contact lens is placed on one eye after it has been numbed with drops. The contact lens senses small electrical signals generated by the retina when lights flash. During the ERG recording, the eye is stimulated with flashes of light projected inside a hollow sphere. After the test, a full eye exam is done and photographs of the retina are taken. * Magnetic resonance imaging (MRI): This test uses a magnetic field and radio waves to produce images of the brain and obtain information about brain chemicals. The patient lies on a table that can slide in and out of the scanner (a narrow cylinder), wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. Patients who cannot remain still in the scanner may be sedated for the test. * Psychometric testing: Patients complete questionnaires. * Photographs of the patient may be taken for use in teaching sessions or scientific presentations or publications, with the patient's consent. Patients may be recognizable, but are not identified by name. * Pregnancy test in all female patients over 10 years of age at the beginning of each admission to the Clinical Center.
Primary progressive aphasia (PPA) is a progressive neurological disorder that causes a gradual decline in communication ability as a result of selective neurodegeneration of speech and language networks in the brain. PPA is a devastating condition affecting adults as young as in their 50's, depriving them of the ability to communicate and function in society. As a result of improved diagnostic precision, PPA is now identified with greater accuracy and frequency and, increasingly, patients and their families seek options for behavioral treatments to ameliorate the devastating effects on their communication, prolong speech language skills, and maximize quality of life. Speech-language treatment outcomes from our group and others are encouraging, confirming that behavioral intervention may lead to improvements in trained behaviors and, for some interventions, lasting and generalized benefit. Most speech-language interventions for individuals with PPA that have been explored in the literature are restitutive, or impairment-based in nature, and have not addressed the full range of severity and phenotypic variability in this population. The investigators will evaluate the utility of a novel, multicomponent intervention that incorporates elements of restitutive (e.g., word finding strategic training, script training), compensatory (e.g., multimodal communication, communication book), and care partner-focused treatment to meet the needs of individuals varying in clinical presentation and severity.
The primary objective of this research is to evaluate the effects of non-invasive brain stimulation and computerized cognitive training on executive functioning in individuals with Primary Progressive Aphasia (PPA), mild cognitive impairment (MCI), or dementia. In this study, investigators will use transcranial direct current stimulation (tDCS) to stimulate the left dorsolateral prefrontal cortex (DLPFC). Previous studies have demonstrated that tDCS over the DLPFC led to improvements in attention deficit caused by stroke, Parkinson's Disease, and major depression as well as language deficits caused by neurodegenerative conditions such as primary progressive aphasia or mild cognitive impairment. The investigators seek to expand on this literature by investigating how anodal tDCS paired with and without cognitive training will impact executive functioning in PPA with Frontotemporal Dementia or Alzheimer's Disease pathology and Mild Cognitive Impairment/Alzheimer's Disease (e.g. shifting, updating, monitoring, and manipulation).
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.
This study will evaluate evidence-based treatments for adults with mild Primary Progressive Aphasia (PPA). The aim of the study is to help identify efficacious communication and quality of life interventions for those with PPA and their care-partners. Participants with a diagnosis of PPA and their actively-engaged care partners will be involved in the study for 12 months. Each participant will receive a iPad equipped with the necessary applications and features for the study. Participants will complete evaluations, speech therapy sessions with a speech and language therapist, and sessions with a licensed social worker or related clinician. They will have access to Communication Bridge, a personalized web application to practice home exercises that reinforce treatment strategies. There are no costs to participate in this study.
The purpose of the study is to test whether low level electric stimulation, called transcranial Direct Current Stimulation (tDCS), on the part of the brain (i.e., pre-supplementary motor area and left inferior frontal gyrus) thought to aid in memory will improve speech and language difficulties in patients with primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). The primary outcome measures are neuropsychological assessments of speech and language functions, and the secondary measures are neuropsychological assessments of other cognitive abilities and electroencephalography (EEG) measures.
Primary progressive aphasia (PPA) is a progressive neurological disorder that causes a gradual decline in communication ability as a result of selective neurodegeneration of speech and language networks in the brain. PPA is a devastating condition affecting adults as young as their 40's or 50's, depriving them of the ability to communicate and function in society. There has been significant progress in discovering the neurobiological mechanisms that underlie PPA and in identifying its clinical phenotypes. With these advances, we are poised to investigate behavioral treatments that are grounded in modern cognitive and neuroanatomical concepts. Research documenting the efficacy of speech-language treatment for PPA is emerging, but limited. Systematic research is needed to establish best clinical practices in this unique patient population for whom pharmacological treatment remains elusive. The long-term objectives of this project are to provide evidence-based treatment methods addressing the speech and language deficits in PPA and to determine the neural predictors of responsiveness to intervention. The study has three main goals that build on the findings of our previous work: 1) to examine the utility of treatments designed to facilitate significant, generalized and lasting improvement of speech-language function in PPA, 2) to determine whether treatment alters the trajectory of decline in PPA by comparing performance on primary outcome measures in treated versus untreated participants after a one-year interval, and 3) to identify imaging predictors (gray matter, white matter, and functional connectivity measures) of responsiveness to behavioral intervention in individuals with PPA. In order to accomplish these aims, we will enroll 60 individuals with PPA, who will undergo a comprehensive multidisciplinary evaluation and neuroimaging. Subsequently, participants will be enrolled in treatment designed to promote lasting and generalized improvement of communicative function in core speech-language domains. Participants will be followed for up to one-year post-treatment in order to determine long-term effects of rehabilitation, and their performance will be compared with a historical cohort of untreated PPA patients. This ambitious study and the necessary recruitment will be possible due to an ongoing collaboration with the UCSF Memory and Aging Center, a leading institution in the field of PPA research. The study will broaden the evidence base supporting the efficacy of speech-language intervention in PPA and will provide novel evidence regarding neural predictors of treatment outcomes, with the potential to inform clinical decision-making and improve clinical care for individuals with this debilitating disorder.
The purpose of this research is to better understand how dementia affects activity in different parts of the brain.
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.
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.
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.
The goal of this study is to remediate word-finding problems in patients who have Primary Progressive Aphasia (PPA) or Alzheimer's Disease and to delay the further progression of word-finding impairment. The current approach is novel in that it contains a prophylaxis component in which the investigators attempt to strengthen neural connections that remain functional, making them more resistant to degradation as the disease progresses. While the study is specific in its targeting of word-finding problems, a successful outcome would bode well for other studies aimed at prevention or reversal of declining cognitive functions in dementia. One set of participants with PPA will receive practice with picture naming in two conditions: viewing the picture and repeating the name; and viewing the picture with its written name, plus reading and writing the name. Another set of participants with PPA or Alzheimer's Disease will be trained in two different conditions: learning about the word's semantic features (meaning); and learning about the word's lexical features (letters and sounds). Naming of pictures trained in each of these conditions will be compared, at three time intervals post-training, with naming of pictures tested before the study but never trained. It is predicted that the pairing of the picture with its written name, combined with the motor task of writing the name, will result in a greater ability to name the picture at a later date than simple practice viewing the picture and repeating the name. Furthermore, it is predicted that participants who have difficulty understanding concepts will be more likely to respond to semantic treatment, while participants who have difficulty connecting words with concepts will be more likely to respond to lexical treatment.