Investigating Complex Neurodegenerative Disorders Related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

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.

• 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 syndrome, Huntington disease or other related adult-onset 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.