Effects of Healthy Aging and Mild Cognitive Impairment on Memory Representations

健康老龄化和轻度认知障碍对记忆表征的影响

• 批准号: 10211437
• 负责人: Roberto Cabeza
• 金额: $ 226.11万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10211437
• 关键词: Affect; Age-associated memory impairment; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Anterior; Attention; Attentional deficit; Attenuated; Binding; Categories; Cognitive deficits; Complex; Cues; Dementia; Development; Diagnosis; Disease; Dissociation; Early Diagnosis; Elderly; Episodic memory; Event; Functional Magnetic Resonance Imaging; Functional disorder; Impairment; Individual; Knowledge; Link; Measures; Medial; Memory; Memory impairment; Methods; Names; Participant; Perception; Phase; Population; Probability; Process; Retrieval; Role; Semantics; Sensory; Stimulus; Sum; Temporal Lobe; Testing; Time; Training; Vision; Visual; Visual Pathways; Visual impairment; amnestic mild cognitive impairment; cognitive ability; cognitive function; cognitive process; experience; healthy aging; memory process; mild cognitive impairment; neural correlate; neuromechanism; novel; pathological aging; preservation; programs; semantic processing; visual memory; visual stimulus; young adult

Alzheimer’s Disease (AD) impairs not only cognitive abilities, such as memory, but also sensory functions, such as vision. The current project investigates memory-vision interactions in the early stage of AD known as amnestic Mild Cognitive Impairment (aMCI), as well as in healthy aging. We focus on memory for visual stimuli, which declines substantially in AD, predicting dementia more than a decade before diagnosis. We propose 3 functional MRI (fRMI) studies, each including 3 groups of participants: aMCI, older adults, and younger adults. Whereas most fMRI studies on memory and aMCI investigated memory processes, we focus on the quality of the information used by these processes or memory representations. To our knowledge, no fMRI study has examined the quality of memory representations in MCI. Our first aim is to investigate the effects of healthy aging and aMCI on visual vs. semantic features of memory representations. There is evidence that healthy aging impairs visual representations in posterior occipito-temporal cortex (OTC) and medial temporal lobe (MTL) regions, but we have preliminary that it spares semantic representations in anterior OTC/MTL. In contrast, aMCIs are impaired in semantic processing and anterior temporal function. We test the hypothesis that visual representations in posterior OTC/MTL are impaired in both aMCI and healthy older adults, whereas semantic representations in anterior OTC/MTL are impaired in aMCI but not in healthy older adults (Hypothesis 1). This dissociation between healthy and pathological aging has important implications for the early diagnosis of AD. Our second aim is to examine the semantic support effect on memory representations in healthy older adults and aMCIs. The semantic support effect refers to the reliable finding that conditions that allow or promote the use of preexistent semantic knowledge tend to attenuate age-related cognitive deficits, including memory deficits. The semantic support effect is weaker in aMCIs, consistent with their semantic processing deficits. Each of the 3 studies investigates a different form of the semantic support effect (levels of processing, schema congruency, and conceptual attention). We test the hypothesis that the semantic support effect enhances the quality of visual memory representations and subsequent visual memory to a greater extent in healthy older adults than in aMCIs (Hypothesis 2). This finding has implications for the use of the semantic support in memory training in these populations. In sum, the proposed studies will systematically examine the neural mechanisms of visual memory deficits in MCI and healthy aging. They will use novel representational similarity analyses that have not been used yet to investigate memory representations in aMCI. The expected results will contribute to methods for diagnosing AD early in the disease and to rehabilitating memory in aMCI and healthy aging, and are hence, highly significant.

阿尔茨海默病（AD）不仅损害认知能力，如记忆，还损害感觉功能，如视觉。目前的项目调查了阿尔茨海默病早期的记忆-视觉相互作用，即遗忘性轻度认知障碍（aMCI），以及健康衰老。我们关注的是对视觉刺激的记忆，这种记忆在阿尔茨海默氏症中显著下降，在诊断前十多年就可以预测痴呆症。我们提出3个功能性MRI （fRMI）研究，每个研究包括3组参与者：aMCI、老年人和年轻人。虽然大多数关于记忆和aMCI的fMRI研究调查了记忆过程，但我们关注的是这些过程或记忆表征所使用的信息的质量。据我们所知，目前还没有fMRI研究检测MCI中记忆表征的质量。我们的第一个目的是研究健康老化和aMCI对记忆表征的视觉和语义特征的影响。健康衰老对后枕颞叶（OTC）和内侧颞叶（MTL）的视觉表征有影响，但对前枕颞叶/内侧颞叶的语义表征没有影响。相反，amci在语义加工和前颞叶功能上受损。我们检验了在aMCI和健康老年人中，OTC/MTL后部的视觉表征受损，而在aMCI中，OTC/MTL前部的语义表征受损，但在健康老年人中没有（假设1）。这种健康衰老和病理性衰老之间的分离对阿尔茨海默病的早期诊断具有重要意义。我们的第二个目的是研究语义支持对健康老年人和非能动者记忆表征的影响。语义支持效应是指一个可靠的发现，即允许或促进使用先前存在的语义知识的条件往往会减弱与年龄相关的认知缺陷，包括记忆缺陷。语义支持效应较弱，与语义加工缺陷一致。这3项研究分别研究了不同形式的语义支持效应（加工水平、图式一致性和概念注意）。我们验证了语义支持效应在健康老年人中比在amci中更大程度上提高视觉记忆表征和随后视觉记忆的质量（假设2）。这一发现对在这些人群中使用语义支持进行记忆训练具有启示意义。综上所述，本研究将系统地探讨MCI中视觉记忆缺陷与健康衰老的神经机制。他们将使用新颖的表征相似性分析，尚未用于研究aMCI中的记忆表征。预期的结果将有助于在疾病早期诊断AD的方法，以及在aMCI中恢复记忆和健康衰老，因此具有重要意义。