Real-space navigation testing differentiates between amyloid-positive and -negative aMCI


To distinguish between patients with amyloid-positive (A+) and -negative (A–) amnestic mild cognitive impairment (aMCI) by simultaneously investigating navigation performance, visual exploration behavior, and brain activations during a real-space navigation paradigm.


Twenty-one patients with aMCI were grouped into A+ (n = 11) and A– cases by amyloid-PET imaging and amyloid CSF levels and compared to 15 healthy controls. Neuropsychological deficits were quantified by use of the Consortium to Establish a Registry for Alzheimer’s Disease–plus cognitive battery. All participants performed a navigation task in which they had to find items in a realistic spatial environment and had to apply egocentric and allocentric route planning strategies. 18F-fluorodeoxyglucose was injected at the start to detect navigation-induced brain activations. Subjects wore a gaze-controlled, head-fixed camera that recorded their visual exploration behavior.


A+ patients performed worse during egocentric and allocentric navigation compared to A– patients and controls (p < 0.001). Both aMCI subgroups used fewer shortcuts, moved more slowly, and stayed longer at crossings. Word-list learning, figural learning, and Trail-Making tests did not differ in the A+ and A– subgroups. A+ patients showed a reduced activation of the right hippocampus, retrosplenial, and parietal cortex during navigation compared to A– patients (p < 0.005).


A+ patients with aMCI perform worse than A– patients with aMCI in egocentric and allocentric route planning because of a more widespread impairment of their cerebral navigation network. Navigation testing in real space is a promising approach to identify patients with aMCI with underlying Alzheimer pathology.

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