BEHAVIORAL STUDIES OF COGNITIVE FUNCTION

认知功能的行为研究

• 批准号: 7613347
• 负责人: Mark Barry Moss
• 金额: $ 40.23万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7613347
• 关键词: Accounting; Address; Affect; Age; Age-Years; Age-associated memory impairment; Aging; Alzheimer' s Disease; Amyloid; Amyloid deposition; Animals; Anisotropy; Area; Astrocytes; Attention; Behavioral; Belief; Biochemical; Brain; Brain region; Butter; Cells; Cerebral cortex; Chromosome Pairing; Cognition; Cognitive; Computer information processing; Corpus Callosum; Critical Pathways; Cross-Sectional Studies; Data; Dementia; Dependence; Development; Diffusion; Discrimination Learning; Disruption; Educational workshop; Efferent Pathways; Elderly; Event; Fire - disasters; Functional disorder; Future; Gene Expression; Gene Proteins; Genes; Goals; Gray unit of radiation dose; Hippocampal Formation; Human; Image; Immunity; Impaired cognition; Impairment; Individual; Inflammation; Inflammatory; Intervention Studies; Knowledge; Laws; Learning; Limbic System; Link; Literature; Longitudinal Studies; Macaca mulatta; Magnetic Resonance Imaging; Measures; Medial; Mediator of activation protein; Memory; Microglia; Modeling; Monkeys; Morphology; Mosses; Myelin; N(delta)-acetylornithine, -isomer; N-dodecanoylglutamic acid, -isomer, sodium salt; Names; Natural History; Nature; Neurobiology; Neurons; Neurotransmitters; Outcome; Outcome Measure; Oxidative Stress; Parahippocampal Gyrus; Pathway interactions; Pattern; Performance; Physiological; Physiology; Play; Population; Prefrontal Cortex; Primates; Process; Prosencephalon; Proteins; Pyramidal Cells; Range; Rate; Research; Retrograde Memory Losses; Role; Score; Senile Plaques; Short-Term Memory; Signal Transduction; Staging; Structure; Synapses; System; Temporal Lobe; Testing; Thinking; Time; Transcriptional Activation; Up-Regulation; Vision; Visual; Work; age related; aged; aging brain; alpha-difluoromethyl-DOPA, -isomer; alpha-methylornithine dihydrochloride, -isomer; awake; base; behavior test; classical conditioning; cognitive change; cognitive function; cohort; design; early onset; executive function; expectation; functional outcomes; in vivo; indexing; insight; interest; memory recognition; middle age; mild neurocognitive impairment; neural circuit; neuroimaging; neuron loss; neuronal circuitry; neuropsychological; nonhuman primate; normal aging; programs; white matter; white matter change; young adult

Normal human aging is typically characterized by a mild decline in cognition, particularly for memory and executive system function. Of interest, some individuals evidence virtually no change in cognition with age. Others evidence a marked decline, but not to the level of Alzheimer's disease or other dementia state. To date, the neurobiological basis of so called "successful" vs. "unsuccessful" aging remains unclear. The cumulative findings from this program have moved us closer to the belief that the degradation of forebrain white matter may play the key role in the cognitive decline of normal aging. Accordingly, Project 1 will continue to serve two roles: In the first, we will continue using a comprehensive set of tasks to assess cognition in our cohort of 42 monkeys (12 young, 18 middle aged and 12 old) using a cross-sectional design. This will allow us to help identify not only the emergence of the initial impairment in cognition, but in consort with the other 3 projects, to narrow our search for the neurobiological alterations that underlie these cognitive changes. In our second role, we will conduct, for the first time we believe, a behavioral longitudinal study in the aged rhesus monkey. Early middle age monkeys (N=12) will be tested at six time points over a period of 4.5 yrs when they reach at age of 18-20 years (a time frame roughly equivalent to 14 human years) This range covers a point when monkeys evidence no impairment to a point when 2/3 show either mild or marked impairment. This will allow us to track the natural history of cognitive decline and permit the unique opportunity to assess retrograde memory loss and its relationship to anterograde memory and new learning, an important but difficult variable to assess in human aging research. Volumetric MRI, DTI, CSF, and other measures will be conducted in parallel to identify in vivo, possible neurobiologic correlates of decline. The proposed longitudinal study is also an important first step for possible future intervention studies that will target pathogenic proteins and genes now being identified in the aging brain.

正常的人类衰老的典型特征是认知，特别是记忆力的轻度下降， 执行系统功能有趣的是，有些人的认知几乎没有随着年龄的变化。 其他证据表明有明显下降，但没有达到阿尔茨海默病或其他痴呆状态的水平。到 迄今为止，所谓的“成功”与“不成功”衰老的神经生物学基础仍不清楚。的 这个项目的累积发现使我们更接近于相信， 白色物质可能在正常衰老的认知能力下降中起关键作用。因此，项目1将 继续发挥两个作用：第一，我们将继续使用一套全面的任务来评估 在我们的42只猴子（12只年轻，18只中年和12只老年）的队列中，使用横断面 设计这将使我们不仅能够帮助识别认知最初障碍的出现， 与其他3个项目合作，缩小我们对这些神经生物学改变的搜索范围。 认知变化在我们的第二个角色中，我们将首次进行我们认为是行为上的 对老年恒河猴的纵向研究。将在6个时间点对中年早期猴（N=12）进行检测 当他们达到18-20岁时，在4.5年的时间内（大约相当于14岁）， 这个范围涵盖了猴子没有表现出损伤的点，到2/3的猴子表现出损伤的点。 轻微或明显的损伤。这将使我们能够跟踪认知能力下降的自然历史， 允许独特的机会来评估逆行性记忆丧失及其与顺行性记忆的关系 和新的学习，这是人类衰老研究中一个重要但难以评估的变量。容积MRI， 将同时进行DTI、CSF和其他测量，以确定体内可能的神经生物学 下降的相关性。拟议的纵向研究也是今后可能开展的重要的第一步。 干预性研究，将针对致病蛋白质和基因，现在正在确定在老化的大脑。