Research: Longitudinal Study of Cognitive Impairment in ALS Principal Investigators: Paul H Gordon, MD Hiroshi Mitsumoto, MD Karen Marder, MD Judith G. Rabkin, PhD Martin McElhiney, PhD Yaakov Stern, PhD A new longitudinal study, collecting data on cognitive dysfunction from a large clinic population of patients with ALS will begin at the Center in December 2006. The specific aims are to determine whether changes in cognition correlate with motor decline and vice versa; to determine pathological correlates of clinical cognitive dysfunction; to pilot eye movement assessments of cognitive changes in patients with advanced ALS; to design a clinical trial for a subgroup of patients with cognitive impairment; and to reach a definition of dementia and cognitive impairment in ALS. BACKGROUND: Changes in mental abilities or cognition are increasingly recognized in ALS, but the type, occurrence, and best treatment options are unknown. Frontotemporal dementia (FTD) produces early changes in behavior, function and language. These changes have both preceded and followed the diagnosis of ALS. Cases of ALS and FTD existing together usually show inclusions, or abnormal structures, in the motor neurons as well as in the frontal and temporal lobes of the brain. However, the prevalence of FTD occurring along with ALS has not been determined. GOALS: To develop a cognitive screen or series of questions that can be used to help identify patients prone to cognitive deficits. To better understand the co-occurrence of ALS and dementia. To conduct a large longitudinal study to define the range and clinical implications of cognitive impairment in ALS. STUDY DESIGN: The questionnaire, given at three month intervals, will include verbal fluency tests, word association and generation exercises as well as memory, visual and spatial tests, and tools to measure focus, planning and organization ability. These tests will be given at ALS clinics and used to determine the presence of dementia in ALS patients. In addition, questionnaires that will appraise the behavioral symptoms of the patient will be given to the caregiver. IMPORTANCE: This study will help identify patients prone to cognitive deficits and improve our understanding of how to treat these impairments in ALS. Better understanding of the overlap of FTD and ALS may provide important clues to the cause of the diseases. Clinical research is entirely dependent upon the participation of patients with ALS. By participating, patients take a difficult situation and make a meaningful contribution to our common goal. Our research and future patients with ALS will benefit from your dedicated participation. Research Update: DNA Banking Under the direction of Hiroshi Mitsumoto, MD, over 60 centers through out the United States and Canada have been collecting DNA samples from patients with motor neuron disease (and healthy controls) and storing them in a central repository. From January 2006 to November 2006 the catalog went from 27 samples to 1820 samples, and more are being collected. The repository will facilitate researchers hoping to identify mutated genes and a predisposition to MND/ALS.