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

社区老年人微妙认知衰退表型的异质性

• 批准号: 10713843
• 负责人: Kelsey R Thomas
• 金额: $ 183.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713843
• 关键词: Address; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid beta-Protein; Atherosclerosis Risk in Communities; Attention; Autopsy; Baltimore; Biological Markers; Caring; Characteristics; Classification; Clinic; Clinical; Cognition; Cognitive; Communities; Data; Data Set; Dementia; Diabetes Mellitus; Diagnosis; Diagnostic Procedure; Early Diagnosis; Early Intervention; Early identification; Elderly; Fostering; Future; Genetic; Glial Fibrillary Acidic Protein; Goals; Heterogeneity; Hypertension; Impaired cognition; Impairment; Individual; Language; Light; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Memory; Memory impairment; Methods; Neuropsychological Tests; Neuropsychology; Outcome; Participant; Pathologic; Pathology; Pathway interactions; Pattern; Persons; Phase; Phenotype; Physical activity; Plasma; Populations at Risk; Prevalence; Research; Risk; Risk Reduction; Sampling; Symptoms; Thinness; Variant; Visuospatial; White Matter Hyperintensity; Work; cerebral atrophy; cognitive change; cognitive performance; cohort; dementia risk; executive function; functional decline; improved; language impairment; loved ones; middle age; mild cognitive impairment; neurofilament; personalized approach; progression risk; protective factors; recruit; resilience; secondary analysis; tau Proteins; tau-1; vascular risk factor

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.

项目总结/摘要 PA-20-185的新提交资料（NOT-AG-21-020：最大化次要分析的科学价值 现有队列和数据集，以填补研究空白， 老龄化研究的机会）。在过去的十年里，人们加大了努力，以改善早期 阿尔茨海默病和相关痴呆症（AD/ADRD）的检测，其中大部分工作集中在 病理学和生物标志物变化。然而，在我们对以下问题的理解方面仍然存在重大差距： AD/ADRD早期阶段的认知变化，尽管认知和随后的功能变化 最终对AD/ADRD患者及其亲人的生活产生最大的直接影响。 具体来说，很少有研究全面调查老年人的认知异质性， 尚未达到轻度认知障碍（MCI）的标准，但可能表现出微妙的认知困难。 这种微妙的认知下降/前MCI阶段可能是早期干预的关键机会窗口， 因此，完善我们对与AD/ADRD相关的最早认知变化的理解至关重要。 我们的工作使用数据驱动的方法来了解MCI的异质性， 除了传统的遗忘/非遗忘的区别，显示独特的模式，皮层变薄，AD 生物标志物谱和认知能力下降和进展为痴呆的比率。在这个项目中，我们将利用 来自社区动脉粥样硬化风险研究（ARIC）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或痴呆一致的认知障碍。ARIC研究和BLSA包括 从社区中招募的不同样本，这将使结果更普遍， 典型的记忆诊所样本本项目的目标包括：1）从认知表型中获得 认知未受损的老年人（即，无MCI或痴呆），使用个体的潜在特征分析 神经心理学测量，2）确定中晚期血管危险因素（糖尿病、高血压）， 身体活动水平和AD生物标志物（例如，血浆，MRI），预测成员的认知 表型组（例如，低内存、低执行等），（3）检查相关的纵向结果 与认知表型，包括进展为MCI/痴呆的比率，认知/功能障碍的比率， 下降，以及脑萎缩率和白色高信号体积变化。这项研究的结果有 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相关。确定这些独特的微妙的认知下降亚型加上相关的 生物标志物和风险/弹性特征以及进展为MCI/痴呆的风险是实现个体化的关键一步。 早期检测方法，目标是减少诊断和护理中的延误或差距。