THE RELATIONSHIP BETWEEN STRIATAL DOPAMINE-RECEPTOR BINDING AND COGNITIVE PERFORMANCE IN HUNTINGTONS-DISEASE

Seventeen individuals at risk for Huntington's disease and five sympto matic patients, who had previously undergone [C-11]SCH23390 and [C-11] raclopride PET to assess in vivo levels of striatal dopamine D-1 and D -2 receptor binding, had neuropsychological assessment on a series of tests known to be sensitive to symptomatic Huntington's disease, inclu ding tests of verbal fluency, memory, attention and planning. Compared with age- and IQ-matched healthy volunteers, clinically symptomatic c arriers of the Huntington's disease mutation were found to be impaired on tests of verbal fluency, spatial span, planning and sequence gener ation, as were clinically asymptomatic Huntington's disease mutation c arriers. In asymptomatic individuals, both striatal dopamine receptor levels and cognitive performance were lower in subjects approaching th eir estimated age of onset. In addition, performance on these tasks wa s found to correlate with PET measures of striatal D-1 and D-2 recepto r binding levels, especially D-2 binding. These results are consistent with a role for the striatum, as part of the complex corticobasal gan glia-thalamocortical circuitry, in the optimal scheduling and sequenci ng of responses, and suggest that cognitive manifestations of striatal dysfunction can be evidenced in carriers of the Huntington's disease mutation prior to the onset of overt clinical movement disorder.