Longitudinal cognitive and motor changes among presymptomatic Huntington disease gene carriers

Objective: To determine whether longitudinal changes in cognitive and motor function can be detected among clinically presymptomatic individuals carry ing the Huntington disease (HD) allele. Design: A longitudinal, case-control, double-blind study comparing presympt omatic gene carriers and non-gene carriers at risk for HD examined an avera ge of 3.7 years apart. Setting: The Department of Medical and Molecular Genetics at a general clin ic research center in Indianapolis, Ind. Participants: A sample of 43 at-risk individuals consisting of presymptomat ic gene carriers (n = 12) and non-gene carriers (n = 31). Measures: Huntington disease gene status was determined by molecular testin g of the HD gene. Subscales from the Wechsler Adult Intelligence Scale-Revi sed and a quantified neurologic rating scale were administered. Results: Scores on the digit symbol subscale of the Wechsler Adult Intellig ence Scale-Revised (P < .05) and 2 neurologic variables-optokinetic nystagm us (P < .01) and rapid alternating movements (P < .005)-declined more rapid ly among presymptomatic gene carriers than among non-gene carriers. At foll ow-up examination, compared with non-gene carriers, presymptomatic gene car riers had significantly lower scores on the digit symbol subscale (P = .02) and for 4 neurologic variables-rapid alternating movements (P < .005), opt okinetic nystagmus (P < .001), overall ocular movements (P < .02), and chor ea of the trunk (P < .02). Conclusions: Psychomotor speed, optokinetic nystagmus, and rapid alternatin g movements demonstrated significant decline early in the pathological proc ess of HD. These results suggest that subtle worsening of psychomotor, ocul omotor, and motor functions occurs before the onset of signs sufficient to make a clinical diagnosis in individuals who have inherited the HD allele.