PROJECT SUMMARY/ABSTRACT
The current study will examine attention and the respective involved attentional subsystems among children
and adult female carriers of the fragile X premutation allele (PM). The goals are to: 1) provide information
about attentional subsystems and its presentation in this population; 2) examine whether there are age-related
changes; and 3) investigate biological contributions to attention. In the US, approximately 1.5 million people
carry a PM, defined as 55-200 expanded CGG repeats in the X-linked FMR1 gene. PM carriers do not have
fragile X syndrome but they are at increased risk for fragile X-associated disorders in adulthood. Women with a
PM are at risk for Fragile X-Associated Primary Ovarian Insufficiency, higher rates of mental health disorders
and reported attention problems, and a late-life progressive neurodegenerative disorder, Fragile X
Tremor/Ataxia Syndrome. No detailed examination of attentional subsystems exists in this population, but the
possibility that underlying subtle changes in attention may reflect an etiology-specific phenotype and/or later
cognitive and behavioral presentations is intriguing. To date, findings reported on performance-based
measures of attention are inconclusive in PM women and lacking in PM girls. Via cross-sectional analysis of
two cohorts, PM women and PM girls, each with an age-matched control group, the study will investigate
whether mild, yet discernable, attention deficits are present in these cohorts using the Attention Network Test
(ANT) and behavioral questionnaires. The ANT is a well-established, sensitive, cognitive task designed to
measure the three attention networks of alerting, orienting and executive control. Intrasubject variability of
reaction time on the ANT will also be calculated as a predictor of real-life outcomes. Preliminary studies led by
the applicant with neurotypical children and PM women indicated that intrasubject variability is associated with
reported attention and executive function problems while reaction time is not, supporting the utility of
intrasubject variability to potentially bridge discrepancies between performance and reports. Behavioral
characteristics of attention will be measured with self-reports for women and girls, and additional parent-reports
for girls. This project will determine whether 1) women with a PM and 2) girls with a PM have an increased risk
of attention problems compared to controls as determined with the ANT and standardized questionnaires; 3)
whether cross sectional evaluation of attention problems shows evidence of worsening from childhood to
adulthood in females with a PM; and 4) whether PM-related biological factors are associated with attentional
outcomes in female PM carriers. Results will provide a rigorous assessment of the attentional profile in female
children and adults with a PM. Facilitating detection of attention deficits in childhood and determining how
these deficits manifest in adulthood may offer insight into a subtle underlying cognitive profile associated with a
PM, allow for examination for potential age-related cognitive changes that might be associated with possible
later risk, and provide a foundation for targeted and preventative interventions to enhance quality of life.
