New Sensitive Measures of Executive Functioning in Premotor Huntington's Disease (S20.002)

OBJECTIVE: To investigate the sensitivity of the NIH EXAMINER executive function composite scores to cognitive changes in premotor Huntington9s disease (pmHD) and to caudate volume using 3T structural MRI. BACKGROUND: Huntington disease is an inherited neurodegenerative disease characterized by progressive motor, cognitive, and psychiatric symptoms. Although clinical diagnosis typically is dependent on the presence of motor abnormalities, cognitive changes and caudate volume loss are often observed prior to motor diagnosis. Sensitive neuropsychological assessments are needed to identify patients in early stages of the disease and as outcome measures for neuroprotective treatment trials. Identifying problems with executive functions is particularly compelling given their association with functional decline (e.g., early unemployment). The NIH EXAMINER (Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research) is a new neuropsychological battery assessing executive function and designed with clinical trials in mind. It has alternate forms and produces composite scores using item response theory with excellent psychometric properties. DESIGN/METHODS: Fifteen patients with pdHD and 14 matched healthy controls were compared using independent samples t-tests on the NIH EXAMINER9s Total Executive Composite, as well as on composites that represent subcomponents of executive functions: the Working Memory, Fluency, and Cognitive Control Composites. The Composites were correlated with 3T caudate volumes in pmHD. RESULTS: The pmHD patients scored lower on the Executive Composite and on the Working Memory Composite, both ps CONCLUSIONS: The NIH EXAMINER Executive and Working Memory Composites are sensitive markers of cognitive changes and caudate volume size (presumed atrophy) in pmHD. Results support the idea that executive dysfunction, and particularly working memory deficits, might precede motor symptoms and are viable early disease markers. Disclosure: Dr. You has nothing to disclose. Dr. Satris has nothing to disclose. Dr. Apple has nothing to disclose. Dr. Frazier has nothing to disclose. Dr. Sha has nothing to disclose. Dr. Hess has received personal compensation in an editorial capacity for the American Journal of Neuroradiology and the Public Library of Science. Dr. Geschwind has received personal compensation for activities with Gerson Lehrman Group, Clinical Advisors and MedaCorp, and Eisai, Inc. Dr. Kramer has nothing to disclose. Dr. Possin has nothing to disclose.