Tracking Alzheimer's Disease

Abstract

Population‐based brain mapping provides great insight into the trajectory of aging and dementia, as well as brain changes that normally occur over the human life span. We describe three novel brain mapping techniques, cortical thickness mapping, tensor‐based morphometry (TBM), and hippocampal surface modeling, which offer enormous power for measuring disease progression in drug trials, and shed light on the neuroscience of brain degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We report the first time‐lapse maps of cortical atrophy spreading dynamically in the living brain, based on averaging data from populations of subjects with Alzheimer's disease and normal subjects imaged longitudinally with MRI. These dynamic sequences show a rapidly advancing wave of cortical atrophy sweeping from limbic and temporal cortices into higher‐order association and ultimately primary sensorimotor areas, in a pattern that correlates with cognitive decline. A complementary technique, TBM, reveals the 3D profile of atrophic rates, at each point in the brain. A third technique, hippocampal surface modeling, plots the profile of shape alterations across the hippocampal surface. The three techniques provide moderate to highly automated analyses of images, have been validated on hundreds of scans, and are sensitive to clinically relevant changes in individual patients and groups undergoing different drug treatments. We compare time‐lapse maps of AD, MCI, and other dementias, correlate these changes with cognition, and relate them to similar time‐lapse maps of childhood development, schizophrenia, and HIV‐associated brain degeneration. Strengths and weaknesses of these different imaging measures for basic neuroscience and drug trials are discussed.