Early Markers Of Alzheimer Disease

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。 为了描述年龄相关的记忆变化和重复测试之间的关系，我们调查了纵向变化和年龄，性别，教育和重复测试对新的学习和回忆的影响，通过分析言语学习和干扰，短期和长期延迟的自由和线索回忆和识别命中单独的混合效应回归的措施。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，与基线表现无关。年轻人的表现优于老年人，女性的表现优于男性。无论基线得分如何，总学习、无长延迟记忆和线索回忆都存在纵向年龄变化（p<0.05）。此外，控制基线分数提高了检测短时延线索回忆和再认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基线年龄的增加而变化，总学习和短期和长期延迟回忆，因此较年轻的基线年龄与随时间的改善相关，而较年长的基线年龄与随时间的下降相关。语言学习能力的下降与受基线年龄影响的正常衰老有关。如果不考虑重复检测对衰老的影响，可能会降低检测病理性衰退的灵敏度。 部分研究人员开发了一种计算机化的方法，以帮助预测个人在发展阿尔茨海默病的风险的基础上纵向变化的记忆作为工具，临床医生在管理潜在的痴呆症AD患者的治疗计划。使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，使用视觉记忆和神经系统检查的病前测试来识别患有和不患有痴呆症和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随访信息，一次一次地进行一次检查，以计算该人的AD风险。通过进行交叉验证研究，并使用来自受试者工作特征（ROC）曲线的灵敏度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%和60%的病例和非病例，分别被正确分类为男性。 部分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，并促进认知老化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，并研究了这种导航措施和其他更传统的认知老化措施之间的关系。在预训练之后，参与者面临着VE空间学习任务，并完成了一系列认知测试。虚拟环境由一系列纹理丰富的相互连接的走廊组成，一些走廊通向死胡同，另一些则通向环境中指定的目标位置。与年轻的参与者相比，年长的志愿者需要更长的时间来解决每个试验，穿越更长的距离，并产生更多的空间记忆错误。经过5次学习试验，86%的年轻志愿者和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、言语记忆和视觉记忆呈正相关。

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.