Intraindividual Cognitive Variability as an Early Marker of Alzheimer's Disease

个体内认知变异是阿尔茨海默病的早期标志

• 批准号: 10672436
• 负责人: Andrea Weinstein
• 金额: $ 18.33万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672436
• 关键词: Age; Alzheimer' s Disease; Alzheimer' s disease pathology; Amyloid beta-Protein; Assessment tool; Behavior; Biological; Cellular Phone; Clinical; Cognition; Cognitive; Cohort Studies; Controlled Environment; Data; Dementia; Deposition; Detection; Development; Disease; Early Diagnosis; Early identification; Ecological momentary assessment; Elderly; Feeling; Foundations; Goals; Hippocampus; Image; Impaired cognition; Individual; Interpersonal Relations; Intervention; Knowledge; Life; Loneliness; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mentored Patient-Oriented Research Career Development Award; Moods; Nerve Degeneration; Neuropsychological Tests; Neuropsychology; Oranges; Participant; Pattern; Performance; Persons; Positron-Emission Tomography; Prevention; Protocols documentation; Psychosocial Factor; Reporting; Research; Research Personnel; Resistance; Risk; Risk Factors; Sampling; Signal Transduction; Social Interaction; Social support; Stress; Symptoms; Technology; Testing; Time; Training; cognitive capacity; cognitive change; cognitive function; cognitive performance; cognitive testing; contextual factors; cost effective; early detection biomarkers; health assessment; improved; individual variation; mHealth; mortality; neuroimaging; neuropathology; novel strategies; performance tests; physical state; pre-clinical; programs; psychologic; psychosocial; recruit; resilience; resilience factor; skills; social engagement; symptomatology; tau Proteins; tool

ABSTRACT Alzheimer’s disease (AD) is the most common form of dementia, with neuropathology such as beta- amyloid (Aβ) deposits and reduced hippocampal volume developing years before clinical cognitive impairment. Early identification of these preclinical AD stages is imperative for improving prevention and treatment efforts. Unfortunately, capturing the earliest subtle cognitive changes is difficult with traditional neuropsychological tests, which 1) were developed to detect overt clinical cognitive impairment, and 2) measure peak performance at a single, and potentially non-representative, time point in a well-controlled environment that is detached from daily life. These limitations underscore the need for valid assessment tools that capture not only the range of everyday cognition but also aspects of daily life, such as psychosocial factors, that signal resilience to AD clinical symptomatology. Mobile health (mHealth) assessments that utilize common smartphone technology may help overcome these limitations by sampling behavior multiple times per day in ‘real-time’, over the course of several days. Repeated sampling enables characterization of the time-course of a person’s behavior, both in terms of their cognition and their psychosocial context. The goal of this proposal is to examine the utility of a mHealth program to detect early markers of AD cognitive vulnerability. The specific aims are to examine whether variability over time on mHealth cognitive measures (i.e., intraindividual cognitive variability) is 1) a signature of AD neuropathologic risk, and 2) predicts longitudinal cognitive decline on traditional neuropsychological tests. An exploratory aim proposes to examine whether individuals with more AD neuropathology show stronger synchrony between their everyday psychosocial context (interpersonal interactions, mood, loneliness) and everyday cognitive performance. Participants will be cognitively normal Aβ positive and negative individuals recruited from ongoing longitudinal studies that gather neuropsychological and neuroimaging (PET, MRI) markers of AD neuropathology. Participants will undergo a 14-day mHealth protocol, twice over two years, that samples psychosocial factors and cognitive performance. The proposed training aims include 1) building foundational mHealth skills and specific expertise in using mHealth to measure cognition and psychosocial factors, 2) acquiring advanced expertise in psychosocial factors that contribute to resistance and resilience to AD symptoms, and 3) developing in-depth knowledge of PET and MRI imaging of AD neuropathologic risk factors. In summary, this proposed K23 award sets the foundation toward understanding whether individuals at high AD neuropathologic risk show early markers of cognitive vulnerability on mHealth assessments. The results of this study will establish the necessary groundwork for the PI’s development as an independent neuropsychologist-investigator using cutting-edge approaches for early identification of risk and resiliency factors that influence AD symptom development, and ultimately, AD treatment.

摘要 阿尔茨海默氏病（AD）是最常见的痴呆形式，具有神经病理学，如β-淀粉样蛋白， 淀粉样蛋白（Aβ）沉积和海马体积减少，在临床认知障碍前数年发展。 早期识别这些临床前AD阶段对于改善预防和治疗工作至关重要。 不幸的是，传统的神经心理学很难捕捉最早的微妙认知变化 测试，1）开发用于检测明显的临床认知障碍，2）测量峰值性能 在一个单独的，可能不具有代表性的时间点，在一个良好控制的环境中， 日常生活这些局限性突出表明，需要有效的评估工具，不仅要捕捉 日常认知，以及日常生活的各个方面，如心理社会因素，这些因素表明对AD的适应能力 临床病理学利用常见智能手机技术的移动的健康（mHealth）评估 通过在整个过程中每天多次“实时”地对行为进行采样， 好几天了重复采样能够表征一个人行为的时间过程， 他们的认知和心理社会背景。 本提案的目的是检查移动健康计划的实用性，以检测AD的早期标志物 认知脆弱性具体的目的是检查是否随着时间的变化对mHealth认知 措施（即，个体内认知变异性）是1）AD神经病理风险的标志，以及2）预测 传统神经心理学测试的纵向认知能力下降。一个探索性的目标是研究 AD神经病理学程度较高的个体是否在日常生活中表现出更强的同步性， 社会心理环境（人际互动、情绪、孤独）和日常认知表现。 参与者将是从正在进行的纵向研究中招募的认知正常的Aβ阳性和阴性个体。 收集AD神经病理学的神经心理学和神经影像学（PET，MRI）标记物的研究。 参与者将接受为期14天的mHealth协议，两年两次，对心理社会因素进行采样 和认知能力。拟议的培训目标包括：1）建立基本的移动健康技能， 在使用mHealth测量认知和心理社会因素的具体专业知识，2）获得先进的 在有助于抵抗和恢复AD症状的心理社会因素方面的专业知识，以及3） 深入了解AD神经病理危险因素的PET和MRI成像。 总而言之，这项拟议的K23奖项为了解个人是否在 高AD神经病理风险显示了mHealth评估中认知脆弱性的早期标志。的 这项研究的结果将建立必要的基础，为PI的发展，作为一个独立的 神经心理学家-使用尖端方法进行风险和弹性早期识别的调查员 影响AD症状发展的因素，并最终影响AD治疗。