Corpus callosum in aging and dementia.

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.