A unified brain system of orientation and its disruption in Alzheimer’s disease

OBJECTIVE: To investigate whether a unified brain system manages one’s orientation to different places, events and people in one’s environment, and test the hypothesis that failure of this system (disorientation) is an early sign of Alzheimer’s disease (AD). METHODS: A total of 46 participants (patients along the AD continuum and cognitively normal control subjects) were tested in a personalized, ecologically valid task of orientation relating to the participant’s own world in space, time and person under high–density electroencephalography. As a first step, we used evoked potential mapping to search for brain topography correlated with participants’ performance in orientating themselves to different places (space), events (time) and people (person) (Experiment 1). We then compared behavioral and electrophysiological changes in patients along the AD continuum (Experiment 2). RESULTS: We identified a specific brain topography (“orientation map”) that was active for orientation in space, time and person in correlation to participants’ performance. Both performance and the map’s strength gradually decreased from health to mild cognitive impairment (MCI) and from MCI to AD. Another map, immediately preceding the orientation map, showed the longest activity in patients with MCI, significantly more than both patients with AD and cognitively normal controls. INTERPRETATION: Our findings demonstrate that the same brain topography accounts for orientation in the different domains of space, time and person and provide a nexus between deterioration in patients’ orientation with the aggravation of Alzheimer’s disease.