EVIDENCE FOR SPECIFIC COGNITIVE DEFICITS IN PRECLINICAL HUNTINGTONS-DISEASE

The performance of 54 subjects genetically at risk for Huntington's di sease was examined in double-blind fashion on a series of computerized tests from the Cambridge Neuropsychological Test Automated Battery, N one of the subjects exhibited clinical movement disorder characteristi c of Huntington's disease. Of the 54 subjects, 22 mere Huntington's di sease mutation carriers and 32 were non-carriers. On a comprehensive b attery of neuropsychological tests previously shown to be sensitive to the early stages of clinical Huntington's disease, Huntington's disea se mutation carriers exhibited highly specific cognitive deficits. In particular, Huntington's disease mutation carriers performed significa ntly less well than non-carriers, matched for age and IQ, on tests of attentional set shifting and semantic verbal fluency, Furthermore, per formance on these two tests was significantly correlated, even after p artialling out the effects of age and IQ, It is suggested that these c ognitive impairments relate to a common deficit in inhibitory control mechanisms, under the control of striatofrontal mechanisms, and that s uch a deficit is present in Huntington's disease mutation carriers pri or to the onset of definite motor symptomatology, The implications for the nature of the cognitive decline seen in Huntington's disease, and possible future treatment strategies, are discussed.