High-resolution imaging of hippocampal mechanisms in age-related memory decline.

与年龄相关的记忆衰退的海马机制的高分辨率成像。

• 批准号: 8925763
• 负责人: Anthony D Wagner
• 金额: $ 36.29万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8925763
• 关键词: Accounting; Address; Adult; Affect; Age; Aging; Alzheimer' s Disease; Apical; Area; Atrophic; Attenuated; Behavior; Biological Assay; Biological Markers; Brain; Brain imaging; Cereals; Cerebrospinal Fluid; Data; Dementia; Deterioration; Development; Diagnostic; Disease; Elderly; Episodic memory; Event; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Health; High Prevalence; Hippocampus (Brain); Human; Image; Imaging Techniques; Imaging technology; Intervention; Learning; Literature; Magnetic Resonance Imaging; Measures; Mediating; Memory; Memory Loss; Methods; Modeling; Multivariate Analysis; Nature; Neurophysiology - biologic function; Neuropil; Participant; Pathology; Patients; Pattern; Performance; Persons; Population; Research; Resolution; Retrieval; Structure; Symptoms; Testing; Width; Work; age related; base; daily functioning; dentate gyrus; healthy aging; imaging biomarker; in vivo; indexing; innovation; memory recognition; mild cognitive impairment; pre-clinical; stem; tau Proteins

DESCRIPTION (provided by applicant): Memory decline is a frequent symptom among aging adults. A substantial literature points to an age-related deterioration of episodic memory (the capacity to encode and subsequently retrieve memories for events). The hippocampus is critical for episodic memory, and comprises multiple subfields thought to contribute differentially to pattern separation and pattern completion - fundamental mechanisms of memory -- and to exhibit differential vulnerability to age. In particular, selective changes in hippocampal subfield structure and function may drive age-related changes in memory performance, and these changes may relate, in part, to preclinical evidence of Alzheimer's disease (AD) pathology. Recent developments in high-resolution magnetic resonance imaging (MRI), including (a) high-resolution functional MRI (hr-fMRI) combined with powerful multivariate analysis methods and (b) ultra-high field 7T structural MRI, provide a means to study human hippocampal subfields in vivo and to examine hippocampal mechanisms of memory. Here, we propose to apply these innovative MRI techniques to a large, 200-person cross-sectional population of healthy older adults (e60 years) to test the following central hypothesis: In older adults, selective changes in hippocampal subfield function and structure drive mechanistic changes in pattern separation and pattern completion, which relate to age-related decline in associative recollection (a central form of episodic memory) and, in part, to preclinical AD pathology. In Aim 1, we will use hr-fMRI at 3T, along with representational similarity analysis and multivoxel pattern analysis, to quantitatively estimate hippocampal pattern separation at encoding and pattern completion at retrieval, with the latter indexed by cortical reinstatement; we further aim to relate these quantitative measures of hippocampal function to associative recollection and item recognition memory performance. In Aim 2, we will use high-resolution structural MRI at 7T to quantify hippocampal subfield structural atrophy, and we will relate these structural measures to our quantitative hr-fMRI indices of pattern separation and cortical reinstatement, as well as to memory behavior. In Aim 3, we will relate cerebrospinal fluid assays of AD biomarkers (Abeta42, tau, and phospho-tau proteins) to hr- fMRI functional metrics, 7T MRI hippocampal subfield structural metrics, and memory behavior. The novelty and power of the proposed research, which is grounded in strong preliminary data, derives from our ability to synthesize data across these Aims to discover how function, structure, and early pathology interact to affect episodic memory in aging. The project may ultimately inform diagnostic and intervention approaches for addressing age-related memory decline in unimpaired older adults, as well as those suffering from amnestic Mild Cognitive Impairment and AD.

描述（由申请人提供）：记忆下降是衰老的成年人的常见症状。大量文献指出了与年龄相关的情节记忆恶化（编码和随后检索事件的记忆的能力）。海马对于情节记忆至关重要，并且包括多个子场，被认为对模式分离和模式完成 - 记忆的基本机制有所不同，并表现出与年龄的不同脆弱性。特别是，海马子场的选择性变化 结构和功能可能会导致与年龄相关的记忆性能变化，这些变化可能部分与阿尔茨海默氏病（AD）病理学的临床前证据有关。高分辨率磁共振成像（MRI）的最新发展，包括（a）高分辨率功能性MRI（HR-FMRI）与强大的多元分析方法以及（b）超高场7T结构MRI相结合，提供了一种研究人类海马子领域的手段，以检查人类的河马子场，并检查了海马机械的记忆力。 Here, we propose to apply these innovative MRI techniques to a large, 200-person cross-sectional population of healthy older adults (e60 years) to test the following central hypothesis: In older adults, selective changes in hippocampal subfield function and structure drive mechanistic changes in pattern separation and pattern completion, which relate to age-related decline in associative recollection (a central form of episodic memory) and, in part, to preclinical AD病理。在AIM 1中，我们将在3T处使用HR-FMRI，以及代表性的相似性分析和多毒素模式分析，以定量估计在检索时编码和模式完成时的海马模式分离，而后者则由皮质恢复索引；我们进一步旨在将这些对海马功能的定量度量与关联回忆和项目识别记忆表现相关联。在AIM 2中，我们将使用7T处的高分辨率结构MRI来量化海马子场结构萎缩，我们将将这些结构测量与我们的定量HR-FMRI指数相关联，该指数的模式分离和皮质恢复，以及记忆行为。在AIM 3中，我们将将AD生物标志物（ABETA42，TAU和磷酸-TAU蛋白）的脑脊液测定与HR-fMRI功能指标，7T MRI海马体子场结构指标和记忆行为相关联。拟议研究的新颖性和力量以强烈的初步数据为基础，源于我们能够在这些旨在综合数据的能力，以发现功能，结构和早期病理如何相互作用以影响衰老中的情节记忆。该项目最终可能会为诊断和干预方法提供信息，以解决未受损害的老年人以及患有柔和的轻度认知障碍和AD的年龄相关记忆的下降。