The primary cognitive deficit among males with fragile X-associated tremor/ataxia syndrome (FXTAS) is a dysexecutive syndrome

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with a premutation trinucleotide repeat expansion in the fragile X mental retardation 1 gene. Symptoms include gait ataxia, action tremor, and cognitive impairment. The objectives of the study were to clarify the nature of the dysexecutive syndrome observed in FXTAS and to assess the contribution of executive impairment to deficits in nonexecutive cognitive functions. Compared to controls, men with FXTAS demonstrated significant executive impairment, which was found to mediate group differences in most other cognitive abilities. Asymptomatic premutation carriers performed similarly to controls on all but two measures of executive functioning. These findings suggest that the impairment of nonexecutive cognitive skills in FXTAS is in large part secondary to executive dysfunction.

Keywords:

• Fragile X
• Premutation
• Cognition disorders
• Trinucleotide repeats
• Executive cognitive function

Primary funding for this study was provided by the National Institute of Neurological Disorders and Stroke (NINDS; Grant NS044299, J. Grigsby). We would like to express our gratitude to the study participants and their families for participating in this study.