BEHAVIORAL STUDIES OF COGNITIVE FUNCTION

人类正常衰老的典型特征是认知能力轻度下降，特别是记忆力和 执行系统功能。有趣的是，一些人的认知能力几乎没有随着年龄的增长而改变。 其他证据表明，这一比例明显下降，但没有达到阿尔茨海默病或其他痴呆症的水平。至 到目前为止，所谓的“成功”和“不成功”衰老的神经生物学基础仍不清楚。这个 这个项目的累积发现让我们更接近这样一种信念，即前脑的退化 白质可能在正常衰老的认知衰退中起关键作用。因此，项目1将 继续担任两个角色：第一，我们将继续使用一套全面的任务来评估 我们对42只猴子(12只幼猴，18只中年猴和12只中年猴)的认知能力进行了横断面研究 设计。这将使我们不仅能够帮助识别最初认知障碍的出现，而且还有助于识别 与其他3个项目合作，以缩小我们对这些基础上的神经生物学变化的搜索范围 认知变化。在我们的第二个角色中，我们将第一次进行我们认为的行为 老年恒河猴的纵向研究。中年早期猴子(N=12)将进行六次测试 当他们在18-20岁(大致相当于14岁)时，在4.5年内获得积分 人类年)这一范围涵盖了猴子没有证据的损害到2/3出现的点 轻微的或明显的损害。这将使我们能够追踪认知衰退的自然历史 提供独特的机会评估逆行性记忆丧失及其与顺行性记忆的关系 以及新的学习，这是人类老龄化研究中一个重要但难以评估的变量。体积磁共振成像， DTI、CSF和其他措施将并行进行，以在体内确定可能的神经生物学 衰退的关联性。拟议的纵向研究也是可能的未来的重要的第一步 干预研究将针对目前正在老化的大脑中识别的致病蛋白和基因。

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.