Age, Physical Activity, Genotype and Cognitive Function

描述（由申请人提供）：本研究的目的是解决老年男性和女性（50 - 65岁）身体活动史和大脑过程之间的关系，特别是在那些遗传上有迟发性阿尔茨海默病风险的人中（即，APOE e4等位基因携带者。神经影像学研究显示，认知正常的中年e4携带者在海马和前额叶皮层的精神挑战期间，大脑代谢相对活化不足，表明与AD相关的相同大脑区域的代谢异常。最近的流行病学研究表明，相对于久坐的e4携带者，身体活跃的老年e4携带者在认知能力下降方面表现出显着的减弱。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。总的来说，这些研究表明身体活动对衰老大脑的改善影响和早期AD进展的潜在减缓。因此，52名参与者按身体活动水平（高v低）和基因型（e4等位基因存在v不存在）分类形成四组，将接受磁源成像（MEG），以评估认知挑战期间的海马和前额活动。我们预测，中年男性和女性的体力活动状况将与海马体的较高活动和前额区的较低活动相关。此外，这些差异的幅度将在e4等位基因的活跃和低活跃携带者之间最大。在中年人的大脑活动中检测到这种相关的差异将表明身体活动对年龄相关的神经退行性变的改善作用和对AD进展的保护作用。

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.