Project Abstract The FMR1 premutation (PM) affects ~1 in 150 women and ~1 in 470 men in the United States, and can have a significant effect on physical and mental health. Forty percent of male PM carriers develop fragile X-associated tremor/ataxia syndrome (FXTAS) after the age of 50, though precisely who will manifest the disease is unknown. FXTAS is characterized by executive dysfunction, gait ataxia, and intention tremor, and it is possible that cognitive changes may affect other phenotypes, such as language. In the absence of clear markers of disease onset among male PM carriers, it is essential to characterize language in this population, which has proven to be a successful approach in related neurodegenerative disorders (e.g., Alzheimer’s). Numerous studies have demonstrated that female PM carriers differ from controls in their language (i.e., pragmatics, lexical-semantics), which has been associated with poorer executive function and reduced quality of life; however, no studies to date have examined language among male PM carriers. As a first step, the present proposal will examine language among male PM carriers across the FXTAS symptom continuum (i.e., no symptoms through severe symptoms). Without such data, this severely limits our ability to (a) fully understand the impact of the FMR1 PM, (b) examine cognitive correlates implicated in FXTAS (i.e., executive dysfunction), and (c) understand the implications of language use on quality of life. This proposal addresses these limitations with three aims: i) Examine associations between age, FXTAS-associated symptoms and pragmatic and lexical-semantic aspects of language among male PM carriers across contexts; ii) evaluate relationships with executive functioning; iii) assess interactions between language, age, and quality of life. This study will be completed virtually with a cross- sectional sample of 60 male PM carriers between the ages of 45-70 across the FXTAS symptom continuum. Males from across the U.S. will be recruited. Participants will complete virtual language elicitation and executive function tasks, as well as self-report measures of executive function and quality of life. Results from this proposal are expected to inform the relationship between language, age, and FXTAS-associated symptoms among male PM carriers. It is also expected that age-related executive dysfunction will adversely influence pragmatic and lexical-semantic language. Finally, we anticipate that reduced quality of life among older male PM carriers will adversely affect language. This proposal is consistent with the mission of the National Institutes of Health to enhance health and reduce disability by expanding our understanding of a neurodegenerative condition associated with a common genetic variant, the FMR1 PM. It also contributes to the strategic mission of the National Institute on Deafness and Other Communication Disorders by informing knowledge on the basis of language impairments among individuals w...