Table_1_Sensorimotor and inhibitory control in aging FMR1 premutation carriers.docx

Aging FMR1 premutation carriers are at risk of developing neurodegenerative disorders, including fragile X-associated tremor/ataxia syndrome (FXTAS), and there is a need to identify biomarkers that can aid in identification and treatment of these disorders. While FXTAS is more common in males than females, females can develop the disease, and some evidence suggests that patterns of impairment may differ across sexes. Few studies include females with symptoms of FXTAS, and as a result, little information is available on key phenotypes for tracking disease risk and progression in female premutation carriers. Our aim was to examine quantitative motor and cognitive traits in aging premutation carriers. We administered oculomotor tests of visually guided/reactive saccades (motor) and antisaccades (cognitive control) in 22 premutation carriers (73% female) and 32 age- and sex-matched healthy controls. Neither reactive saccade latency nor accuracy differed between groups. FMR1 premutation carriers showed increased antisaccade latencies relative to controls, both when considering males and females together and when analyzing females separately. Reduced saccade accuracy and increased antisaccade latency each were associated with more severe clinically rated neuromotor impairments. Findings indicate that together male and female premutation carriers show a reduced ability to rapidly exert volitional control over prepotent responses and that quantitative differences in oculomotor behavior, including control of visually guided and antisaccades, may track with FXTAS – related degeneration in male and female premutation carriers.老年FMR1前突变携带者（FMR1 premutation carriers）罹患神经退行性疾病的风险显著升高，此类疾病包括脆性X相关震颤/共济失调综合征（fragile X-associated tremor/ataxia syndrome, FXTAS），因此亟需筛选可辅助该类疾病诊断与治疗的生物标志物（biomarkers）。尽管FXTAS在男性中较女性更为高发，但女性同样可罹患该病，且已有证据显示不同性别间的损伤模式可能存在差异。目前鲜有研究纳入表现出FXTAS症状的女性群体，因此关于追踪女性前突变携带者疾病风险与进展的关键表型数据仍较为匮乏。本研究旨在探究老年前突变携带者的定量运动与认知特征。本研究纳入22名前突变携带者（其中女性占73%）与32名年龄、性别匹配的健康对照者，对其实施视引导/反应性扫视（saccades，运动功能）及反眼跳（认知控制）的动眼测试。两组间的反应性扫视潜伏期与准确率均无显著差异。与健康对照相比，前突变携带者的反眼跳潜伏期显著延长，无论将男性与女性合并分析还是单独分析女性群体，该差异均存在。扫视准确率降低与反眼跳潜伏期延长均与临床评估的神经运动损伤程度加重呈显著相关。研究结果表明，无论男性还是女性前突变携带者，其对优势反应快速实施意志控制的能力均有所下降；而动眼行为（包括视引导扫视与反眼跳控制）的定量差异，或可用于追踪男性与女性前突变携带者的FXTAS相关退行性病变。