Alzheimer's disease is a neurodegenerative disease causing a progressive decline in the memory, language and motor abilities of individuals affected, leaving them increasingly debilitated and dependent. The high incidence of Alzheimer's Disease is predicted to have a dramatic increase in its prevalence and a commensurate increase in the costs to society. This situation requires the development of improved methods of early detection and identification of subjects likely to progress to full AD so that they might be properly triaged to appropriate therapy. Additionally, new techniques for evaluating potential therapies to slow AD progression are urgently needed so that the most promising therapies are moved rapidly through clinical trials into public use. To study a potential non-invasive imaging method for the detection of the pathological changes occurring in the brains of patients who might develop Alzheimer's disease, this project will test the hypothesis that individuals with mild cognitive impairment (MCI) and with AD will have a shorter T2 in the GM regions of the brain and higher T2 in WM regions of the brain, compared with age and education-matched cognitively normal (CN) individuals. Our broad, long-term goal is to develop image acquisition and analysis tools to measure physiological changes occurring in neurodegenerative diseases. Using image and psychometric data obtained on a large group of individuals followed as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), the project will accomplish three specific aims: (1) To correlate the relaxation time T2 measured from images acquired at 1.5T on a voxel-by-voxel basis across the entire brain with the subject's cognitive status. (2) To correlate the increase in the relaxation rate 1/T2 with magnetic field strength B0 with the subject's cognitive status. (3) To test the power of T2 to predict the probability of conversion from MCI to AD. By comparing the relaxation times and rates of change of subjects who convert to AD with those who remain stable we will build a model relating initial and rates of change of T2 to the probability of conversion to AD. The results of the project will demonstrate that physiological changes in the brain occurring with the progression of Alzheimer's disease can be detected through MRI independently and potentially earlier than brain atrophy is detectable on MR images. Such a non-invasive and sensitive imaging technique will have widespread application in the management and investigation of AD.
This project makes use of a valuable collection of magnetic resonance images and clinical data on a large (800) group of elderly subjects acquired as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). The ADNI subjects are grouped into three categories, cognitively normal, mild cognitively impaired or Alzheimer's diseased and are followed for up to three years using MR imaging and clinical testing. ADNI is the most comprehensive effort to date to identify neuroimaging and other biomarkers of the changes associated with Mild Cognitive Impairment and Alzheimer's Disease. This proposed project will analyze the fast spin echo images acquired on the subjects at each of five study points and on two magnet field strengths to generate images sensitive to iron accumulation and axonal loss. The images will be analyzed using Voxel Based Relaxometry to determine brain sites associated with these physiological changes which accompany the progression of Alzheimer's disease. The research will make particular use of the unique information available from images of the same subjects acquired at two field strengths which will increase the likelihood of detecting an association between iron accumulation and the progression of Alzheimer's disease. The work will stimulate further exploration into the development and application of imaging techniques to provide independent information about the likelihood of Alzheimer's disease progression.
