Multimodal techniques for diagnosis and prognosis of Alzheimer's disease

a, Relationship of PIB PET to cerebrospinal-fluid Ab₄₂ concentration in cognitively normal individuals. Subjects with mean cortical PIB binding potentials >0.16 (calculated from an average of PIB retention in the prefrontal cortex, the lateral temporal cortex, the precuneus and the gyrus rectus, divided by PIB retention in the cerebellar cortex) are considered PIB-positive and uniformly have low CSF Ab₄₂ concentrations (<500 pg ml^-1); PIB-negative subjects with low Ab₄₂ concentrations may have non-fibrillar (diffuse) Ab₄₂ deposits that do not retain PIB. Whether non-demented individuals with high PIB and/or low cerebrospinal-fluid Ab₄₂ are more likely to develop dementia than those with low PIB and/or high cerebrospinal-fluid Ab₄₂ has not yet been reported on for large numbers of people, but an initial study supports this idea. b, Axial (horizontal) view of Alzheimer's brain, imaged to quantify amyloid (PIB PET), annual rates of regional atrophy (quantitative MRI) and hypometabolism in relation to dementia severity (fluorodeoxyglucose PET). The intensity of the PIB binding potential is depicted using a colour scale (approximated by the colours in a) in which red reflects greatest PIB retention, and black and dark blue reflect least PIB retention. The regional extent of atrophy is depicted colorimetrically, with rates ranging from 0.4% per year (dark blue) to 1% per year (yellow/green). Regional hypometabolism is also depicted colorimetrically, with red and yellow representing greater and lesser hypometabolism, respectively. The units of this scale reflect the slope of the regression between hypometabolism and dementia severity as measured by mini-mental status examination; high slope suggests a steeper decline in metabolism in relation to decreasing cognitive ability. c, Illustrations of left hemi-brain surfaces (medial, left; lateral, right), allowing comparison of averaged anatomical signal maps for amyloid (top), atrophy (second from top), hypometabolism (third from top) and default-network activity (bottom). Regional amyloid load (PIB binding potential) is depicted as percentage increase of PIB binding potential over that of the brainstem, ranging from 5% (red) to 40% (yellow/white). Colorimetric scales for atrophy and hypometabolism are as in b. The colour scale for regional default-network activity shows the degree of association, ranging from greatest association with default-network activity (light blue) to least statistically significant association (darker blue).