Early Markers Of Alzheimer Disease

工作摘要：阿尔茨海默病(AD)是几种神经退行性疾病(痴呆症)中最常见的，主要发生在晚年，偶尔在60岁之前，但更常见的是70岁以后。这项研究调查了巴尔的摩老龄化纵向研究(BLSA)参与者的预期心理、神经和神经心理变化。对60岁及以上的参与者进行神经学和神经心理学检查，重复许多在年龄较小时对这些受试者进行的测试。疑似阿尔茨海默病的诊断遵循NINCDS-ADRDA标准。在对之前的小样本研究结果的后续研究中，该部门的调查人员检查了患病前的神经心理测试分数，以确定本顿视觉保持测试的长期缺陷是否预测了巴尔的摩老龄化纵向研究的参与者几十年后患上阿尔茨海默氏病？S病。在诊断AD前1~3年、3~5年、5~10年、10~15年，视觉记忆错误6次或以上与错误次数少于6次的阿尔茨海默病、S病的相对危险度分别为5.69、2.11、1.76和1.83(p&lt；0.05)。诊断前15年或更长时间的相对风险并不显著(p&gt；0.10)。视觉记忆错误的数量越多，15年后患AD的风险就越高。这些发现表明，视觉记忆能力差可能代表AD在确诊前几年的早期表现，并表明在确诊前预防性治疗的机会窗口增加的可能性。我们还调查了强调阿尔法广度的执行功能测量，以了解执行任务和非执行任务之间的关系。非痴呆症老年参与者(N=417)接受了全面的认知电池测试。对年龄和词汇量进行调整的部分相关性表明，Alpha Span、WAIS-R数字广度分测试和流利性任务之间存在关联。采用正交旋转的成分分析显示，4个成分的解决方案(86%的方差)与执行变量对所有负荷有贡献。我们用计算出的组件指数预测ASP性能进行了回归分析。在考虑了年龄(6%的变异量)后，反映短暂注意和心理操作的一个成分解释了Alpha Span的13%的变异量；其他成分解释了小比例的变异量，11%解释了言语语言能力，2%解释了持续注意/心理跟踪，1%解释了视觉-知觉空间组织和规划。研究结果强调了在理解执行功能时考虑认知的执行和非执行方面的重要性。

Summary of work: Alzheimer's disease (AD) is the most widespread among several neurological degenerative diseases (dementias) that occur principally at later ages, occasionally before 60, but more frequently after age 70. This study examines prospective psychological, neurological, and neuropsychological changes in participants from the Baltimore Longitudinal Study of Aging (BLSA). Neurological and neuropsychological examinations are administered to participants aged 60 and older, repeating many of the tests that were administered to these subjects at earlier ages. Diagnoses of probable Alzheimer's disease follow the NINCDS-ADRDA criteria. In a follow-up to previous findings on a small sample, Section investigators examined premorbid neuropsychological test scores in order to determine whether long term deficits in the Benton Visual Retention Test predicted the development of Alzheimer?s disease decades later in participants from the Baltimore Longitudinal Study of Aging. The relative risks for Alzheimer?s disease associated with making 6 or more visual memory errors versus less than 6 errors at 1 to 3, 3 to 5, 5 to 10, and 10 to 15 years before the diagnosis of AD were 5.69, 2.11, 1.76, and 1.83 respectively (p<0.05). The relative risk for 15 or more years before diagnosis was not significant (p>0.10). A greater number of visual memory errors are associated with an increased risk of AD up to 15 years later. These findings suggest that poor visual memory performance may represent an early expression of AD years before diagnosis and point to the possibility of an increased window of opportunity for preventive treatment before definitive diagnosis. We also investigated executive function measures emphasizing Alpha Span to understand relationships among executive and non-executive tasks. Non-demented elderly participants (N=417) received a comprehensive cognitive battery. Partial correlations adjusting for age and vocabulary revealed associations among Alpha Span, WAIS-R Digit Span subtests, and fluency tasks. Component analysis with orthogonal rotation revealed a 4 component solution (86% of the variance) with executive variables contributing to all loadings. We performed regression analyses with calculated component indices predicting ASp performance. After accounting for age (6% of the variance), a component reflecting brief attention and mental manipulation accounted for 13% of variance in Alpha Span; other components accounted for small proportions of variance, 11% for verbal language ability, 2% for sustained attention/mental tracking, and <1% for visuo-perceptual spatial organization and planning. Results emphasize the importance of considering executive and non-executive aspects of cognition in understanding executive functioning.