Early Markers Of Alzheimer Disease

阿尔茨海默病的早期标志

• 批准号: 6535840
• 负责人: Alan B Zonderman
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6535840
• 关键词: Alzheimer's disease; aging; brain disorder diagnosis; clinical research; cognition disorders; dementia; diagnosis design /evaluation; human middle age (35-64); human old age (65+); human subject; longitudinal human study; nervous system disorder epidemiology; neuropsychological tests

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.

工作总结：阿尔茨海默病（AD）是主要发生在较晚年龄的几种神经退行性疾病（痴呆）中最普遍的，偶尔在60岁之前，但更频繁地在70岁之后。本研究探讨了前瞻性的心理，神经和神经心理学的变化，参与者从巴尔的摩纵向研究老化（BLSA）。对60岁及以上的参与者进行神经学和神经心理学检查，重复在早期对这些受试者进行的许多测试。可能的阿尔茨海默病的诊断遵循NINCDS-ADRDA标准。在一个小样本的后续行动，以前的研究结果，部分调查人员检查了发病前的神经心理测试分数，以确定是否长期赤字本顿视觉保留测试预测阿尔茨海默病的发展？几十年后，来自巴尔的摩老龄化纵向研究的参与者患上了老年痴呆症。老年痴呆症的相对风险？在AD诊断前1 ~ 3年、3 ~ 5年、5 ~ 10年和10 ~ 15年，出现6个或6个以上视觉记忆错误的AD患者与出现少于6个视觉记忆错误的AD患者相比，差异分别为5.69、2.11、1.76和1.83（p<0.05）。诊断前15年或更长时间的相对危险度无显著性差异（p>0.10）。更多的视觉记忆错误与15年后AD风险增加有关。这些研究结果表明，视觉记忆表现不佳可能代表AD在诊断前数年的早期表达，并指出在确诊前预防性治疗的机会窗口增加的可能性。 我们还研究了执行功能的措施，强调阿尔法跨度，以了解执行和非执行任务之间的关系。非痴呆老年参与者（N=417）接受了全面的认知电池。偏相关调整的年龄和词汇量之间的关联揭示了阿尔法跨度，WAIS-R数字跨度子测试，流畅性任务。正交旋转的成分分析揭示了4个成分的解决方案（86%的方差）与执行变量有助于所有负载。我们进行了回归分析与计算的组件指数预测ASp的性能。在考虑年龄因素（6%的方差）后，反映短暂注意力和心理操作的成分占阿尔法跨度方差的13%;其他成分占较小比例的方差，口头语言能力占11%，持续注意力/心理跟踪占2%，视觉感知空间组织和规划<1%。结果强调，考虑执行和非执行方面的认知理解执行功能的重要性。