Complex Neurodegenerative Disorders Clinic

National Institute Of Neurological Disorders And Stroke

Investigators

Abstract

Although neurodegenerative disorders were historically considered as discrete diseases, this concept has been challenged by scientific discoveries showing overlapping clinical symptoms, genes, and pathology. Neurodegenerative disorders associated with the intracellular aggregation of misfolded TDP-43 or microtubule-associated tau proteins may present with a mixture of cognitive, language, and motor symptoms. Patients may be diagnosed with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), or primary progressive aphasia (PPA). Some causative genes have been found for each disorder, although most patients have sporadic disease. Interestingly, the same genetic mutation can produce different clinical phenotypes. The link between the gene mutations and pathology in these disorders may lie in the molecular and cellular processes affected by mutant gene products. As the field of neurology moves more towards the molecular characterization of neurodegenerative disorders, there is a need to understand clinical phenomenology in the context of pathology and genetic or epigenetic defects that are the drivers of disease. Given the broad spectrum of neurological symptoms in this family of disorders, this clinic brings together an outstanding and energetic group of physicians and researchers with a wide range of clinical expertise and scientific approaches. Patients undergo clinical and cognitive assessments, imaging, and collection of biospecimens for research studies. The objective is to gain knowledge that will set the stage for precision medicine in which therapy is tailored to the underlying cause of each patient's disease. The Complex Neurodegenerative Disorders Clinic continues to operate smoothly in FY 2025. The clinic staff organizes clinical studies that help to establish the diagnosis, as well as a standard battery of clinical and cognitive testing. Biospecimens from participants are collected for research purposes and shared with collaborators. Each month, the clinic holds a multidisciplinary conference with neurologists, neuropsychologists, and health personnel involved in the clinic to discuss individual patients and their diagnosis and suitability for research protocols. Patients who are found to be eligible for ongoing research studies are referred to those studies. Select participants have undergone 7-tesla imaging in collaboration with Laboratory of Functional & Molecular Imaging. Biosamples continue to be collected for collaboration with the Section of the Infections of the Nervous System. Participants may sign up for a registry for receiving information on future NIH studies and an annual questionnaire to update their current status and continued interest in research. Several participants are also referred to other ongoing NIH protocols.