Functional Competence in Alzheimer's Disease: A Novel Assessment Approach to Enhance Prediction of Risk in the Elderly

阿尔茨海默病的功能能力：一种增强老年人风险预测的新评估方法

• 批准号: 10794923
• 负责人: ANEELA RAHMAN
• 金额: $ 3.17万
• 依托单位: CUNY GRADUATE SCH AND UNIV CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10794923
• 关键词: Achievement; Activities of Daily Living; Address; Aging; Alzheimer' s Disease; Behavior; Brain; Clinical; Clinical Trials; Cognition; Cognitive; Competence; Consensus; Data; Dementia; Detection; Development; Disease; Disease Progression; Early Diagnosis; Early Intervention; Early identification; Elder Abuse; Elderly; Exhibits; Female; Functional Magnetic Resonance Imaging; Goals; High Prevalence; Household; Impaired cognition; Impairment; Independent Living; Individual; Intervention; Knowledge; Literature; Measurement; Measures; Memory; Neurodegenerative Disorders; Neuropsychology; Outcome; Outcome Assessment; Patient Care; Patients; Pattern; Performance; Persons; Pharmaceutical Preparations; Populations at Risk; Prevalence; Prevention strategy; Problem Solving; Recommendation; Research; Rest; Risk; Risk Behaviors; Safety; Scanning; Sex Differences; Symptoms; United States Food and Drug Administration; Woman; advanced disease; cognitive change; cognitive function; efficacy evaluation; executive function; functional decline; functional disability; functional improvement; functional outcomes; improved; insight; instrument; instrumental activity of daily living; interest; male; men; mild cognitive impairment; neural; neuroimaging; novel; performance based measurement; pre-clinical; prevent; risk prediction; sex; skills; symposium; treatment strategy

Project Summary/Abstract By the year 2050, as many as 16 million individuals in the US will express symptoms of Alzheimer’s disease (AD), a progressive neurodegenerative disorder marked by difficulties in memory, cognition and instrumental activities of daily living (IADL). The 2015 White House Conference on Aging emphasized a critical need for sensitive instruments to capture reduced functional capacity as a means to maximize independent living and protect older adults from exploitation and abuse. Furthermore, the Food and Drug Administration (FDA) recently recommended the measurement of subtle functional and cognitive changes during the preclinical stages as a potential global outcome to evaluate the efficacy of treatment strategies and disease modifying therapies in dementia research. However, despite the well-established importance of IADL detection, there is a lack of research on when and how functional declines first become compromised and associated brain changes along the disease spectrum. Prior research has failed to examine the emergence of subtle functional deficits during early dementia stages such as among those with subjective cognitive decline (SCD) and how such deficits advance in later stages, i.e., mild cognitive impairment (MCI), mild Alzheimer’s disease (AD). Additionally, no formal studies have assessed sex differences in terms of the neural and cognitive basis for functional abilities, considering the higher prevalence of IADL impairments in women. Given these critical gaps in the literature, our project aims to track functional decline along the AD continuum utilizing sensitive performance-based assessments, investigate sex differences and explore its association with neuroimaging data. There is growing interest in utilizing performance-based assessments in clinical trials as subtle errors in these tasks can potentially differentiate among preclinical, prodromal and more advanced disease stages. In order for clinical trials to be successful, there is a strong need to incorporate these sensitive instruments given their potential accuracy in capturing functional impairments during the preclinical or prodromal disease stages. Thus, in the proposed study, among older adults who are cognitively unimpaired and those with SCD, MCI, mild AD, we will: (1) elucidate new insights into IADL impairments during early and advanced disease stages, (2) investigate cognitive and brain changes contributing to sex differences in patterns of IADL impairments and (3) characterize the relationship between changes in functional brain networks and IADL deficits. The achievement of our stated aims will result in an improved ability to detect and identify emerging functional impairments in individuals along the AD continuum. Study findings also will contribute to our long-term goals of developing safeguards to prevent functional deficits and potential hazardous behaviors consequent to these impairments.

项目概要/摘要 到 2050 年，美国将有多达 1600 万人出现阿尔茨海默病症状 疾病（AD），一种进行性神经退行性疾病，以记忆、认知和认知困难为特征 工具性日常生活活动（IADL）。 2015 年白宫老龄化会议强调了一个关键问题 需要敏感的仪器来捕获功能能力的降低，以此作为最大限度地提高独立性的手段 生活并保护老年人免受剥削和虐待。此外，食品药品监督管理局 （FDA）最近建议测量在治疗期间微妙的功能和认知变化 临床前阶段作为评估治疗策略和疾病疗效的潜在全球结果 修改痴呆症研究中的疗法。然而，尽管 IADL 检测的重要性已得到公认， 缺乏关于功能衰退何时以及如何首先受到损害和关联的研究 大脑沿着疾病谱发生变化。先前的研究未能检验微妙的出现 痴呆早期阶段的功能缺陷，例如主观认知能力下降 (SCD) 的患者 以及这些缺陷在后期如何发展，即轻度认知障碍（MCI）、轻度阿尔茨海默病 （广告）。此外，还没有正式的研究评估神经和认知基础方面的性别差异 对于功能能力，考虑到女性 IADL 损伤的发生率较高。 鉴于文献中的这些关键空白，我们的项目旨在跟踪 AD 沿线的功能衰退 利用敏感的基于绩效的评估的连续体，调查性别差异并探索其 与神经影像数据的关联。人们越来越有兴趣利用基于绩效的评估 临床试验中这些任务中的细微错误可能会区分临床前、前驱等 疾病晚期阶段。为了使临床试验取得成功，强烈需要将 这些敏感仪器考虑到它们在捕获功能障碍方面的潜在准确性 临床前或前驱疾病阶段。因此，在拟议的研究中，在认知能力较差的老年人中 对于未受损的患者以及患有 SCD、MCI、轻度 AD 的患者，我们将：(1) 阐明关于 IADL 损伤的新见解 早期和晚期疾病阶段，(2) 研究导致性别差异的认知和大脑变化 IADL 损伤模式以及 (3) 表征大脑功能变化之间的关系 网络和 IADL 缺陷。我们既定目标的实现将导致检测和检测能力的提高 识别 AD 连续体中个体中出现的功能障碍。研究结果还将 为我们制定保障措施以防止功能性缺陷和潜力的长期目标做出贡献 这些损伤导致的危险行为。