Brain Imaging In Human Aging, Alzheimer Disease And Rela

人类老龄化：(1)人类的脑血流量和葡萄糖代谢被认为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，在健康男性和女性中，通过正电子发射断层扫描(PET)测量并校正脑萎缩的大脑葡萄糖代谢并没有随着年龄的增长而显著下降。(2)活体脑成像表明，认知加工和注意力可以在早期发育过程中刺激大脑并巩固突触联系。这种巩固可以增加大脑对压力环境的适应性变化，在某些情况下还会促进更具认知能力的灵长类动物的进化。除此之外，年长的受试者对亲属关系的记忆力和贡献也会更大。阿尔茨海默病(AD)：(1)阿尔茨海默病患者的顶叶、颞叶、枕叶、额叶和后扣带回皮质的糖代谢明显低于健康对照组。一年后，阿尔茨海默病患者的顶叶、颞叶、额叶和后扣带回皮质的葡萄糖代谢显著下降。这些发现支持使用PET作为结果衡量标准的可行性，以测试治疗延缓阿尔茨海默病进展的能力。(2)对284例疑似AD患者进行了PET和认知测试的多中心纵向研究。在神经病理确诊的AD病例中，PET模式识别AD患者的敏感性为94%，特异性为73%。最初的正电子发射计算机断层扫描预测后续疾病的概率为0.05。因此，正电子发射计算机断层扫描通常可用于AD或神经退行性疾病患者的早期诊断，而阴性扫描则不太可能患病。(3)通过正电子发射计算机断层扫描(PET)或功能磁共振成像(FMRI)，可以利用刺激强度参数变化的激活来评价AD患者突触的完整性。在接受延迟匹配样本视觉刺激测试的轻度痴呆AD患者中，大脑激活模式与对照组明显不同，因此区分了两组。当反应延迟从1秒增加到16秒时，AD患者的异常AD模式与准确性降低有关，而对照组的准确性在增加的延迟内没有变化。异常的AD-PET图谱提示前额叶皮质和海马区之间的功能脱节。(4)在对患有巴林特综合征的视觉变异型AD患者进行的PET研究中，与健康老龄化相比，矫正萎缩前后视觉区域的大脑葡萄糖代谢降低，而在健康老龄化中，经萎缩校正的新陈代谢没有下降。(5)磁共振成像(MRI)测量的胼胝体前部体积可作为AD患者脑代谢功能障碍的替代指标。在AD患者中，额叶和顶叶皮质脑区的体积缩小与PET测量的葡萄糖代谢降低成比例。(6)AD患者脑组织N-乙酰天冬氨酸浓度降低，肌醇和肌酸浓度升高。由于后者的升高在轻度痴呆的AD患者中具有统计学意义，1H-MRS可用于诊断早期AD。(7)在唐氏综合征痴呆前期，随着年龄的增长，内侧颞叶结构的体积发生显著变化，并与记忆有关。这些结构在唐氏综合征的阿尔茨海默病早期就会受到影响，它们的评估可能有助于识别处于阿尔茨海默病临床前阶段的人。

Human Aging: (1) Human brain blood flow and glucose metabolism have been considered to decline with age, suggesting reduced brain functional activity. However, we showed 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. (2) In vivo brain imaging suggests that cognitive processing and attention can stimulate the brain and consolidate synaptic connections during early development. This consolidation can increase brain adaptive changes to a stressful environment, and in some cases promote evolution of more cognitively capable primates. Added to this can be the greater memory and contribution of older subjects to kinships. Alzheimer disease (AD): (1) The patients with Alzheimer's disease had significantly lower glucose metabolism than healthy comparison subjects in parietal, temporal, occipital, frontal, and posterior cingulate cortices. One year later, the patients with Alzheimer's disease had significant declines in glucose metabolism in parietal, temporal, frontal, and posterior cingulate cortices. These findings support the feasibility of using PET as an outcome measure to test the ability of treatments to attenuate the progression of Alzheimer's disease. (2) A multicenter longitudinal study was conducted on 284 suspected AD patients who underwent PET and cognitive testing. In neuropathologically confirmed AD cases, PET patterns identified patients with AD with a sensitivity of 94% and a specificity of 73%. The initial PET scan predicted subsequent disease with a probability of < 0.05. Thus, PET can be used for the early diagnosis of patients with AD or neurodegenerative disease generally, with a negative scan making the likelihood of disease unlikely. (3) Activation 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). Brain activation in mildly-demented AD patients presented with a delayed match-to-sample visual stimulus test demonstrated a significantly different pattern from the pattern in control subjects, thus distinguishing the two groups. The abnormal AD 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 within increasing delay. The abnormal AD PET pattern suggested functional disconnection between prefrontal cortex and hippocampus. (4) In a PET study of patients with a visual variant of AD, having Balint's syndrome, brain glucose metabolism was reduced in visual areas before and after atrophy correction, compared with healthy aging where metabolism corrected for atrophy does not decline. (5) The volume of the anterior corpus callosum, measured with magnetic resonance imaging (MRI), was shown to be a surrogate marker of brain metabolic dysfunction in AD. In AD patients, its volume was reduced in proportion to reduced glucose metabolism, measured with PET, in frontal and parietal cortical brain 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. (7) In the predementia phase of Down's syndrome, significant volume changes in medial temporal lobe structures occur with age and are related to memory. These structures are affected early in Alzheimer's disease in Down's syndrome, and their evaluation may help identify people in the preclinical stages of Alzheimer's disease.