Functional Neuroanatomy Correlates of Worry in Older Adults

功能神经解剖学与老年人担忧的相关性

• 批准号: 9174515
• 负责人: Carmen Andreescu
• 金额: $ 42.42万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-20 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9174515
• 关键词: Age; Aging; Alzheimer' s Disease; Anisotropy; Architecture; Attention; Biological Neural Networks; Brain; Brain Pathology; Brain region; Cardiovascular system; Categories; Cognition Disorders; Cognitive; Cognitive Therapy; Communities; Data; Detection; Diagnostic and Statistical Manual of Mental Disorders; Disease; Elderly; Event; Generalized Anxiety Disorder; Half-Life; Health; Incidence; Individual; Interruption; Intervention; Investigation; Life; Longevity; Major Depressive Disorder; Measures; Mentored Patient-Oriented Research Career Development Award; Modeling; Morbidity - disease rate; National Institute of Mental Health; Nerve Degeneration; Neuroanatomy; Neurosciences; Participant; Prevention; Process; Quality of life; Reaction; Recruitment Activity; Regulation; Reporting; Research; Rest; Risk; Role; Sampling; Severities; Specificity; Stress; Stroke; Symptoms; System; Testing; Thinking; Time; White Matter Disease; White Matter Hyperintensity; Work; age related; aging brain; anxious; base; cognitive reappraisal; effective intervention; executive function; functional disability; improved; mild cognitive impairment; neuroimaging; neuromechanism; relating to nervous system; response; social anxiety; treatment choice; vascular depression

Severe worry, a transdiagnostic symptom particularly pernicious for the health of older adults, is associated with increased risk of conversion from mild cognitive impairment to Alzheimer's disease, and with increased risk of stroke and other cardiovascular events. Severe worry, defined as intense, uncontrollable worry associated with interruption in functioning and reduced quality of life, is surprisingly prevalent in the community, with 20% of older adults reporting severe worry. While there are no studies regarding the lifespan incidence of severe worry, we can draw inferences based on the incidence of Generalized Anxiety Disorder (GAD), for which up to half of the cases are late-onset. These data suggest a particularly heavy burden of severe worry loaded in the second half of life, pointing toward an increasing role for the neuropathologic changes of aging. Identifying neural mechanisms for late-life worry is a crucial step for understanding why worry crops up in the latter part of life, and for eventually improving treatment. Our team has made significant headway in this regard. Through her K23 award, which was focused on the neuroanatomy of late-life GAD, the PI has shown that neural markers of worry differ across ages. Preliminary results indicate that older worriers have impaired functional connectivity both at rest and during worry reappraisal. In addition to documenting age-related brain pathology, our preliminary findings may explain why current treatment choices, such as cognitive-behavioral therapy, which relies on worry reappraisal to interrupt the worry loop, have proven less effective in reducing worry severity in older adults and may actually be counterproductive. However, the examination of the neural architecture underlying worry has garnered relatively little attention, especially with regard to the mechanism underlying essential processes such as worry induction and reappraisal. This project will test a mechanistic model anchored in systems neuroscience and aimed at characterizing the functional neuroanatomy of severe worry in older adults. We focus on the roles of three canonical brain networks: 1) the network subserving the “resting” state, a time when many worriers would worry naturally [the Default Mode], 2) the network involved in the detection of environmentally salient, often threatening information, ideally allowing us to anchor the neural features of worry in the RDoC's threat reactivity categories [the Salience Network], and 3) the network active during cognitive efforts to reappraise worry [the Executive Control]. We will characterize the specificity of this model for aging, by testing the moderating effect of brain aging, as measured by white matter disease. The phenomenological layout of worry from everyday reactions to stress to anxious perseveration, together with the distribution of worry across various disorders, makes this investigation fit ideally within the RDoC framework. We plan to recruit a stratified sample of 160 participants (age 50 to 85) representing a wide range of worry severity. As NIMH moves away from DSM categorical disorders, identifying the neural basis of pathological transdiagnostic features, such as worry, will be of increasing importance for developing targeted interventions. 1

严重的担忧，一种对老年人健康特别有害的跨诊断症状， 从轻度认知障碍转化为阿尔茨海默病的风险增加， 中风和其他心血管事件的风险。严重担忧，定义为强烈的、无法控制的担忧 与功能中断和生活质量下降有关，在社区中令人惊讶地普遍， 有20%的老年人表示有严重的担忧。虽然没有关于寿命发生率的研究， 严重的担忧，我们可以根据广泛性焦虑症（GAD）的发病率来推断， 半数以上的病例都是迟发性的这些数据表明，严重担忧的负担特别重 在生命的后半段加载，指向衰老的神经病理学变化的作用越来越大。 确定晚年担忧的神经机制是理解为什么担忧会在大脑中突然出现的关键一步。 生命的后期，并最终改善治疗。我们的团队在这方面取得了重大进展 请注意。通过她的K23奖，这是集中在晚年GAD的神经解剖学，PI已经表明 焦虑的神经标记在不同年龄段是不同的。初步结果表明，年长的焦虑者 在休息时和重新评估忧虑时的功能连接。除了记录与年龄相关的大脑 我们的初步发现可以解释为什么目前的治疗选择，如认知行为， 依赖于重新评估担忧来中断担忧循环的治疗，已经证明在减少 担心老年人的严重性，实际上可能适得其反。然而，对神经系统的检查 作为担忧基础的体系结构相对较少受到关注，特别是在机制方面 潜在的基本过程，如担心诱导和重新评估。该项目将测试一种机械 模型锚定在系统神经科学，旨在表征功能性神经解剖严重 老年人的烦恼我们重点讨论了三个典型的大脑网络的作用：1）网络subserving “休息”状态，许多担心者自然会担心的时候[默认模式]，2）参与的网络 对环境显著的，通常是威胁性的信息的检测，理想情况下允许我们锚神经 RDoC的威胁反应性类别[显着性网络]中的担忧特征，以及3）网络活动 在重新评估担忧[执行控制]的认知努力期间。我们将描述这种特殊性 老化模型，通过测试大脑老化的调节作用，如通过白色疾病测量的。的 现象学布局的担心，从日常反应的压力，以焦虑的执着，连同 在各种疾病中的担忧分布，使这项调查理想地适合RDoC框架。 我们计划招募160名参与者（年龄50至85岁）的分层样本， 严重性。随着NIMH远离DSM分类障碍，确定病理性神经基础 转诊断特征，如担忧，对于制定有针对性的干预措施将越来越重要。 1