Brain Imaging In Human Aging And Alzheimer Disease

人类衰老：（1）功能性磁共振成像（fMRI）检测了人类受试者的脑血流激活区域，这些受试者被呈现了不同密度特征的视觉纹理模式，如轮廓和块。视觉（纹状）皮层中的血流激活和纹理密度之间的线性关系表明，某些纹状皮层神经元具有从图像中提取和处理视觉纹理的内在能力。(2)大约40年来，人们一直认为人脑血流量和葡萄糖代谢会随着年龄的增长而下降，这表明大脑功能活动减少。然而，我们发现，在“静息状态”下通过正电子发射断层扫描（PET）测量并校正脑萎缩的脑葡萄糖代谢，在健康男性和女性中并没有随着年龄的增长而显著下降。因此，在没有脑部疾病的情况下，每克实际大脑的大脑能量代谢是年龄不变的（与疾病减少相反，见下文）。 阿尔茨海默病（AD）：（1）伴有明显视觉障碍的AD患者（Balint综合征）在脑萎缩校正代谢前后的PET上显示脑视觉区葡萄糖代谢低下。病理性老年斑和神经元缠结被发现在死后的低代谢领域。因此，与健康老龄化不同，由于潜在的神经病理学，AD中的内在脑代谢即使在萎缩校正后也会降低。(2)一项涉及NIA脑生理学和代谢科的多中心纵向研究对284名接受PET和认知测试的疑似AD患者进行了研究。在神经病理学证实的病例中，PET模式识别AD或任何神经退行性疾病患者的灵敏度为94%，特异性分别为73%和78%。在一次阴性的脑部PET扫描后，进展性与非进展性病程的可能性为0.10。最初的PET扫描预测后续疾病的概率为0.001。因此，PET可用于AD或神经退行性疾病患者的早期诊断。阴性扫描使疾病的存在极不可能。(3)激活范例，其中刺激强度是变化的参数，可用于评估突触的完整性，在AD患者的PET或功能性磁共振成像（fMRI）。激活扫描可用于表征AD的过程，评估药物疗效，进行早期诊断，并在临床痴呆出现之前识别遗传风险受影响的受试者。(4)在接受延迟匹配样本视觉刺激测试的受试者中，轻度痴呆AD和对照受试者的大脑激活表现出不同的模式，从而区分了两组。AD患者的异常模式与准确性降低相关，因为反应延迟从1秒增加到16秒，而对照组的准确性没有变化。AD PET图像异常提示前额叶皮层与海马的功能性分离。(5)通过磁共振成像（MRI）测量的胼胝体前部体积是AD患者脑代谢功能障碍的替代标志物。在AD患者中，其大小与额叶和顶叶皮质区域的葡萄糖代谢减少成比例减少，用PET测量。(6)在AD患者中，1H-磁共振波谱（MRS）与外部标准显示，脑内N-乙酰天冬氨酸浓度降低，但肌醇和肌酸浓度增加。由于后者的增加在轻度痴呆AD患者中具有统计学意义，因此1H-MRS可用于早期AD的诊断。

Human Aging: (1)Functional magnetic resonance imaging (fMRI) detected areas of brain blood flow activation in human subjects who were presented visual texture patterns that differed in the density of features, such as contours and blocks. A linear relation between blood flow activation in the visual (striate) cortex and the density of the textures indicated that certain striate cortical neurons have an intrinsic ability to extract and process visual textures from an image. (2) For some 40 years, human brain blood flow and glucose metabolism have been considered to decline with age, suggesting reduced brain functional activity. We showed, however, that brain glucose metabolism, measured by positron emission tomography (PET) in the " resting state" and corrected for brain atrophy, did not decline significantly with age in healthy men and women. Thus, brain energy metabolism per gram actual brain is age-invariant in the absence of brain disease (in contrast to its being reduced with disease, see below). Alzheimer disease (AD): (1) AD patients with prominent visual disturbances (Balint's syndrome) showed glucose hypometabolism in brain visual areas on PET, before and after metabolism was corrected for brain atrophy. Pathological senile plaques and neurofibrillary tangles were found postmortem in the hypometabolic areas. Thus, unlike healthy aging, intrinsic brain metabolism even after atrophy correction is reduced in AD due to underlying neuropathology. (2) A multicenter longitudinal study, involving the Section on Brain Physiology and Metabolism at the NIA, was conducted on 284 suspected AD patients who underwent PET and cognitive testing. In neuropathologically confirmed cases, the PET patterns identified patients with AD or any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The likelihood of a progressive versus nonprogressive course following a single negative brain PET scan was 0.10. The initial PET scan predicted subsequent disease with a probability of 0.001. Thus, PET can be used for the early diagnosis of patients with AD or neurodegenerative disease generally. A negative scan makes the existence of disease highly unlikely. (3) Activation paradigms in which stimulus intensity is varied parametrically can be used to evaluate synaptic integrity in AD patients by means of PET or functional magnetic resonance imaging (fMRI). Activation scanning can be used to characterize the course of AD, to evaluate drug efficacy, to make an early diagnosis, and to identify genetically at-risk affected subjects prior to appearance of clinical dementia. (4) Brain activation in subjects who were presented a delayed match-to-sample visual stimulus test demonstrated different patterns in mildly-demented AD and control subjects, thus distinguishing the two groups. The abnormal pattern in the AD patients was associated with reduced accuracy as response delay was increased from 1 to 16 seconds, whereas accuracy was unchanged in the controls. The abnormal AD PET pattern suggested functional disconnection between prefrontal cortex and hippocampus. (5) The volume of the anterior corpus callosum, measured with magnetic resonance imaging (MRI), is a surrogate marker of brain metabolic dysfunction in AD. In AD patients, its size was reduced in proportion to reduced glucose metabolism, measured with PET, in frontal and parietal cortical regions. (6) In AD patients, 1H-magnetic resonance spectroscopy (MRS) with external standards demonstrated a reduced brain concentration of N-acetylaspartic acid but increased concentrations of myoinositol and creatine. As the latter increases were statistically significant in mildly demented AD patients, 1H-MRS can be used to diagnose early AD.