Ten-year rate of longitudinal change in neurocognitive and motor function in prediagnosis Huntington disease†

Longitudinal studies of neurocognitive function in prediagnosis Huntington disease (pre-HD) have been few, and duration of follow-up has been brief. In the current study, 155 individuals at-risk for HD completed a battery of cognitive and motor tasks at two study visits approximately 10 years apart. Participants were classified as: 1) at-risk, without the CAG expansion (normal controls, NC; n = 112), or 2) CAG expanded (CAG+; n = 43). To examine the rate of decline at different stages of the pre-HD period, participants in the CAG+ group were further characterized as converters (i.e., individuals who developed manifest HD over the course of the study; n = 21) or nonconverters (n = 22), and their performances were compared. The CAG+ group exhibited faster rates of neurocognitive decline over the course of the study, relative to the NC group. In addition, more rapid decline was associated with closer proximity to estimated age of disease onset in the CAG+ group. Faster rates of motor and psychomotor decline were observed in the CAG+ converter group, relative to the nonconverters. These findings suggest that neurocognitive decline in pre-HD, particularly in motor and psychomotor domains, begins insidiously and accelerates as individuals approach disease onset.