Abstract

OBJECTIVES To compare the neurological and psychometric characteristics of presymptomatic gene carriers and non-gene carriers who are at risk for developing Huntington's disease so as to characterise early signs of disease and to identify markers of neurological function that could be used to assess the impact of experimental therapies on the progression of disease, even among those who are clinically presymptomatic.

METHODS A sample of people at risk for Huntington's disease was genotyped and evaluated using subscales of the Wechsler adult intelligence scale–revised (WAIS-R), a quantified neurological rating scale, and computerised physiological measures including speed of movement and reaction time.

RESULTS Genotyping and clinical examination determined that 171 participants were presymptomatic gene carriers (PSGCs) and 414 participants were non-gene carriers (NGCs). The PSGCs performed significantly worse when compared with the NGCs on the digit symbol, picture arrangement, and arithmetic subscales of the WAIS-R (p<0.02) and for the physiological measures: button tapping, auditory reaction time, visual reaction time with decision, and movement time with and without decision (p<0.05). Although no PSGCs had sufficient neurological findings to warrant a diagnosis of Huntington's disease on clinical examination, the PSGCs had more frequent possible or definite abnormality for oculomotor function, chorea, muscle stretch reflexes, gait, and station stability, and rapid alternating movements (p⩽0.02).

CONCLUSIONS Among Huntington's disease gene carriers, subtle cognitive and motor deficits precede the onset of sufficient neurological abnormality to warrant a clinical diagnosis of Huntington's disease.