| As our population ages and therapies become available to retard Alzheimer's Disease (AD), it will be increasingly important to identify individuals at risk for progression to AD. Amnestic Mild Cognitive Impairment (MCI) is a term used to describe individuals who have objective loss, do not meet criteria for dementia and yet are at high risk for progressing to AD. The purpose of this thesis was threefold: (1) to characterize behavioural performance and patterns of fMRI activation during encoding and retrieval while manipulating levels of processing in normal elderly; (2) to characterize differences between amnestic MCI (n = 14) and normal controls (NC) (n = 14) using the same memory manipulation; and (3) to utilize in-vivo, multimodal, functional and structural brain imaging techniques and neuropsychological profile to discriminate MCI from normal aging. Results. fMRI in NC revealed that the medial temporal lobe (MTL) is important for establishing new memories and successful retrieval. Although MCI did not show differences in MTL activation during deep encoding compared to NC, bilateral inferior frontal activation was decreased, suggesting early compromise in this region or in its connection to the MTL. Planimetric tracing on MRI of MCI showed reduced volume of the left entorhinal cortex, right superior temporal gyrus and the width of the MTL (MTLT) bilaterally. SPECT perfusion measurements referenced to the cerebellum, showed a reduction in perfusion ratios in regions that are connected to the MTL, such as the right posterior cingulate and lateral anterior temporal lobe bilaterally, as well as in the left inferior frontal gyrus and precuneus bilaterally. These regions may be undergoing neuropathological changes due to a reduction in neuronal input from the MTL or may be degenerating themselves. Finally, models that include measures such as the left MTLT with a perfusion ratio in the right posterior cingulate, along with performance on confrontational naming was differentiating MCI from NC by 100%, as was a model including delayed non-verbal recall and confrontational naming. These findings will be important in determining which measures may be best at predicting progression to AD in MCI, which was not possible in this small sample. |
