MRI measures of brain integrity and their relation to processing speed in the elderly

A significant percentage of the elderly population experiences at least one geriatric disability. Previous studies have shown that geriatric disabilities are preceded by sub-clinical cognitive changes of aging and brain changes seen on magnetic resonance imaging (MRI). Decreased information processing speed has been identified as a common factor associated with age-related disabilities in gait, cognition, and mood. However, the current neurocognitive model of aging is incomplete; there remains uncertainty about the relationships between the different components of brain integrity and cognitive function. The goals of this dissertation are to characterize the relationships between different functional and structural MRI markers (for example: macro-structural, micro-structural, physiologic) with respect to cognitive aging and to improve the neuroimaging toolset for oldest old.;We studied the relationship between functional MRI markers, structural MRI markers, and information processing speed in a sample of twenty-five healthy elderly subjects. We found that recruitment of fronto-parietal brain areas was associated with higher performance. Also, greater structural damage (white matter integrity) was associated with lower activation in prefrontal and anterior cingulate regions. In the presence of underlying brain connectivity structural abnormalities, additional posterior parietal activation was found to be important for maintaining higher task performance.;We also studied MRI measures of brain structure in a sample of 277 community-dwelling older adults free from neurological diseases. This study used a set of neuroimage analysis pathways optimized for the MRI images and examined the macro- and micro-structural indices. The results indicate that both the macro- and micro-structural MRI indices may provide complementary information on neuroanatomical correlates of information processing speed. The micro-structural MRI indices of white matter integrity were found to be the strongest correlate of information processing speed in this sample.;While developing the image analysis pipelines for this dataset, we noticed that the diffusion tensor-imaging pathway was particularly sensitive to the approach of localizing the white matter tracts. We used both empirical and simulated datasets to confirm our hypothesis that the mean fractional anisotropy of the white matter tract is more sensitive to individual differences in the elderly when compared to a skeleton based approach.