Magnetic resonance imaging in Alzheimer's disease: from diagnosis to measuring therapeutic effect

Research into magnetic resonance imaging (MRI) in Alzheimer's disease (AD) is entering a new era driven by the advent of treatments for AD. Historically the purposes of the brain scan in an individual with a provisional diagnosis of AD were limited to excluding treatable structural lesions and assessing the extent of ischaemic changes. Over the last decade progress has been made in identifying imaging features that have positive predictive value in AD. Progressive atrophy of the hippocampus and other medial temporal lobe structures have now been consistently shown to be characteristic of AD. A range of techniques for assessing atrophy of medial temporal lobe structures have been developed from simple visual rating scales to more sophisticated volumetric measurements. These methods have shown the hippocampus to be reduced in size from early in the disease. Furthermore hippocampal atrophy may predict progression to dementia in individuals at risk of the disease by virtue of memory impairment or family history. Nonetheless, despite advances in scanning and in image analysis, these measures still show considerable overlap between normal aging and early AD. MRI has a role to play in the differential diagnosis in a patient with dementia: focal or asymmetrical atrophy on MRI argues against a diagnosis of AD and in favour of a diagnosis such as fronto-temporal dementia. However MRI features that accurately distinguish the non-focal degenerative dementias, one from another (e.g. dementia with Lewy bodies from AD) are still lacking. The availability of symptomatic treatments in AD further increases the pressure for imaging measures which are sensitive and specific in early disease. Research into improving early diagnosis remains very active and the development of potentially disease-modifying therapies adds a new focus to MRI research in AD. Accurate measurement of progression and the development of markers which distinguish disease-modifying from symptomatic effects is likely to be an important new area of research. MRI will be central to these developments but may face competition from functional imaging.