The relationship between striatal dopamine receptor binding and cognitive performance in Huntington's disease.
Seventeen individuals at risk for Huntington's disease and five symptomatic patients, who had previously undergone [11C]SCH23390 and [11C]raclopride PET to assess in vivo levels of striatal dopamine D1 and D2 receptor binding, had neuropsychological assessment on a series of tests known to be sensitive to symptomatic Huntington's disease, including tests of verbal fluency, memory, attention and planning. Compared with age- and IQ-matched healthy volunteers, clinically symptomatic carriers of the Huntington's disease mutation were found to be impaired on tests of verbal fluency, spatial span, planning and sequence generation, as were clinically asymptomatic Huntington's disease mutation carriers. In asymptomatic individuals, both striatal dopamine receptor levels and cognitive performance were lower in subjects approaching their estimated age of onset. In addition, performance on these tasks was found to correlate with PET measures of striatal D1 and D2 receptor binding levels, especially D2 binding. These results are consistent with a role for the striatum, as part of the complex corticobasal ganglia-thalamocortical circuitry, in the optimal scheduling and sequencing 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.
Lawrence
A D
AD
Department of Experimental Psychology, University of Cambridge, UK.
Weeks
R A
RA
Brooks
D J
DJ
Andrews
T C
TC
Watkins
L H
LH
Harding
A E
AE
Robbins
T W
TW
Sahakian
B J
BJ
D000328:Adult; D017668:Age of Onset; D001288:Attention / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism*; D004192:Discrimination, Psychological / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000523:psychology*; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D009483:Neuropsychological Tests; D011954:Receptors, Dopamine / Q000378:metabolism*; D014706:Verbal Learning / Q000502:physiology; D014796:Visual Perception / Q000502:physiology
D011954:Receptors, Dopamine