Early Markers Of Alzheimer Disease

一些在世时没有痴呆症状的人在尸检时有严重的阿尔茨海默病(AD)神经病理。我们调查了患有和不患有AD神经病理的临床正常老年人之间的认知轨迹是否不同，以及在痴呆症诊断之前它们与临床受损个体的轨迹如何比较。巴尔的摩老龄化纵向研究(BLSA)的81名老年参与者在死亡前接受了前瞻性的神经学和神经心理学评估。在痴呆症的临床诊断之前，使用认知数据估计了许多领域的认知变化轨迹。在临床上，患有和不患有AD类型神经病变的老年人在不同的认知域上有相似的认知轨迹。相比之下，轻度认知障碍/阿尔茨海默病患者与临床正常的老年人相比，无论后者是否患有阿尔茨海默病的神经病理，在几个方面的认知纵向减退率都更大。此外，受损和非受损群体之间的认知差异可以在诊断痴呆症的几年前就被检测到。在临床上，患有和不患有阿尔茨海默病神经病变的正常人在许多认知域的认知减退率上没有差别。了解保护某些AD患者免受认知损害的因素可能有助于维持老年人的认知健康。 阿尔茨海默病(AD)研究中的一个长期谜团是，在一些认知正常的人的尸检中发现了大量的A-β斑块。这项研究的重点是无症状阿尔茨海默病(AD)神经元的形态计量学变化，该疾病的特征是在没有认知障碍的受试者中存在AD损害。在尸检脑中，我们用体视学方法比较了无症状AD患者(n=9)、AD痴呆患者(n=8)、轻度认知障碍患者(n=9)和年龄匹配的对照组(n=9)的前扣带回(ACG)和CA1海马神经元的胞体和核体积。在ACG组，我们观察到与对照组相比，MCI和AD的神经元体积显著减少；相比之下，无症状AD组没有出现萎缩。此外，我们还发现，与对照组(P&lt；0.001)、轻度认知障碍组(P&lt；0.01)和AD组(P&lt；0.001)相比，无症状AD组的脑核体积显著增大。在海马区的CA1区也发现了类似的结果。这种核肥大可能代表了神经元对Abeta或Tau的早期反应，或者是一种阻止AD进展并允许大脑抵抗痴呆症发展的代偿机制。我们的结果提供了一个新的发现，与年龄匹配的对照组以及MCI和AD相比，无症状AD患者的ACG和CA1神经元的核肥大。此外，无症状AD患者的神经元胞体体积与无明显AD病理改变的对照组无显著差异。相比之下，AD组和MCI组的神经元胞体体积均明显萎缩。 在HANDLS初步研究参与者中，我们研究了四个不同年龄组：年轻人(18-34岁)、年轻中年人(35-50岁)、中年人(51-)和老年人(年龄&GT；)的总并存分数和特定慢性疾病(包括心血管疾病、肌肉骨骼疾病、糖尿病、中风、高血压和癌症)与几个认知领域的相关性。对384名非裔美国人进行了衡量全球能力、执行功能、记忆功能和知觉速度能力的认知测试。合并症总分是通过计算慢性病的总数来计算的。结果显示，在总样本中，共病总分与执行和记忆功能之间呈负相关。除了最年轻的一组，中风是所有年龄组表现不佳的唯一显著预测因素，但与老年人相比，在较年轻的年龄组中影响更大。这些结果表明，医疗条件对领域特定任务的影响可能会随着年龄的增长而改变。

Some individuals who are asymptomatic for dementia while alive have substantial Alzheimer's disease (AD) neuropathology at autopsy. We investigated whether cognitive trajectories differ between clinically normal elderly individuals with and without AD neuropathology and how they compare with trajectories of clinically impaired individuals before dementia diagnosis. Eighty-one elderly participants in the Baltimore Longitudinal Study of Aging (BLSA) were followed prospectively with neurological and neuropsychological assessments before autopsy evaluation at death. Trajectories of cognitive change were estimated for a number of domains using cognitive data before a clinical diagnosis of dementia. Clinically normal elderly individuals with and without AD-type neuropathology have similar cognitive trajectories across different cognitive domains. In contrast, individuals with mild cognitive impairment/AD show steeper rates of longitudinal decline in several aspects of cognition compared with clinically normal elderly individuals regardless of whether the latter have AD neuropathology. Moreover, the cognitive differences between impaired and unimpaired groups can be detected years before a diagnosis of dementia. Clinically normal individuals with and without AD neuropathology do not differ in rates of cognitive decline across a number of cognitive domains. Understanding the factors that protect some individuals with AD pathology from cognitive impairment may contribute to the maintenance of cognitive health in the elderly. A longstanding riddle in the investigation of Alzheimers disease (AD) has been the finding of substantial numbers of A-beta plaques in the autopsy brains of some individuals with documented normal cognition. This study focuses on the morphometric changes of neurons in asymptomatic Alzheimer's disease (AD), a state characterized by the presence of AD lesions in subjects without cognitive impairment. In autopsy brains, we used stereological methods to compare the cell body and nuclear volumes of anterior cingulate gyrus (ACG) and CA1 hippocampal neurons in asymptomatic AD subjects (n=9), subjects with AD dementia (AD, n=8), mild cognitive impairment (MCI, n=9), and age-matched controls (controls, n=9). In ACG, we observed a significant decrease in the neuronal volume of MCI and AD compared to controls; by contrast, no atrophy was present in asymptomatic AD. Moreover, we found a significant increase in nuclear volume in asymptomatic AD compared to controls (P<0.001), MCI (P<0.01) and AD (P<0.001) brains. Similar results were found in the CA1 region of the hippocampus. This nuclear hypertrophy may represent an early neuronal reaction to Abeta or Tau, or a compensatory mechanism which forestalls the progression of AD and allows the brain to resist the development of dementia. Our results provide a novel finding of nuclear hypertrophy of ACG and CA1neurons in asymptomatic AD in comparison to age-matched controls, as well as MCI and AD. Moreover, the volume of the neuronal cell bodies in asymptomatic AD did not differ significantly from controls without significant AD pathology. By contrast, the volume of the neuronal cell bodies showed significant atrophy not only in AD but also in MCI. In HANDLS pilot study participants, we examined the association of total comorbid score and specific chronic conditions including cardiovascular diseases, musculoskeletal conditions, diabetes mellitus, stroke, hypertension, and cancer with several cognitive domains across four different age groups: young adults (ages 18-34), young middle-aged adults (ages 35-50), middle-aged adults (ages 51-64), and older adults (ages >64). Cognitive tests measuring global ability, executive function, memory function, and perceptual speed ability were administered to 384 African Americans. Total comorbid score was computed by summing up the number of chronic conditions. Results showed an inverse association between total comorbid scores and executive and memory functions in the total sample. With the exception of the youngest group, stroke was the only prominent predictor of poor performance for all age groups, but the impact was greater in the younger age groups compared with older adults. These results suggest that the impact of medical conditions on domain specific tasks may be modified by age.