Effects of Aging on Episodic Memory Encoding: Neuroimaging Studies

描述（由申请人提供）：虽然痴呆症和中风只影响一小部分人口，但如果我们活得足够长，有一种大脑功能障碍会影响我们所有人：正常衰老。随着年龄的增长，我们大脑的解剖和功能完整性会下降，我们的认知能力也会下降。即使相对温和，这种下降也影响到许多人，因此对人口一级的影响很大。任何合理的治疗方法的发展都取决于对健康老龄化对认知神经基础的影响的清晰理解。此外，这些知识对于研究阿尔茨海默病的破坏性影响至关重要。拟议的研究将通过直接将认知能力中与年龄相关的缺陷与大脑解剖和功能中与年龄相关的缺陷联系起来来促进这一知识。该方法集成了过去很少结合的3种方法。首先，我们将使用功能性磁共振成像（fMRI）来研究随着年龄增长而变化的大脑活动。我们希望发现，在老化的大脑中，活动信号缺陷认知处理的减少与年龄无关，但活动信号补偿机制的增加与年龄相关。其次，我们将使用弥散张量成像（DTI）来测量衰老对白质完整性的影响，因为有证据表明，衰老不仅会损害单个大脑区域，还会损害它们之间的连接。最后，我们将使用一套全面的标准化测试来确定老年人群中神经心理状态的个体差异。受健康（和病理性）衰老影响最大的认知功能之一是情景记忆，它是指对个人经历的过去事件的记忆。我们提出了六个功能磁共振成像研究，以调查与获取情节信息（编码）的大脑活动的老化的影响。大脑中有两个区域对编码特别重要：前额叶皮层和内侧颞叶。我们将测量这些区域的活动及其相互作用，同时年轻和老年参与者在扫描仪中学习新的情节信息。特别是，我们将调查两个关键因素占年龄相关的缺陷编码（1）减少认知资源。为了研究这个因素，我们将在编码过程中分配注意力并改变刺激呈现的速度。(2)绑定过程受损。为了研究这个因素，我们将比较项目的记忆与语义或感知关联的记忆。最后，我们将研究这两个因素之间的相互作用。公共卫生相关性：这些研究结果将有助于阐明年龄相关的情景编码缺陷的神经相关性，并对促进健康具有重要意义。它们将有助于开发认知训练方法，并将为阿尔茨海默病的研究提供重要的基线。

DESCRIPTION (provided by applicant): Whereas dementia and stroke affect only fraction of the population, there is a type of brain dysfunction that will affect all of us if we live long enough: normal aging. As we age, the anatomical and functional integrity of our brain declines, and so do our cognitive abilities. Even if relatively mild, this decline affects a large number of people, and hence, it has a great impact at the population level. The development of any rational remedial approach depends on a clear understanding of the effects of healthy aging on the neural basis of cognition. Moreover, this knowledge is critical for research on the devastating effects of Alzheimer's Disease. The proposed research will contribute to this knowledge by directly linking age-related deficits in cognitive abilities to age-related deficits in brain anatomy and function. The approach integrates 3 methodological approaches that have been seldom combined in the past. First, we will use functional MRI (fMRI) to brain activity that changes as a function of aging. We expect to find not age-related decreases in activity signaling deficit cognitive processing, but also age-related increases in activity signaling compensatory mechanisms in the aging brain. Second, we will use diffusion tensor imaging (DTI) to measure the effects of aging on white-matter integrity, as there is evidence that aging impairs not only individual brain regions but also the connections between them. Finally, we will use a comprehensive batter of standardized tests to identify individual differences in neuropsychological status within the aging population. One of the cognitive functions most affected by healthy (and pathological) aging is episodic memory, which refers to memory for personally experienced past events. We propose six fMRI studies to investigate the effects of aging on brain activity associated with acquiring episodic information (encoding). Two brain regions are particularly important for encoding: the prefrontal cortex and the medial temporal lobes. We will measure activity in these regions, and their interactions, while young and older participants learn new episodic information in the scanner. In particular, we will investigate two critical factors accounting for age-related deficits in encoding (1) Reduced cognitive resources. To investigate this factor, we will divide attention and vary the speed of stimuli presentation during encoding. (2) Impaired binding processes. To investigate this factor we will compare memory for items vs. memory for semantic or perceptual associations. Finally, we will investigate the interactions between these two factors. PUBLIC HEALTH RELEVANCE: The results of the proposed studies will clarify the neural correlates of age-related deficits in episodic encoding, and will have important implications for the promotion of health. They will help develop cognitive training methods and will provide an essential baseline for research on Alzheimer's Disease.