COGNITIVE & NEUROPHYSIOLOGICAL FUNCTION IN HEALTHY AGING

两类光学纹理被被动呈现给接受正电子发射断层扫描（PET）测量区域脑血流（rCBF）的健康志愿者：随机纹理，其中黑白方格以随机方式排列，均匀纹理，其中方格被命令在多个空间尺度上产生扩展轮廓和矩形块。在年轻受试者中，随机和均匀纹理的反复交替呈现在初始呈现时，纹状皮层的rCBF激活不同，在随后的呈现中，纹状皮层的rCBF激活不同，在最后的呈现中，纹状皮层的rCBF激活不同，海马体的rCBF激活不同，这表明大脑可以在没有直接意识参与的情况下学会对视觉模式的差异进行分类。在年龄较大的健康对照中，年轻受试者未激活的脑外和额叶区域被激活，这表明随着年龄的增长，视觉感知过程中皮层资源的重新分配。年轻健康受试者,毒扁豆碱乙酰胆碱酯酶抑制剂,改进的性能在working-memory-for-faces任务,任务被视为减少反应时间,并降低特定于任务的增量与宠物rCBF测量正确的前额叶皮层。相关分析表明，表现的改善涉及控制知觉加工、记忆和注意的皮质网络的功能改变区域。阿尔茨海默病（AD）：与典型的阿尔茨海默病患者相比，阿尔茨海默病（AD）患者中有一个亚组，早期有明显的视觉障碍，在顶枕皮质和脑钙皮质显示脑葡萄糖代谢低下，PET测量并纠正萎缩，旁边缘区相对较少。在这个亚组中，死后病理显示老年斑和神经原纤维缠结的分布与代谢缺陷的模式一致。对照和AD患者的rCBF随着视觉呈现模式闪烁频率的增加而改变。纹状皮层rCBF在0 ~ 8 Hz范围内先增加后减少，而纹状外视觉皮层rCBF在0 ~ 16 Hz范围内单调增加。轻度痴呆AD患者血流反应异常，中重度痴呆患者血流反应异常更为明显，提示早期和进行性突触功能障碍。在对照组和阿尔茨海默病患者静息时用PET测量脑葡萄糖代谢，以及对听觉-视觉激活的反应。激活的代谢反应在轻度痴呆患者中处于正常范围内，但在重度痴呆患者中有所降低。反应性下降可能解释了神经递质替代疗法在AD合并中重度痴呆患者中的有限成功。在阿尔茨海默病的初始阶段，对激活的“正常”代谢反应归因于介导线粒体氧化磷酸化的脑酶的选择性和潜在可逆下调。晚期反应性降低归因于与神经元死亡和神经原纤维缠结形成相关的线粒体功能的不可逆丧失。使用磁共振成像（MRI）测量胼胝体大小的减小，可以作为AD患者代谢和认知功能障碍的标志。连接左右大脑半球的胼胝体的大小与左右额叶和顶叶的脑代谢减少成正比。

Two families of optical textures were passively presented to healthy volunteers undergoing positron emission tomography (PET) to measure regional cerebral blood flow (rCBF): Random textures in which black and white checks were arranged in a random fashion, and Even textures in which the checks were ordered to produce extended contours and rectangular blocks at multiple spatial scales. In young subjects, repeated alternating presentation of Random and Even textures showed differential rCBF activation in striate cortex in initial presentations, of extrastriate association visual areas in subsequent presentations, and of hippocampus in final presentations, suggesting that the brain can learn to classify differences in visual patterns without direct conscious involvement. In older healthy controls, extrastriate and frontal regions were activated that were not activated in the young subjects, suggesting a reallocation of cortical resources during visual perception with age. In young healthy subjects, physostigmine, an acetylcholinesterase inhibitor, improved performance on a working-memory-for-faces task, seen as a reduced reaction time on the task, and reduced task-specific increments in rCBF measured with PET in the right prefrontal cortex. A correlation analysis showed that the improved performance involved functional alterations regions in cortical networks subserving perceptual processing, memory and attention. Alzheimer disease (AD):A subgroup of Alzheimer disease (AD) patients with early prominent visual disturbances showed cerebral glucose hypometabolism, measured with PET and corrected for atrophy, in parieto-occipital and calcarine cortices, with relative sparing of paralimbic regions, compared to typical AD patients. In this subgroup, postmortem pathology showed a distribution of senile plaques and neurofibrillary tangles consistent with the pattern of metabolic deficits. rCBF in control and AD patients changed in brain visual areas in response to increasing frequency of visually presented pattern flashes. In striate cortex, rCBF increased from 0 to 8 Hz, then decreased, whereas in extrastriate visual cortex, rCBF increased monotonically from 0 to 16 Hz. Flow responses were abnormal in mildly demented AD patients, more so in moderately and severely demented patients, suggesting early and progressive synaptic dysfunction. Brain glucose metabolism was measured with PET at rest and in response to auditory-visual activation in controls and AD patients. The activated metabolic response was within normal limits in mildly demented patients but was reduced in more demented patients. Declining responsiveness may account for limited success of neurotransmitter replacement therapy in AD patients with moderate-severe dementia. A "normal" metabolic response to activation in initial stages of AD was ascribed to selective and potentially reversible downregulation of brain enzymes that mediate mitochondrial oxidative phosphorylation. Reduced responsiveness in later stages was ascribed to irreversible loss of mitochondrial function associated with neuronal death and neurofibrillary tangle formation. Reduced size of the corpus callosum, measured using magnetic resonance imaging (MRI), can be used as a marker of metabolic and cognitive dysfunction in AD. The size of the corpus callosum, which connects right and left cerebral hemispheres, was shown to fall in proportion to reduction in brain metabolism measured with PET in left and right frontal and parietal lobes.