Variability in cognitive function among persons at high genetic risk of Huntington's disease.

The present study explores cognitive variability and specificity of cognitive decline in persons at high genetic risk (AR+ persons) of Huntington's disease (HD). Risk status was determined by RFLP markers. Three subgroups were defined according to neuropsychological test performance. One subgroup showed a typical HD pattern of impairment, a second group selectively impaired verbal memory function, and a third group was more heterogeneous. Verbal memory function was frequently impaired among AR+ persons. The specificity of verbal memory dysfunction was evaluated by using a multivariate statistical clustering procedure. While 60% of the AR+ persons were allocated to clusters typical of "subcortical dementia", most AR- persons were allocated to a "normal" cluster. However, the variability was wide within both the AR+ and AR- group. The heterogeneity among AR+ persons was consistent with findings in genetic, neuroimaging, and neuropathological studies of HD. Multidisciplinary studies should be performed to better understand biological determinants of cognitive variability, and to facilitate clinical diagnosis and councelling in individual AR+ persons.