In this prospective longitudinal study, we show that compared to controls, men with the FMR1 premutation have accelerated decline in manual dexterity and certain domains of executive functioning, including visual working memory, inhibitory control, and that conversion to FXTAS is associated with deterioration in inhibitory control, planning and problem solving, and slowing of manual movement. This evidence concerns the gene FMR1 and fragile X-associated tremor/ataxia syndrome.