COGNITIVE & NEUROPHYSIOLOGICAL FUNCTION IN HEALTHY AGING

两个家庭的光学纹理被动地提供给健康志愿者进行正电子发射断层扫描（PET），以测量局部脑血流量（rCBF）：随机纹理，其中黑色和白色检查安排在一个随机的方式，甚至纹理，其中的检查被命令产生扩展的轮廓和矩形块在多个空间尺度。在年轻受试者中，随机和均匀纹理的重复交替呈现在最初的呈现中显示了纹状皮层的差异rCBF激活，在随后的呈现中显示了纹外联合视觉区，在最终呈现中显示了海马体，这表明大脑可以学习对视觉模式的差异进行分类，而无需直接有意识的参与。 在老年健康对照组中，纹外区和额叶区域被激活，而在年轻受试者中没有被激活，这表明随着年龄的增长，视觉感知过程中皮质资源的重新分配。在年轻的健康受试者中，毒扁豆碱（一种乙酰胆碱酯酶抑制剂）改善了面孔工作记忆任务的表现，表现为减少了任务的反应时间，并减少了右前额叶皮层PET测量的rCBF的任务特异性增量。 相关性分析表明，提高的性能涉及的功能改变区域的皮层网络subserving知觉加工，记忆和注意。 阿尔茨海默病（AD）：与典型AD患者相比，具有早期显著视觉障碍的阿尔茨海默病（AD）患者亚组显示脑葡萄糖代谢低下，用PET测量并校正顶枕叶和距状皮质的萎缩，边缘区相对保留。 在这个亚组中，尸检病理学显示老年斑和神经纤维缠结的分布与代谢缺陷的模式一致。对照组和AD患者的rCBF在大脑视觉区的变化，以响应增加频率的视觉呈现的图案闪光。在纹状皮层，rCBF从0到8 Hz增加，然后下降，而在纹外视皮层，rCBF单调增加，从0到16 Hz。轻度痴呆AD患者的血流反应异常，中度和重度痴呆患者更是如此，提示早期和进行性突触功能障碍。在对照组和AD患者中，用PET测量静息时和对视觉激活的反应时的脑葡萄糖代谢。 轻度痴呆患者的活化代谢反应在正常范围内，但在更严重的痴呆患者中降低。 反应性下降可能是中重度痴呆AD患者神经递质替代治疗成功率有限的原因。 在AD的初始阶段对活化的“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的下调。 在后期阶段的反应性降低归因于与神经元死亡和神经元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）测量的胼胝体尺寸减小可用作AD中代谢和认知功能障碍的标志物。 研究表明，连接左右大脑半球的胼胝体的大小与左右额叶和顶叶的PET测量的大脑代谢减少成比例下降。

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.