Functional and Structural Brain Alterations in Patients with Posterior Cortical Atrophy (P5.189)

Objective. To assess white matter (WM) and functional connectivity alterations in patients with posterior cortical atrophy (PCA) compared to a population of healthy controls. Background. PCA is an atypical variant of Alzheimer’s disease characterized by an early age of onset, visuospatial impairment and occipital and posterior temporal-parietal atrophy. Up to date, the functional connectivity in these patients has been poorly investigated. Methods. Seven probable PCA patients (age-at-onset: 56±5 years; age-at-MRI: 61±5 years; disease duration: 4±2 years) and 21 healthy controls underwent T1-weighted, diffusion tensor (DT) and resting state functional (RS-fMRI) MRI. We assessed WM microstructure using a voxel-wise method and RS-fMRI data using a model free approach accounting for gray matter. Results. Compared with controls, PCA patients showed a distributed and symmetrical pattern of WM microstructural alterations in the corpus callosum, parahippocampal tracts, anterior and posterior cingulum, superior and inferior longitudinal fasciculi, and inferior fronto-occipital fasciculus. Compared with controls, PCA patients showed also decreased functional connectivity of: the bilateral calcarine gyrus, left cuneus and left middle and inferior occipital gyri within the visual-network; the right calcarine gyrus and precuneus, left superior and middle temporal gyri, left cuneus and lingual gyrus within the default-mode-network; the bilateral medial-superior frontal gyrus and right anterior cingulum within the fronto-striatal network; the left thalamus and hippocampus within the attentional-network; and the left superior temporal gyrus, supramarginal gyrus and paracentral lobule within the salience-network. Conclusions. This study shows that PCA is characterized by a pattern of WM damage which is more widely distributed than expected on the basis of cortical atrophy, and altered functional connectivity which extends beyond the visual and default-mode networks. Structural and functional abnormalities in the frontal and temporal circuits of PCA patients may suggest a progression of the disease from the posterior to the most anterior brain regions.