Early Markers Of Alzheimer Disease

阿尔茨海默病（AD）是几种神经退行性疾病（痴呆症）中最普遍的，主要发生在老年，偶尔发生在60岁之前，但更常见的是在70岁之后。本研究考察了巴尔的摩老龄化纵向研究（BLSA）参与者的前瞻性心理、神经学和神经心理学变化。对60岁及以上的参与者进行神经学和神经心理学检查，重复对这些受试者在早期进行的许多测试。诊断可能的阿尔茨海默病遵循NINCDS-ADRDA标准。在一个小样本的后续研究中，研究人员检查了发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示着阿尔茨海默病的发展？几十年后，巴尔的摩老龄化纵向研究的参与者发现了这种疾病。患老年痴呆症的相对风险是什么？在AD诊断前1 ~ 3年、3 ~ 5年、5 ~ 10年和10 ~ 15年发生6次或以上视觉记忆错误与小于6次错误相关的疾病分别为5.69、2.11、1.76和1.83 （p<0.05）。诊断前15年及以上的相对风险无显著性差异（p < 0.05）。大量的视觉记忆错误与15年后患阿尔茨海默病的风险增加有关。这些研究结果表明，较差的视觉记忆表现可能代表AD在诊断前几年的早期表现，并指出在明确诊断前进行预防性治疗的机会增加的可能性。我们还研究了执行功能测量，强调Alpha跨度来理解执行任务和非执行任务之间的关系。无痴呆的老年参与者（N=417）接受了全面的认知测试。调整年龄和词汇量的部分相关性揭示了α广度、WAIS-R数字广度子测试和流利性任务之间的关联。用正交旋转进行的成分分析揭示了一个4成分的解决方案（86%的方差），其中执行变量对所有负载都有贡献。我们用计算出的预测ASp性能的成分指数进行了回归分析。在考虑了年龄（6%的方差）后，反映短暂注意力和心理操纵的成分占Alpha Span方差的13%；其他成分占方差的比例较小，语言能力占11%，持续注意/心理跟踪占2%，视觉感知空间组织和规划占<1%。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.