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

项目总结/摘要 到2050年，美国将有多达1600万人表现出阿尔茨海默氏症的症状。 AD是一种进行性神经退行性疾病，其特征在于记忆、认知和行为障碍。 工具性日常生活活动（IADL）2015年白宫老龄问题会议强调， 需要敏感的仪器来捕捉功能降低的情况，作为最大限度地独立 保护老年人免受剥削和虐待。此外，食品和药物管理局 (FDA)最近建议测量的微妙的功能和认知变化， 临床前阶段作为评价治疗策略和疾病疗效的潜在全球结局 痴呆症研究中的改良疗法。然而，尽管IADL检测的重要性已经得到了很好的证实， 缺乏关于功能衰退何时以及如何开始受到损害和相关的研究。 大脑会随着疾病谱沿着变化先前的研究未能研究微妙的 痴呆早期阶段的功能缺陷，如主观认知下降（SCD） 以及这些缺陷在后期阶段如何发展，即，轻度认知障碍（MCI），轻度阿尔茨海默病 （AD）。此外，没有正式的研究评估神经和认知基础方面的性别差异 考虑到女性IADL障碍的患病率较高， 鉴于这些文献中的关键差距，我们的项目旨在跟踪功能下降沿着AD 连续使用敏感的基于性能的评估，调查性别差异，并探讨其 与神经影像学数据的关联。越来越多的人对利用基于绩效的评估感兴趣， 临床试验，因为这些任务中的细微错误可能会在临床前、前驱期和更多 疾病晚期。为了使临床试验取得成功， 这些敏感的仪器在捕获功能障碍的过程中具有潜在的准确性 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， 未受损和SCD，MCI，轻度AD，我们将：（1）阐明新的见解IADL损伤期间 早期和晚期疾病阶段，（2）调查认知和大脑变化导致的性别差异 在IADL损伤的模式和（3）表征脑功能变化之间的关系 网络和IADL缺陷。实现我们的既定目标将导致提高检测能力， 识别个体沿着AD连续体出现的功能障碍。研究结果还将 有助于我们制定保障措施，以防止功能缺陷和潜在的长期目标， 危险行为的后果，这些缺陷。

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.