In vivo MRI markers of cognitive decline in the elderly

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by a gradual decline of various cognitive processes, ultimately resulting in dementia. One major component of the cognitive decline is difficulty in performance of declarative memory. The hippocampus and entorhinal cortex are two structures thought to be involved in this type of memory function. The entorhinal cortex relays multimodal sensory information to the hippocampus, via the perforant pathway. Therefore, damage to any component of this network could disrupt declarative memory function. Early detection of damage to these structures is important so that the earliest possible interventional strategies can be applied to slow or stop this disease. Detection of changes to the hippocampus and entorhinal cortex is now possible in vivo using high resolution magnetic resonance imaging (MRI). The work in this dissertation uses quantitative MRI techniques [hippocampal and entorhinal volume along with whole brain voxel based morphometry (VBM)] to develop structural markers of early AD. The data show that baseline volume and rates of atrophy of the hippocampus and entorhinal cortex predict cognitive decline in individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI) and very mild AD. However, the entorhinal cortex baseline volume and rate of atrophy was associated with a greater risk, than the hippocampus, of development of AD from a nondemented state (i.e. NCI and MCI). In addition, VBM revealed atrophy in the hippocampal gray matter and parahippocampal gyrus gray and white matter. These findings show that not only are the hippocampus and entorhinal cortex effected in incipient and early AD but also the white matter connections between these two structures. To test how these changes in gray and white matter relate to the declining memory in incipient and mild AD, memory scores were correlated with longitudinal and VBM atrophy measures. The results showed that hippocampal, entorhinal cortex and white matter atrophy all correlate with declarative memory scores in NCI, MCI, and AD. The findings in these studies show the early predictive value of MRI derived structural markers of AD and how closely related these markers are to the memory dysfunction associated with the disease.