Posterior cortical atrophy: a neuropsychological andneuroimaging study

This thesis investigates the neuroimaging and neuropsychological characteristics of Posterior Cortical Atrophy (PCA) which is most often caused by Alzheimer’s disease (AD) pathology. Posterior cortical atrophy describes a predominantly posterior pattern of atrophy and cognitive deficits. PCA has been poorly characterized and is likely to have been under-recognized. Using magnetic resonance imaging (MRI), patterns of cortical thickness were assessed in patients with pathologically-confirmed AD and different clinical presentations during life (including amnestic, visual and behavioural phenotypes). In addition to atrophy in the medial temporal lobe, tissue loss in posterior regions is indicative of AD pathology. Since medial temporal lobe atrophy is not specific to AD, posterior atrophy may aid distinction between AD and other dementias. Using easily-applied visual rating scales for medial temporal and posterior atrophy in patients with pathologically-confirmed AD and frontotemporal lobar degeneration (FTLD), it was shown that posterior atrophy ratings improve classification accuracy of AD from FTLD and controls. Cross-sectional and longitudinal image analysis techniques were used to characterize atrophy patterns in PCA compared with controls and typical amnestic AD. Whilst the cross-sectional analysis revealed differential patterns of tissue loss in these two groups, with PCA showing greatest atrophy in posterior parietal regions, and typical AD predominantly in medial temporal lobe regions, longitudinal results showed that at five years disease duration, both PCA and typical AD had global grey matter loss and cortical thinning compared with controls. The nature of visual deficits in PCA was assessed by administering detailed neuropsychological tests. The behavioural data showed that visual deficits were not uniformly affected in PCA, with considerable heterogeneity of visual impairments shown. Cortical thickness measures were used to assess atrophy patterns in PCA patients with predominant space versus object perception impairments, revealing overlap in cortical thinning patterns between these two PCA subgroups. In summary this thesis investigates the common and differential atrophy patterns of atypical AD presentations as well as the degree of heterogeneity of deficits which exist within the PCA presentation.