Early Markers Of Alzheimer Disease

阿尔茨海默病的早期标志

• 批准号: 6674100
• 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/6674100
• 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. To characterize the relationship between age-related memory change and repeat testing, we investigated longitudinal change and the effects of age, sex, education, and repeat testing on new learning and recall by analyzing measures of verbal learning and interference, short and long-delay free and cued recall and recognition hits in separate mixed-effects regressions. We found cross-sectional effects of age (p<0.001) and sex (p<0.05) on learning and interference, regardless of baseline performance. Younger adults outperformed older adults, and women outperformed men. There were longitudinal age changes across total learning, long-delay free and cued recall regardless of baseline scores (p<0.05). In addition, controlling for baseline scores enhanced the sensitivity for detection of longitudinal age changes on short-delay cued recall and recognition hits (p<0.05). The influence of repeated administrations changed with advancing baseline age for total learning and short and long-delay recall such that younger baseline age was associated with improvement over time while older baseline age was associated with decline over time. There are declines in verbal learning performance associated with normal aging that are influenced by baseline age. Failing to account for the influence of repeat testing with aging may decrease sensitivity to detect pathological decline. Section investigators developed a computerized method to help predict individuals at risk for developing Alzheimer's disease based on longitudinal changes in memory as tool for clinicians in managing treatment plans for potential dementia AD patients. Using the initial level and rates of change in visual memory performance, we performed longitudinal case-control study of 52 women and 145 men using pre-morbid tests of visual memory and neurological examinations to identify individuals with and without dementia and AD. The classification method for each individual starts on the second examination and proceeds to compute that person's risk of AD one examination at a time based on all the follow-up information of the remaining individuals. By performing a cross-validation study and using the optimal combination of sensitivity and specificity derived from a receiver operating characteristic (ROC) curve, 65% of the Alzheimer cases and 75% of the non-cases were correctly classified for females, while 65% and 60% of cases and non-cases, respectively, were correctly classified for males. Section investigators used virtual environment (VE) technology to assess spatial navigation in humans to quantify age-related deficits in human spatial navigation and to promote a comparative approach to the neuroscience of cognitive aging. We assessed age differences in navigational behavior in a VE and examined the relationship between this navigational measure and other more traditional measures of cognitive aging. Following pre-training, participants were confronted with a VE spatial learning task and completed a battery of cognitive tests. The VE consisted of a richly textured series of interconnected hallways, some leading to dead ends and others leading to a designated goal location in the environment. Compared to younger participants, older volunteers took longer to solve each trial, traversed a longer distance, and made significantly more spatial memory errors. After 5 learning trials, 86% of young and 24% of elderly volunteers were able to locate the goal without error. Performance on the VE navigation task was positively correlated with measures of mental rotation and verbal and visual memory.

工作总结：阿尔茨海默病 (AD) 是几种神经退行性疾病（痴呆）中最常见的一种，主要发生在较晚的年龄，偶尔在 60 岁之前发生，但更常见于 70 岁之后。本研究考察了前瞻性的心理、神经和神经心理学变化巴尔的摩老龄化纵向研究 (BLSA) 的参与者。对 60 岁及以上的参与者进行神经学和神经心理学检查，重复对这些受试者早期进行的许多测试。可能的阿尔茨海默病的诊断遵循 NINCDS-ADRDA 标准。 为了表征与年龄相关的记忆变化和重复测试之间的关系，我们通过分析言语学习和干扰、短延迟和长延迟的测量，研究了纵向变化以及年龄、性别、教育和重复测试对新学习和回忆的影响。自由回忆和提示回忆和识别在单独的混合效应回归中命中。我们发现年龄（p<0.001）和性别（p<0.05）对学习和干扰的横截面影响，无论基线表现如何。年轻人的表现优于老年人，女性的表现优于男性。无论基线分数如何，总学习、长延迟自由和提示回忆都存在纵向年龄变化（p<0.05）。此外，控制基线分数增强了检测短延迟提示回忆和识别命中的纵向年龄变化的敏感性（p<0.05）。重复给药的影响随着总学习和短延迟回忆和长延迟回忆的基线年龄的提高而变化，因此较年轻的基线年龄与随着时间的推移而改善相关，而较老的基线年龄与随着时间的推移而下降相关。受基线年龄影响，与正常衰老相关的语言学习成绩下降。未能考虑到重复测试对衰老的影响可能会降低检测病理衰退的敏感性。 该部门的研究人员开发了一种计算机化方法，根据记忆的纵向变化来帮助预测有患阿尔茨海默病风险的个体，作为临床医生管理潜在痴呆症患者治疗计划的工具。利用视觉记忆表现的初始水平和变化率，我们对 52 名女性和 145 名男性进行了纵向病例对照研究，使用病前视觉记忆测试和神经系统检查来识别患有或不患有痴呆症和 AD 的个体。每个个体的分类方法从第二次检查开始，并根据其余个体的所有后续信息，每次一次检查计算该人的 AD 风险。通过进行交叉验证研究并使用从受试者工作特征 (ROC) 曲线得出的敏感性和特异性的最佳组合，65% 的阿尔茨海默病病例和 75% 的非病例被正确分类为女性，而 65% 的阿尔茨海默病病例被正确分类为女性。男性的病例和非病例的正确分类率分别为 60%。 该部门的研究人员使用虚拟环境（VE）技术来评估人类的空间导航，以量化人类空间导航中与年龄相关的缺陷，并促进认知衰老神经科学的比较方法。我们评估了 VE 中导航行为的年龄差异，并研究了这种导航测量与其他更传统的认知老化测量之间的关系。预训练后，参与者面临 VE 空间学习任务并完成了一系列认知测试。 VE 由一系列纹理丰富的相互连接的走廊组成，一些通向死胡同，另一些通向环境中的指定目标位置。与年轻的参与者相比，年长的志愿者解决每次试验的时间更长，走过的距离更长，并且犯的空间记忆错误明显更多。经过5次学习试验后，86%的年轻人和24%的老年志愿者能够准确无误地找到目标。 VE 导航任务的表现与心理旋转以及言语和视觉记忆的测量呈正相关。