Component diffusion tensor analysis suggests disparate temporal stem and fornix white matter pathology in Mild Cognitive Impairment
Alzheimer’s disease (AD) is the most common type of dementia. The progressive development of specific cognitive deficits, initially affecting short-term memory and spreading to more global cognitive decline, is paralleled by the progressive deterioration of specific brain regions. In this way, function and structure are intricately linked in disease progression. Successful identification of individuals with very early probable AD would have major implications for targeting research into prevention or treatment of AD. Mild Cognitive Impairment (MCI) is a clinical condition representing the transition state from normal cognitive aging to AD. Investigation of individuals with this condition provides an opportunity to assess factors that predict the course of neurodegeneration. Diffusion tensor imaging (DTI) has become increasingly common in the in vivo investigation of the structural integrity of biological tissue. This Magnetic Resonance Imaging (MRI) method captures the varied propensity of water molecules to diffuse in tissue, making it possible to characterize the type, structure, and integrity of the tissue. Using DTI, we investigated the diffusivity in multiple regions of interest (ROIs) in the brain in individuals with MCI. We employed both commonly used, summative metrics of the diffusion tensor, fractional anisotropy (FA) and mean diffusivity (MD), as well as components of the diffusion tensor, axial diffusivity (DA) and radial diffusivity (DR) in these regions. We also investigated the relationships between regionally specific DTI measures and neuropsychological measures of memory. We present data suggesting that integrity of the white matter (WM) of the limbic system, specifically the fornix, is reduced in the early stages of neurodegeneration observed in MCI. We also present data which indicate fornix integrity is linked to specific decrements in a neuropsychological measure known to be selectively sensitive to coordinated parahippocampal activity. Lastly, we present data suggesting that the fornix WM has a disparate pathological profile from temporal stem (TS) WM, regions known to be affected early and severely in AD and MCI pathobiology. Specifically, poor performance on this memory task was selectively associated with lower FA, higher MD, and lower DR but not DA in the fornix, while the exact inverse was found for TS WM (association with higher DA but not FA, MD, or DR). The studies herein provide evidence of the utility of combining clinical and diffusion neuroimaging methods in the evaluation of early cognitive changes in MCI. Further, they highlight the advantages of evaluating the full tensor, not just FA or MD, in elucidating potential pathology in the tissue being imaged. Establishing the structure-function relationships in early MCI and AD pathology may help identify individuals at particularly high risk for progression to AD. The long-term goal of this research is to better inform the development of targeted interventions that will reduce the substantial morbidity and mortality rates and public health burden of AD.
Neurology, Mild Cognitive Impairment, Alzheimer's disease, Diffusion Tensor Imaging, Fornix, Associative Learning, Disconnection Syndrome
Networked Digital Library of Theses and Dissertations