Frederiksen Kristian Steen
Danish Dementia Research Center, Department of Neurology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Dan Med J. 2013 Oct;60(10):B4721.
The overarching objective of the thesis was to investigate the morphological changes in the corpus callosum (CC) in aging and dementia in relation to its role in cognitive and motor decline. The CC is the largest white matter tract in the brain, containing upwards of 200 million axons, and is believed important for communication and interaction between the two cerebral hemispheres. Historically, the role of white matter, including the CC, in relation to cognitive function has often been eclipsed by the predominance of the cortex, and led to a "corticocentric" view of the brain and cognitive function. However, from the 1960s and onwards, the role of lesions in the white matter in the appearence of cognitive deficits and diseases such as dementia has become increasingly evident. Many studies have indicated that AD is associated with CC atrophy, but the precise pattern of subregional CC atrophy in different disease stages remains undetermined. In study I, we establish that atrophy is present primarily in the posterior CC early in AD, and that atrophy of the CC is associated with faster disease progression. This finding supports a model where posterior atrophy is the earliest changes in the CC in AD patients, with atrophy of anterior CC being a later pathological event. To further elucidate the role of CC atrophy in dementia, we examined a population of 329 elderly subjects, and found that a higher rate of tissue loss in posterior CC is associated with an increased risk of dementia. This study represents the first to examine CC in elderly subjects longitudinally. In the same cohort, we investigated whether impairment in specific cognitive domains was associated with CC tissue loss. Previous studies had shown that processing speed and executive functions may be particularly reliant on the CC. Our findings indicated that CC tissue loss leads to selective impairment of processing speed but not memory or executive function deficits. Finally, CC tissue loss was also associated with impairment of motor function. Overall, the present findings confirm and extend the role of the CC in dementia and age-associated cognitive and motor deficits.
本论文的总体目标是研究胼胝体（CC）在衰老和痴呆过程中的形态变化，及其与认知和运动功能衰退的关系。CC是大脑中最大的白质束，包含超过2亿条轴突，被认为对两个大脑半球之间的交流和互动至关重要。从历史上看，包括CC在内的白质在认知功能方面的作用，常常因皮质的主导地位而被忽视，从而导致了对大脑和认知功能的“以皮质为中心”的观点。然而，从20世纪60年代起，白质病变在认知缺陷和痴呆等疾病表现中的作用日益明显。许多研究表明，阿尔茨海默病（AD）与CC萎缩有关，但不同疾病阶段CC亚区域萎缩的精确模式仍未确定。在研究I中，我们确定AD早期萎缩主要出现在CC后部，且CC萎缩与疾病进展加快有关。这一发现支持了一种模型，即后部萎缩是AD患者CC最早的变化，而前部CC萎缩是后期的病理事件。为了进一步阐明CC萎缩在痴呆中的作用，我们对329名老年受试者进行了研究，发现CC后部较高的组织丢失率与痴呆风险增加有关。这项研究是首次对老年受试者的CC进行纵向研究。在同一队列中，我们调查了特定认知领域的损害是否与CC组织丢失有关。先前的研究表明，处理速度和执行功能可能特别依赖于CC。我们的研究结果表明，CC组织丢失会导致处理速度的选择性损害，但不会导致记忆或执行功能缺陷。最后，CC组织丢失也与运动功能损害有关。总体而言，目前的研究结果证实并扩展了CC在痴呆以及与年龄相关的认知和运动缺陷中的作用。
