Evidence for specific cognitive deficits in preclinical Huntington's disease

• Published in: Brain (London, England : 1878) England : 1878), 1998-07, Vol.121 (7), p.1329-1341
• Main Authors: LAWRENCE, A. D, HODGES, J. R, ROSSER, A. E, KERSHAW, A, FFRENCH-CONSTANT, C, RUBINSZTEIN, D. C, ROBBINS, T. W, SAHAKIAN, B. J
• Format: Article
• Language: English
• Subjects: Adult; Attention - physiology; Biological and medical sciences; Cognition Disorders - diagnosis; Cognition Disorders - etiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Discrimination (Psychology) - physiology; Female; Humans; Huntington Disease - complications; Huntington Disease - physiopathology; Huntington Disease - psychology; Learning - physiology; Male; Medical sciences; Memory - physiology; Middle Aged; Motor Activity - physiology; Neurology; Pattern Recognition, Visual - physiology; Psychometrics - methods; Reaction Time - physiology; Space Perception - physiology; Visual Perception - physiology
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/121.7.1329

The performance of 54 subjects genetically at risk for Huntington's disease was examined in double-blind fashion on a series of computerized tests from the Cambridge Neuropsychological Test Automated Battery. None of the subjects exhibited clinical movement disorder characteristic of Huntington's disease. Of the 54 subjects, 22 were Huntington's disease mutation carriers and 32 were non-carriers. On a comprehensive battery of neuropsychological tests previously shown to be sensitive to the early stages of clinical Huntington's disease, Huntington's disease mutation carriers exhibited highly specific cognitive deficits. In particular, Huntington's disease mutation carriers performed significantly less well than non-carriers, matched for age and IQ, on tests of attentional set shifting and semantic verbal fluency. Furthermore, performance on these two tests was significantly correlated, even after partialling out the effects of age and IQ. It is suggested that these cognitive impairments relate to a common deficit in inhibitory control mechanisms, under the control of striatofrontal mechanisms, and that such a deficit is present in Huntington's disease mutation carriers prior 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.