Aβ amyloid deposition in the language system and how the brain responds

Abstract

Post-mortem measures of Aβ amyloid deposition correlate only weakly with cognitive dysfunction antemortem. We tested the hypothesis that functional reorganization forms a critical intermediary step between Aβ amyloid-associated brain injury and clinical disease expression. Fifteen patients with early-stage probable Alzheimer's disease (AD) and 16 cognitively intact controls participated in this combined functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) study. The fMRI design had two factors: task (associative-semantic versus visuoperceptual judgement) and input-modality (written words versus pictures). We measured Aβ amyloid by means of Pittsburgh Compound B (11C-PIB). In the posterior third of the left superior temporal sulcus (STS), the fMRI response during the associative-semantic compared with the visuoperceptual task was lower in AD than in controls, in particular for words. Response amplitude correlated inversely with PIB uptake in this region. Contralaterally, the functional pattern differed substantially: the fMRI response in the right posterior STS during the associative-semantic versus the visuoperceptual task was higher in AD than in controls. Accuracy on the Boston Naming test correlated positively with the degree to which AD patients were able to recruit the right STS (r = 0.84, P corrected = 0.014). PIB uptake did not correlate with naming accuracy. Functional reorganization of the language system in response to Aβ amyloid-related brain injury exists in early-stage AD and determines the degree of anomia more than Aβ amyloid load per se does. © 2007 The Author(s).