Deficits in top-down processes during episodic memory in aging and preclinical AD

衰老和临床前 AD 情景记忆过程中自上而下过程的缺陷

• 批准号: 8580524
• 负责人: ELIZABETH MORMINO
• 金额: $ 5.07万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8580524
• 关键词: Aging; Alzheimer' s Disease; Amyloid beta-Protein; Attention; Behavior; Brain; Brain region; Categories; Clinical; Cognitive aging; Cues; Dementia; Deposition; Elderly; Episodic memory; Etiology; Event; Face; Female; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Impaired cognition; Individual; Laboratories; Light; Magnetic Resonance Imaging; Measures; Medial; Mediating; Memory; Names; Nerve Degeneration; Neuronal Dysfunction; Pathology; Pattern; Performance; Phase; Positron-Emission Tomography; Process; Reporting; Research; Staging; Stream; System; Temporal Lobe; Visual; White Matter Disease; age effect; age related; amyloid pathology; beta amyloid pathology; design; directed attention; disease diagnosis; executive function; forgetting; male; memory encoding; neuroimaging; pre-clinical; public health relevance; relating to nervous system; research study; selective attention

DESCRIPTION (provided by applicant): Although episodic memory is traditionally associated with the medial temporal lobe system, it is clear that top-down processes subserved by frontoparietal regions interact with this system to influence what information is encoded. Top-down processes (ie. control processes) originate in "top" regions (ie. frontoparietal) and influence "bottom" sensorimotor regions to complete goal directed behavior. Given that successful encoding depends on directing attention to towards relevant information as well as inhibiting irrelevant information, it is not surprising that subsequent memory contrasts (activatio for subsequently remembered versus forgotten items) reveals FP activation. Although the relevance of top-down processes during episodic memory encoding can be inferred by examining activation related to subsequent memory effects, few studies have implemented a design that varies top-down processes during memory encoding. Furthermore, dysfunction in medial temporal lobe and FP networks is consistently reported in aging, and it is unclear how disruption within these networks influences memory performance in aging. Interestingly, a substantial proportion number of clinically normal elderly individuals have elevated levels of beta-amyloid (A?) plaques, a pathology strongly associated with Alzheimer's disease (AD). Research investigating the relevance of early A? deposition suggests this pathology may be an initiating event that leads to neuronal dysfunction and neurodegeneration, cognitive loss and eventually AD. Within this framework, clinically normal individuals with high levels of A? are thought to represent the earliest signs of Alzheimer's disease ("preclinical AD"), with a delay of approximately 10 years between initial pathological accumulation and the onset of clinical dementia. Thus, an understanding of this preclinical stage is of utmost importance to uncover mechanisms underlying A?-induced neuronal dysfunction before the widespread damage that is typical in AD has occurred. Although research examining preclinical AD has focused on episodic memory decline (since this domain is the first to show decline in AD), it is possible that this pathology has an impact on top-down processes mediated by frontoparietal regions. For instance, A? deposition is highly prevalent throughout frontoparietal regions and decline in executive function is known to occur in close proximity to AD diagnosis. Thus, the overall goal of this proposal is to incorporate components of top-down processes (ie. selective attention and task switching) in an episodic memory design to better understand effects of age and A? on patterns of activation in frontoparietal regions.

描述（由申请人提供）：虽然情节记忆传统上与内侧颞叶系统相关，但很明显，由额顶叶区域辅助的自上而下的过程与该系统相互作用，以影响编码的信息。自上而下的流程（即控制过程）起源于“顶部”区域（即，额顶叶）和影响“底部”感觉运动区域以完成目标导向行为。鉴于成功的编码取决于将注意力引向相关信息以及抑制无关信息，因此随后的记忆对比（随后记住的与遗忘的项目的激活）揭示FP激活并不奇怪。虽然情节记忆编码过程中自上而下的过程的相关性可以通过检查与随后的记忆效应相关的激活来推断，但很少有研究在记忆编码过程中实施了改变自上而下过程的设计。此外，内侧颞叶和FP网络的功能障碍在衰老过程中一直有报道，目前还不清楚这些网络的破坏如何影响衰老过程中的记忆表现。有趣的是，相当一部分临床正常的老年人β-淀粉样蛋白（A？）斑块，一种与阿尔茨海默病（AD）密切相关的病理学。研究调查早期A？沉积表明这种病理可能是导致神经元功能障碍和神经变性、认知丧失和最终AD的起始事件。在这个框架内，临床正常的人与高水平的A？被认为代表阿尔茨海默病（“临床前AD”）的最早迹象，在初始病理学积累和临床痴呆发作之间延迟约10年。因此，了解这一临床前阶段对于揭示A？在AD中典型的广泛损伤发生之前，诱导神经元功能障碍。尽管研究临床前AD的研究集中在情景记忆衰退上（因为这一领域是第一个显示AD衰退的领域），但有可能 这种病理学对由额顶叶区域介导的自上而下的过程具有影响。例如，A？沉积在整个额顶叶区域非常普遍，并且已知执行功能的下降在AD诊断的附近发生。因此，本提案的总体目标是纳入自上而下流程的组成部分（即：选择性注意和任务切换）的情景记忆设计，以更好地了解年龄和A？额顶叶区域的激活模式