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）：老年人认知障碍的特征，特别是那些有阿尔茨海默病（AD）风险的老年人，是至关重要的。最广泛确定的 AD 危险因素是年龄增长和载脂蛋白 E epsilon 4 等位基因的存在。为了延缓 AD 发病年龄并提高生活质量，尽早识别老年人的认知变化非常重要。在美国，检测 AD 早期指标可以使 AD 护理成本每年减少 1000 亿美元，而将 AD 发病延迟两年的干预措施可能会在 50 年内减少近 200 万例病例。因此，该提案的主要目的是使用一种创新的、面向过程的方法来检查有 AD 风险的老年人的特定记忆过程中的缺陷。情景记忆受损被认为是老年人的标志性缺陷，并且可能作为 AD 的早期指标。对一个情景记忆的准确编码和从另一个情景记忆的检索可能需要多个助记过程的功能，以将情景记忆的元素关联在一起，并将这些元素与属于不同记忆的元素分开，以避免灾难性干扰。尽管情景记忆可能涉及各个皮质区域，但有强有力的证据表明，海马体在支持特定记忆过程（例如模式分离和任意关联的形成）方面发挥着关键作用，这些过程可能会提高情景记忆的准确性。尽管大量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有 AD 风险的老年人的这些特定记忆过程。所提出的实验非常重要，因为测量这些特定记忆过程的行为任务可能是早期检测与年龄相关的认知功能障碍的强大且很大程度上未经检验的工具。这些过程的中断可能会导致对执行日常生活技能至关重要的各种认知功能受损。识别关键的记忆处理缺陷可能会导致行为干预，从而构建日常生活任务以减轻干扰并增强记忆。拟议的研究将使用五项新颖的实验，对有 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。该赠款的目的将描述拟议实验中与年龄相关的差异（具体目标 1），检查实验表现与标准化神经心理学测试之间的关系（具体目标 2），并描述老年人的表现，无论是否有实验中的 APOE E4 等位基因（具体目标 3）。如果实现本资助的创新目标，将为未来的衰老研究开发新的行为方法和方法，调查：1）情景记忆障碍，2）海马亚区域特定的表观遗传和转录变化，3）使用神经影像学的结构和功能海马变化和 4) AD 临床前标志物与正常衰老标志物的区别。