The Autistic Brain Over 45: The Anatomic, Functional, and Cognitive Phenotype

项目摘要 对成人自闭症患者的神经和认知变化或长期预后知之甚少。 谱系障碍(ASD)年龄超过50岁，尽管仅在美国就有数十万 自闭症患者将在未来几十年达到这个年龄段。横断面研究结果表明，新的 认知、感觉运动和精神健康问题出现，脑组织加速丢失。 功能和结构的大脑连接也受到影响，如静息状态功能磁共振和 弥散磁共振成像。 该项目旨在描述ASD患者中老年脑解剖和功能的轨迹。 以及认知和行为变化，并确定预测不良结果的风险因素，包括 GABA浓度下降和兴奋性的可疑影响：衰老中的抑制失衡。建议数 更新将利用40-70岁ASD患者和匹配的典型ASD患者的现有队列(队列1) 比较(TC)参与者。此外，由50名ASD患者和70名TC患者组成的新队列(队列2) 年龄在40-70岁的参与者将被招募。将对这两个队列进行纵向跟踪，每隔一年收集数据 3.5-5年。将在每个时间点获取大量数据，包括多模式核磁共振扫描、测量 磁共振波谱、诊断、认知和行为评估的GABA浓度以及 病史和个人病史信息。 该项目将追求3个具体目标。目标1将确定以下方面的更改(和更改的变化率) 大脑解剖、功能和连通性，并将这些与3个可疑风险领域的行为变化联系起来 运动、执行和情感功能。目标2将测试群体差异和年龄对GABA的影响 集中以及网络整合和隔离。目标3将确定行为和神经风险因素 不良(或积极)结果(例如，不良适应行为量表、日常生活技能丧失)使用 机器学习，并根据GABA水平、不同的变化率或 差异域专一性。

Project Summary Extremely little is known about neural and cognitive changes or long-term prognosis for adults with autism spectrum disorders (ASD) older than 50 years of age, although in the US alone hundreds of thousands of people with ASD will reach this age group in the coming decades. Cross-sectional findings suggest that new cognitive, sensorimotor, and mental health problems emerge and that accelerated brain tissue loss occurs. Functional and structural brain connectivity is also affected, as shown with resting state functional MRI and diffusion MRI. This project aims to characterize mid- to late-life trajectories of brain anatomy and function in ASD, as well as cognitive and behavioral change, and identify risk factors that predict poor outcomes including suspected effects of declining GABA concentrations and excitatory:inhibitory imbalance in aging. The proposed renewal will leverage an existing cohort (Cohort 1) of 40-70 year olds with ASD and matched typical comparison (TC) participants. In addition, a new cohort (Cohort 2) of 50 individuals with ASD and 70 TC participants age 40-70 will be recruited. Both cohorts will be followed longitudinally, with data collection every 3.5-5 years. Extensive data will be acquired at each time-point, including multimodal MRI scans, measures of GABA concentration from MR spectroscopy, diagnostic, cognitive, and behavioral assessments, as well as medical and personal history information. The project will pursue 3 specific aims. Aims 1 will identify alterations (and altered rates of change) in brain anatomy, function, and connectivity and relate these to behavioral changes in 3 suspected risk domains of Motor, Executive, and Affective function. Aim 2 will test for group differences and effects of age in GABA concentrations and in network integration and segregation. Aim 3 will identify behavioral and neural risk factors of adverse (or positive) outcomes (e.g. on scales of maladaptive behavior, loss of daily living skills) using machine learning, and identify ASD subgroups based on GABA levels, differential rates of change, or differential domain-specificity.