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

项目摘要/摘要 到2050年，美国将有多达1600万人出现阿尔茨海默氏症的症状 阿尔茨海默病(AD)是一种进行性神经退行性疾病，以记忆、认知和 日常生活工具性活动(IADL)。2015年白宫老龄问题会议强调了一个关键的 需要敏感的仪器来捕捉减少的功能能力，以此作为最大化独立的一种手段 保护老年人不受剥削和虐待。此外，美国食品和药物管理局 (FDA)最近建议对 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治疗方法。然而，尽管IADL检测的重要性是公认的， 缺乏关于功能性衰退何时以及如何首次出现损害并与之相关的研究 大脑随着疾病谱的变化而变化。先前的研究未能检验出微妙的 早期痴呆阶段的功能缺陷，例如主观认知功能下降(SCD)的人 以及这种缺陷在后期是如何发展的，即轻度认知障碍(MCI)、轻度阿尔茨海默病 (Ad)。此外，还没有正式的研究从神经和认知基础方面评估性别差异。 在功能能力方面，考虑到IADL障碍在女性中的较高患病率。 考虑到文献中的这些关键差距，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，调查性别差异并探索其 与神经影像数据的关联。越来越多的人对利用绩效评估在 临床试验作为这些任务中的细微错误，可能会区分临床前、前驱症状和更多 疾病晚期。为了使临床试验取得成功，有强烈的需要将 这些灵敏的仪器在捕捉功能障碍方面具有潜在的准确性。 临床前或前驱疾病阶段。因此，在拟议的研究中，在认知能力较强的老年人中 未受损的人和患有SCD、MCI、轻度AD的人，我们将：(1)阐明对IADL障碍的新见解 疾病早期和晚期，(2)调查导致性别差异的认知和大脑变化 IADL损害的模式和(3)描述脑功能改变之间的关系 网络和IADL赤字。我们所宣布的目标的实现将导致提高检测和 找出AD过程中出现的新的功能障碍。研究结果也将 为我们制定保障措施的长期目标做出贡献，以防止功能缺陷和潜在的 因这些损伤而产生的危险行为。

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.