Longitudinal neuropsychological and genetic linkage analysis of persons at risk for Huntington's disease

B. Giordani, S. Berent, M. J. Boivin, J. B. Penney, S. Lehtinen, D. S. Markel, Z. Hollingsworth, G. Butterbaugh, R. D. Hichwa, J. F. Gusella and al. et
Department of Psychiatry, University of Michigan, Ann Arbor.

OBJECTIVE: To determine (1) whether the neuropsychological profiles of healthy individuals at risk (AR) for Huntington's disease who were positive (AR/+) or negative (AR/-) for the Huntington's disease genetic marker differed from those of symptomatic patients with Huntington's disease and normal control individuals and (2) whether the neuropsychological performance of the two AR groups differed from each other on three assessments during a 4-year span. DESIGN: Case-control, double-blind study, with AR status determined by genetic linkage analysis (G8 probe), in addition to examination of trinucleotide repeats for most AR subjects. SETTING: The Neuropsychology Program in the Department of Psychiatry and the Department of Neurology at the University of Michigan Medical Center, Ann Arbor, a tertiary care center. PARTICIPANTS: Eight subjects matched as closely as possible for age, gender, and education in each of the following groups: AR/+, AR/-, normal control, and Huntington's disease. MEASURES: A battery of neuropsychological tasks, including measures of intelligence, memory, problem solving, and motor ability. RESULTS: Although both AR groups demonstrated variability on select intellectual subtests relative to normal subjects, they did not differ from each other on the three assessments during a 4-year span. Patients with Huntington's disease performed more poorly than the other groups across a range of neuropsychological measures. CONCLUSIONS: These results do not support previous evaluations concluding that AR/+ individuals demonstrate cognitive impairments as compared with AR/- individuals. Findings in earlier studies without genetic linkage analysis of lower performance of AR individuals, including children, as compared with normal controls may relate to extraneous environmental and familial issues that interfere with intellectual development.