Abstract
BACKGROUND AND PURPOSE: To assess the neural substrates underlying topographical disorientation (TD) in patients affected by mild cognitive impairment (MCI), forty-one patients diagnosed with MCI and 24 healthy control individuals were recruited. METHODS: TD was assessed clinically in all participants. Neurological and neuropsychological evaluations and a volumetric-head magnetic resonance imaging scan were performed in each participant. Voxel-based morphometry was used to compare patterns of gray-matter atrophy between patients with and without TD, and a group of normal controls. RESULTS: We found TD in 17 out of the 41 MCI patients (41.4%). The functional abilities were significantly impaired in MCI patients with TD compared to in MCI patients without TD. Voxel-based morphometry analyses showed that the presence of TD in MCI patients is associated with loss of gray matter in the medial temporal regions, including the hippocampus and parahippocampal cortex, the fusiform gyrus, the inferior occipital gyrus, the amygdala, and the cerebellum. CONCLUSIONS: The findings found in this study represent the first evidence that the presence of TD in patients with MCI is associated with loss of gray matter in those brain regions that have been documented to be responsible for orientation in both neuropsychological and neuroimaging studies.