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Sandra Close Kirkwood, MS; Eric Siemers, MD; Julie C. Stout, PhD; M. E. Hodes, MD, PhD; P. Michael Conneally, PhD; Joe C. Christian, MD, PhD; Tatiana Foroud, PhD

Arch Neurol. 1999;56:563-568.

Objective  To determine whether longitudinal changes in cognitive and motor function can be detected among clinically presymptomatic individuals carrying the Huntington disease (HD) allele.

Design  A longitudinal, case-control, double-blind study comparing presymptomatic gene carriers and non–gene carriers at risk for HD examined an average of 3.7 years apart.

Setting  The Department of Medical and Molecular Genetics at a general clinic research center in Indianapolis, Ind.

Participants  A sample of 43 at-risk individuals consisting of presymptomatic gene carriers (n=12) and non–gene carriers (n=31).

Measures  Huntington disease gene status was determined by molecular testing of the HD gene. Subscales from the Wechsler Adult Intelligence Scale–Revised and a quantified neurologic rating scale were administered.

Results  Scores on the digit symbol subscale of the Wechsler Adult Intelligence Scale–Revised (P<.05) and 2 neurologic variables—optokinetic nystagmus (P<.01) and rapid alternating movements (P<.005)—declined more rapidly among presymptomatic gene carriers than among non–gene carriers. At follow-up examination, compared with non–gene carriers, presymptomatic gene carriers had significantly lower scores on the digit symbol subscale (P=.02) and for 4 neurologic variables—rapid alternating movements (P<.005), optokinetic nystagmus (P<.001), overall ocular movements (P<.02), and chorea of the trunk (P<.02).

Conclusions  Psychomotor speed, optokinetic nystagmus, and rapid alternating movements demonstrated significant decline early in the pathological process of HD. These results suggest that subtle worsening of psychomotor, oculomotor, and motor functions occurs before the onset of signs sufficient to make a clinical diagnosis in individuals who have inherited the HD allele.

From the Departments of Medical and Molecular Genetics (Ms Kirkwood and Drs Hodes, Conneally, Christian, and Foroud) and Neurology (Drs Siemers and Conneally), Indiana University School of Medicine, Indianapolis; and the Department of Psychology, Indiana University, Bloomington (Dr Stout).

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