Interaction of FXTAS Family History and College Degree Attainment Predicts Trajectories of Cognitive and Motor Symptoms in FMR1 Premutation Carrier Women

Abstract

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.