Progression of Atrophy in Alzheimer’s Disease and Related Disorders

Jennifer L. Whitwell

Longitudinal MRI is a powerful tool that allows the assessment of progression of brain changes over multiple imaging time-points and has been increasingly employed in the study of neurodegenerative dementias, particularly Alzheimer's disease (AD). Early studies demonstrated that AD was associated with increased rates of whole brain loss and hippocampal atrophy. A number of sophisticated voxel-level techniques have now been developed that have provided additional information describing regional atrophy over time in the temporal, parietal, and frontal lobes in AD. Studies have also focused on subjects in the prodromal phase of AD in order to describe the earliest changes that are occurring in the brain. Atrophy has been shown to start in the medial temporal lobes and fusiform gyrus at least 3 years before subjects reach a diagnosis of AD, and then spread to the posterior temporal lobes and parietal lobes, and then eventually the frontal lobes. These patterns of atrophy correlate well with the progression of neurofibrillary tangles observed on pathology. Rates of atrophy have also been shown to accelerate over the course of the disease as a subject progresses from cognitively normal to a diagnosis of AD. Similar techniques have also been applied to other neurodegenerative diseases, such as frontotemporal dementia which show higher rates of atrophy and different patterns of progression to those observed in AD. Hence, longitudinal MRI shows promise as a biomarker of disease progression in neurodegenerative disease.