Spatial cognition and the human navigation network in AD and MCI

BACKGROUND: The mechanisms underlying navigation impairments in Alzheimer disease (AD) are unknown. We characterized navigation in AD and mild cognitive impairment (MCI) to test the hypothesis that navigation disability reflects selective impairments in spatial cognition and relates to atrophy of specific brain regions. METHODS: We compared 13 mild AD and 21 MCI patients with 24 controls on a route-learning task that engaged various spatial processes. Using structural MRI and optimized voxel-based morphometry, we also investigated the neural correlates of spatial abilities in a subset of subjects (10 AD, 12 MCI, 21 controls). RESULTS: AD and MCI patients recognized landmarks as effectively as controls, but could not find their locations on maps or recall the order in which they were encountered. Half of AD and one-quarter of MCI patients got lost on the route, compared with less than 10% of controls. Regardless of diagnosis, patients who got lost had lower right posterior hippocampal and parietal volumes than patients and controls who did not get lost. The ability to identify locations on a map correlated with right posterior hippocampal and parietal volumes, whereas order memory scores correlated with bilateral inferior frontal volumes. CONCLUSIONS: The navigation disability in Alzheimer disease and mild cognitive impairment (MCI) involves a selective impairment of spatial cognition and is associated with atrophy of the right-lateralized navigation network. Extensive spatial impairments in MCI suggest that navigation tests may provide early markers of cognitive and neural damage.