Mnemonic Processing Deficits in Older Adults at Risk for Alzheimer's Disease

有阿尔茨海默病风险的老年人的记忆处理缺陷

• 批准号: 8306673
• 负责人: PAUL E GILBERT
• 金额: $ 21.45万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306673
• 关键词: Age; Age-associated memory impairment; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Apolipoprotein E; Behavior Therapy; Behavioral; Beryllium; Caring; Cognitive; Development; Early Diagnosis; Elderly; Elements; Epigenetic Process; Episodic memory; Functional disorder; Future; Genes; Grant; Health Care Costs; Hippocampus (Brain); Impaired cognition; Impairment; Individual; Intervention; Investigation; Laboratories; Life; Measures; Mediation; Memory; Methodology; Neurodegenerative Disorders; Neuropsychological Tests; Onset of illness; Pathology; Pattern; Performance; Persons; Play; Process; Quality of life; Retrieval; Risk Factors; Role; Semantic memory; Space Perception; Staging; Structure; Task Performances; Temporal Lobe; Testing; Time; United States; Visuospatial; age related; base; cognitive change; cognitive function; cost; design; episodic memory impairment; frontal lobe; frontal lobe function; hippocampal subregions; improved; innovation; memory process; neuroimaging; normal aging; novel; pre-clinical; research study; skills; social; standardize measure; tool; young adult

DESCRIPTION (provided by applicant): The characterization of cognitive impairment in older adults, and particularly those at risk for Alzheimer's disease (AD) is critically important. The most widely identified risk factors for AD are increasing age and the presence of the apolipoprotein E epsilon 4 allele. In order to delay age of AD onset and improve quality of life, it is important to identify cognitive changes in older adults as early as possible. The detection of early indicators of AD could reduce the cost of AD care by as much $100 billion per year in the U.S. and interventions that delay AD onset by two years could result in nearly two million fewer cases in 50 years. Therefore, the primary aim of this proposal is to use an innovative, process-oriented approach to examine deficits in specific mnemonic processes in older adults at risk for AD. Impaired episodic memory is regarded as a hallmark deficit in older adults and may serve as an early indicator of AD. The accurate encoding and retrieval of one episodic memory from another may require the function of multiple mnemonic processes to associate the elements of an episodic memory together and also separate the elements from those belonging to a different memory to avoid catastrophic interference. Although episodic memory may involve various cortical regions, there is strong evidence that the hippocampus plays a critical role in supporting specific mnemonic processes such as pattern separation and the formation of arbitrary associations that may enhance episodic memory accuracy. Despite overwhelming evidence suggesting that hippocampal pathology is highly associated with aging, studies have not adequately examined these specific memory processes in older adults at risk for AD. The proposed experiments are highly significant because behavioral tasks that measure these specific mnemonic processes may be powerful and largely unexamined tools for the early detection of age-related cognitive dysfunction. Disruption of these processes may result in impairments in various cognitive functions critical to the execution of daily living skills. The identification of key mnemonic processing deficits may result in behavioral interventions that structure daily living tasks to mitigate interference and enhance memory. Five novel experiments will be used in the proposed studies to provide a highly innovative investigation of specific memory processes in young adults and older adults at risk for AD. The aims of the grant will characterize age-related differences on the proposed experiments (Specific Aim 1), examine relationships between performance on the experiments and standardized neuropsychological tests (Specific Aim 2), and characterize the performance of older adults, with and without the APOE E4 allele on the experiments (Specific Aim 3). If the innovative aims of the present grant are achieved, novel behavioral approaches and methodologies will be developed for future aging studies investigating: 1) episodic memory impairment, 2) hippocampal subregion specific epigenetic and transcriptional changes, 3) structural and functional hippocampal changes using neuroimaging, and 4) the differentiation of preclinical markers of AD from those of normal aging.

描述（由申请人提供）：老年人的认知障碍的表征，尤其是那些患阿尔茨海默氏病风险的人（AD）至关重要。广泛确定的AD风险因素是增加年龄和载脂蛋白E Epsilon 4等位基因。为了延迟AD发作的年龄并改善生活质量，重要的是要尽早确定老年人的认知变化。在美国，对AD的早期指标的检测可能每年减少1000亿美元，并将AD发作的干预措施降低两年，可能会导致50年内少近200万个病例。因此，该提案的主要目的是使用一种创新的，以过程为导向的方法来检查具有AD风险的老年人的特定助记符过程中的缺陷。情节记忆受损被认为是老年人的标志性赤字，可以作为AD的早期指标。从另一个情节记忆中的一个情节记忆的准确编码和检索可能需要多个助记符过程的函数，以将情节内存的元素联系在一起，并将元素与属于不同存储器的元素分开，以避免灾难性干扰。尽管情节记忆可能涉及各种皮质区域，但有力的证据表明，海马在支持特定的助记符过程中起着至关重要的作用，例如模式分离和形成了可能提高情节记忆精度的任意关联。尽管有很多证据表明海马病理学与衰老高度相关，但研究尚未充分检查处于AD风险的老年人中的这些特定记忆过程。提出的实验非常重要，因为测量这些特定助记符过程的行为任务可能是强大的，并且在很大程度上未经审查的工具可以早期检测与年龄相关的认知功能障碍。这些过程的破坏可能会导致各种认知功能受损，这对于日常生活技能的执行至关重要。关键助记符处理缺陷的识别可能会导致行为干预措施，以减轻干扰和增强记忆力。拟议的研究将使用五个新型实验，以对年轻人和有AD风险的年轻人和老年人的特定记忆过程进行高度创新的研究。赠款的目的将表征与年龄相关的实验差异（特定目标1），检查实验的性能与标准化的神经心理学测试之间的关系（特定的目标2），并表征老年人的性能，以及在实验上没有APOE E4等位基因（具体目标3）。如果实现了当前赠款的创新目标，将开发出新的行为方法和方法论，以进行未来的衰老研究研究：1）情节记忆障碍，2）海马次区域特异性表观遗传和转录变化，3）结构和功能性的海上水平变化，使用神经模仿，以及4）从这些良好的标记范围差异来划分。