Heterogeneity of subtle cognitive decline phenotypes in community-dwelling older adults

项目摘要/摘要 PA-20-185的新提交(NOT-AG-21-020：使二次分析的科学价值最大化 现有的队列和数据集，以弥补研究差距并培养更多 老龄化研究中的机会)。在过去的十年里，人们加大了努力，以便及早改善 阿尔茨海默病和相关痴呆的检测(AD/ADRD)，这些努力大多集中在 病理和生物标志物改变。然而，在我们对以下问题的理解上仍然存在严重差距 AD/ADRD早期阶段的认知改变，尽管认知和随后的功能改变 最终对AD/ADRD患者及其亲人的生活产生最大的直接影响。 具体地说，很少有工作全面调查老年人的认知异质性 尚不符合轻度认知障碍(MCI)的标准，但可能表现出微妙的认知困难。 这一微妙的认知功能下降/MCI前期阶段可能是早期干预和 因此，完善我们对与AD/ADRD相关的最早认知变化的理解是至关重要的。 我们使用数据驱动的方法来理解MCI的异构性的工作显示了特定的子类型 除了表现出独特的皮质变薄模式的传统遗忘性/非遗忘性区别外，AD 生物标记物概况，以及认知衰退和发展为痴呆症的比率。在这个项目中，我们将利用 来自社区动脉粥样硬化风险(ARIC)研究和巴尔的摩纵向研究的丰富纵向数据 老龄化研究(BLSA)，并使用数据驱动的方法来表征老年人的认知异质性 他们还没有表现出与MCI或痴呆症一致的认知障碍。ARIC研究和BLSA包括 从社区中招募不同的样本，这将允许更广泛地推广结果 典型的记忆诊所样本。本项目的目标包括：1)在 认知正常的老年人(即无MCI或痴呆症)使用个体潜伏期分析 神经心理测量，2)确定中老年血管危险因素(糖尿病、高血压)， 体力活动水平和预测认知能力的AD生物标志物(如血浆、核磁共振) 表型组(例如，低记忆力、低执行力等)，以及3)检查相关的纵向结果 与认知表型，包括进展到MCI/痴呆的比率，认知/功能比率 下降，并出现脑萎缩和脑白质高信号体积改变。这项研究的结果是 提高我们对最早出现的认知特征类型的理解的潜力 与AD/ADRD关联。确定这些独特的微妙认知衰退亚型加上相关的 生物标志物和风险/恢复力特征以及进展为MCI/痴呆的风险是迈向个体化的关键一步 早期发现的方法，目的是减少诊断和护理方面的延误或差距。

PROJECT SUMMARY/ABSTRACT New submission for PA-20-185 (NOT-AG-21-020: Maximizing the Scientific Value of Secondary Analyses of Existing Cohorts and Datasets in Order to Address Research Gaps and Foster Additional Opportunities in Aging Research). Over the last decade, there have been increased efforts to improve early detection of Alzheimer’s disease and related dementias (AD/ADRD), with most of these efforts focused on pathological and biomarker changes. However, there also continues to be critical gaps in our understanding of cognitive changes in the early stages of AD/ADRD, despite cognitive and subsequent functional changes ultimately having the greatest direct impact on the lives of people living with AD/ADRD and their loved ones. Specifically, little work has comprehensively investigated the cognitive heterogeneity within older adults who do not yet meet criteria for mild cognitive impairment (MCI), but who may be showing subtle cognitive difficulties. This subtle cognitive decline/pre-MCI phase may be a critical window of opportunity for early intervention and planning, so refining our understanding of the earliest cognitive changes associated with AD/ADRD is crucial. Our work using a data-driven approach to understand the heterogeneity of MCI has shown specific subtypes beyond the traditional amnestic/non-amnestic distinction that show unique patterns of cortical thinning, AD biomarker profiles, and rates of cognitive decline and progression to dementia. In this project, we will leverage the rich longitudinal data from the Atherosclerosis Risk in Communities (ARIC) Study and Baltimore Longitudinal Study of Aging (BLSA) and use a data-driven approach to characterize the cognitive heterogeneity in older adults who do not yet show cognitive impairments consistent with MCI or dementia. The ARIC Study and BLSA include diverse samples recruited from the community, which will allow for greater generalization of results beyond the typical memory clinic samples. The aims of this project include: 1) Derive cognitive phenotypes among cognitively unimpaired older adults (i.e., no MCI or dementia) using latent profile analysis of individual neuropsychological measures, 2) Determine the mid- and late-life vascular risk factors (diabetes, hypertension), physical activity levels, and AD biomarkers (e.g., plasma, MRI) that predict membership to the cognitive phenotype groups (e.g., low-memory, low-executive, etc.), and 3) Examine the longitudinal outcomes associated with the cognitive phenotypes, including rates of progression to MCI/dementia, rates of cognitive/functional decline, and rates of brain atrophy and white matter hyperintensity volume changes. Results from this study have the potential to improve our understanding of the types of cognitive profiles that emerge as the earliest changes associated with AD/ADRD. Determining these unique subtle cognitive decline subtypes plus associated biomarker and risk/resilience profiles and risk of progression to MCI/dementia is a key step toward individualized approaches to early detection with the goal of reducing delays or gaps in diagnosis and care.