Age, Physical Activity, Genotype and Cognitive Function

描述(由申请人提供)：本研究的目的是探讨老年男性和女性(50-65岁)的体力活动史和脑过程之间的关系，特别是那些具有晚发性阿尔茨海默病遗传风险的人(即，APOE e4等位基因携带者)。神经成像研究显示，认知正常的中年e4携带者在脑海马和前额叶皮质进行精神挑战时，大脑代谢相对低下，这表明参与AD的同一大脑区域的代谢异常。最近的流行病学研究表明，与久坐不动的e4携带者相比，体力活动较多的老年e4携带者在认知能力下降方面表现出显著的缓解。此外，最近的动物研究表明，自愿运动对海马区的神经营养作用。总而言之，这些研究表明，体力活动对老化的大脑有改善的影响，并可能减缓早期AD的进展。因此，根据体力活动水平(高v低)和基因型(e4等位基因存在v缺失)分为四组的52名参与者将接受磁源成像(MEG)，以评估认知挑战期间的海马区和前额叶活动。我们预测，中年男性和女性的体力活动状况将与海马区活动较高、前额叶区域活动较低有关。此外，在e4等位基因的活跃携带者和低活跃携带者之间，这些差异的幅度将最大。检测到中年成年人大脑活动的这种相关差异将表明，体育活动对年龄相关的神经退化具有改善影响，并对AD进展起到保护作用。

DESCRIPTION (provided by applicant): The purpose of the present study is to address the relationship between physical activity history and brain processes in older men and women (50 - 65 years), particularly in those who are genetically at risk for late-onset Alzheimer's Disease (i.e., carriers of the APOE e4 allele. Neuroimaging studies reveal relative hypoactivation of brain metabolism in cognitively normal middle-aged e4 carriers during mental challenge in hippocampus and prefrontal cortex, indicative of metabolic abnormality in the same brain regions that are involved in AD. Recent epidemiological study indicates that physically active older e4 carriers show remarkable attenuation in cognitive decline relative to sedentary carriers of e4. In addition, recent animal research indicates neurotrophic effects of voluntary exercise on the hippocampal region. Collectively, these studies suggest an ameliorative influence of physical activity on the aging brain and a potential slowing of early-stage AD progression. Accordingly, 52 participants classified by physical activity level (high v low) and genotype (e4 allele present v absent) to form four groups will undergo magnetic source imaging (MEG) to assess hippocampal and prefrontal activity during cognitive challenge. We predict that physical activity status in middle-aged men and women will be associated with higher activity in hippocampus and lower activity in prefrontal region. Furthermore, the magnitude of these differences will be greatest between active and low-active carriers of the e4 allele. Detection of such related differences in brain activity in middle-aged adults would suggest an ameliorative influence of physical activity on age-related neurodegeneration and a protective role for AD progression.