investigating complex neurodegenerative disorders related to amyotrophic lateral sclerosis and frontotemporal dementia

Conditions: Frontotemporal Dementia; Amyotrophic Lateral Sclerosis; Progressive Supranuclear Palsy

Summary: 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.

objectives the primary objective is to evaluate patients referred with a diagnosis of frontotemporal dementia (ftd), amyotrophic lateral sclerosis (als), or related adult-onset neurodegenerative disorders to assess patient eligibility for ongoing protocols. the secondary objective is to develop and maintain a registry of characterized patients and presymptopmatic carriers of gene mutations that cause als-ftd spectrum disorders. the exploratory objectives are to obtain biospecimens from clinically characterized patients to carry out laboratory-based studies aimed at understanding the molecular pathways and genetic overlap between these neurodegenerative disorders and to perform 7 tesla magnetic resonance imaging studies to identify imaging biomarkers of neurodegeneration. study population adults referred with clinical diagnoses of frontotemporal dementia, motor neuron disorder, or related adult-onset neurodegenerative disorder. presymptomatic carriers of genes known to cause familial ftd or als design all participants will undergo clinical tests to confirm diagnoses and to stage disease severity, including a standard battery of tests to measure cognitive and motor functions. participants may opt-in for research procedures such as phlebotomy, skin biopsy, leukapheresis, and lumbar puncture to obtain biospecimens for laboratory research, and magnetic resonance imaging or transcranial magnetic stimulation may be used to explore biomarkers of disease. outcome measures clinical information will be analyzed as part of our research to identify common features and differences among participants.

Eligibility criteria:
* inclusion criteria: patients will be included if they * are age 18 or older * have been given a diagnosis by a neurologist of frontotemporal dementia, primary progressive aphasia, semantic dementia, motor neuron disorder, amyotrophic lateral sclerosis, progressive bulbar palsy, corticobasal neurodegenerative disorder or * carry a mutation in a gene that causes familial als or ftd exclusion criteria: patients will be excluded if they * have other major neurological or medical diseases that may cause progressive weakness or cognitive dysfunction, such as structural brain or spinal cord disease, metabolic diseases, paraneoplastic syndromes, infectious diseases, peripheral neuropathy or radiculopathy or other significant neurological abnormalities. * have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe * require daytime ventilator support at the time of study entry * are unable to travel to nih * patients with pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, or shrapnel fragments, metal fragments in the eye) will not be excluded but will not undergo magnetic resonance imaging. * patients with tattoos above the neck or permanent make up will be excluded from undergoing 7t mri.

Keywords: tdp-43 progressive supranuclear palsy motor neuron disease frontotemporal dementia corticobasal syndrome natural history