Mechanisms of Executive Decline in Normal Aging

描述（由申请人提供）：母体RO 1的总体目标是确定衰老过程中观察到的执行功能下降的认知机制和神经结构。我们的工作模型是，年龄相关的额叶萎缩，额叶灌注不足，以及白色物质完整性的损失相互作用，影响信息处理速度和执行功能。父母RO 1前瞻性研究180名正常老年人的结构神经成像，灌注和认知测量在基线和30-36个月后再次。这项竞争性修订的具体目的是在随访评估时增加空腹抽血，以获得炎症和血管风险的定量实验室指标。虽然父RO 1旨在评估年龄和生活方式对大脑结构和认知的影响，但没有程序来收集潜在介导这些关系的生物机制的关键数据。越来越清楚的是，炎症和血管风险是认知老化的重要因素，即使没有神经退行性疾病。更清楚地描述炎症和血管风险的实验室测量如何与大脑结构和认知相互作用，将大大提高我们对年龄相关认知变化机制的理解，并将直接导致有针对性的干预措施。 公共卫生相关性：本竞争修订版建议在随访评估时增加空腹抽血，以获得180名功能正常老年人队列的炎症和血管风险的定量实验室指标。这些额外的生物学信息，当与父母RO 1的生活方式和健康变量，神经影像学数据和认知测量相结合时，将使我们能够解决与年龄相关的认知变化机制相关的具体问题。

DESCRIPTION (provided by applicant): The overarching goal of the parent RO1 is to identify the cognitive mechanisms and neural structures that underlie the decline in executive functioning observed in aging. Our working model is that age-associated frontal atrophy, frontal hypoperfusion, and loss of white matter integrity interact to affect information processing speed and executive function. The parent RO1 is prospectively studying 180 normal elderly with structural neuroimaging, perfusion, and cognitive measures at baseline and again after 30-36 months. The specific aim of this competing revision is to add a fasting blood draw at the follow-up assessments to obtain quantitative laboratory measures of inflammation and vascular risk. While the parent RO1 is designed to assess the impact of age and lifestyle on brain structure and cognition, there are no procedures to collect key data on biological mechanisms that potentially mediate these relationships. It is increasingly clear that inflammation and vascular risk are highly important factors in cognitive aging, even in the absence of neurodegenerative disease. A clearer delineation of how laboratory measures of inflammation and vascular risk interact with brain structure and cognition will significantly advance our understanding of the mechanisms underlying age-related cognitive change and will directly lead to targeted interventions. PUBLIC HEALTH RELEVANCE: This Competing Revision proposes to add a fasting blood draw at the follow-up assessments to obtain quantitative laboratory measures of inflammation and vascular risk on a cohort of 180 functionally normal elderly. This additional biological information, when combined with the parent RO1's lifestyle and health variables, neuroimaging data, and cognitive measures, will enable us to address specific questions about the mechanisms underlying age-related cognitive change.