Interaction of <scp>FXTAS</scp> Family History and College Degree Attainment Predicts Trajectories of Cognitive and Motor Symptoms in <scp> <i>FMR1</i> </scp> Premutation Carrier Women

The present longitudinal study focuses on FMR1 premutation carrier women during midlife and early old age (n = 115). Bringing together the genetic risk factor of a family history of FXTAS and the environmental protective factor of higher education, the goal of the study was to determine how these factors potentially interact to predict self-reported FXTAS-type symptoms in women carrying the FMR1 premutation. We investigated age-related changes in symptoms, measured prospectively over a decade. Using an accelerated longitudinal design approach, we estimated trajectories of change extending from early midlife (starting at age 39) into older age (up to age 80) in a community-based cohort. Results indicated that women with the FMR1 premutation who have a family history of FXTAS are at greater risk for experiencing symptoms during late midlife and older age than those who do not have such a family history. Consistent with research on other neurodegenerative diseases, this family history risk may be moderated by completing a college education, suggesting that cognitive enrichment during a period of neuroplasticity might provide protection from the neurodegenerative symptoms that are experienced by some women with the premutation as they age.