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Spatial cognition and the human navigation network in AD and MCI

From the Gladstone Institute of Neurological Disease (A.R.d.I., L.M.), Neuroscience Graduate Program (A.R.d.I., L.M.), and Memory and Aging Center (A.R.d.I., K.P.R., L.M., B.L.M., M.L.G.-T.), Department of Neurology, University of California, San Francisco, CA.

Address correspondence and reprint requests to Dr. Bruce Miller, UCSF Memory and Aging Center, 350 Parnassus Avenue, Suite 706, San Francisco, CA 94143-1207 bmiller{at}memory.ucsf.edu

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.

Supplemental data at www.neurology.org

Supported by the State of California (DHS 04-35516; 03-75271 DHS/ADP/ARCC), the National Institute on Aging (P50 AG03006, P01 AG019724), the National Institute of Neurological Disorders and Stroke (R01 NS050915), the John Douglas French Alzheimer’s Foundation, the McBean Foundation, the Sandler Foundation, the Larry Hillblom Foundation (grant 2002/2F), and the Koret Foundation (grant 99-0102).

Disclosure: The authors report no conflicts of interest.

Received December 6, 2006. Accepted in final form April 5, 2007.

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