Patients with Alzheimer's disease (AD) frequently have difficulties with spatial orientation in their day-to-day life. Although AD is typically preceded by amnestic mild cognitive impairment (MCI), spatial navigation has not yet been studied in MCI. Sixty-five patients were divided into five groups: probable AD (n ؍ 21); MCI, further classified as amnestic MCI single domain (n ؍ 11); amnestic MCI multiple domain (n ؍ 18), or nonamnestic MCI (n ؍ 7), and subjective memory complaints (n ؍ 8). These patients, together with a group of healthy control subjects (n ؍ 26), were tested by using a four-subtests task that required them to locate an invisible goal inside a circular arena. Each subtest began with an overhead view of the arena showed on a computer monitor. This was followed by a real navigation inside of the actual space, an enclosed arena 2.9 m in diameter. Depending on the subtest, the subjects could use the starting position and/or cues on the wall for navigation. The subtests thus were focused on allocentric and egocentric navigation. The AD group and amnestic MCI multipledomain group were impaired in all subtests. The amnestic MCI single-domain group was impaired significantly in subtests focused on allocentric orientation and at the beginning of the real space egocentric subtest, suggesting impaired memory for allocentric and real space configurations. Our results suggest that spatial navigation impairment occurs early in the development of AD and can be used for monitoring of the disease progression or for evaluation of presymptomiatic AD.allocentric navigation ͉ Alzheimer's disease ͉ egocentric navigation ͉ spatial memory ͉ biomarker
Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (β = −0.62, P < 0.001) and virtual (β = −0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P ≤ 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present.P ersons with Alzheimer's disease (AD) (1, 2) and with amnestic mild cognitive impairment (MCI) (3), who are known to be at higher risk for developing AD, experience difficulties with spatial navigation. Based on animal research, two basic navigation types were distinguished (4). Egocentric navigation is route or body centered and is dependent mainly on parietal cortices and caudate nucleus (4-8). The more flexible and complex allocentric type is world centered and it is dependent mainly on the hippocampus (5, 9). In humans, medial temporal lobe function is highly lateralized with the right hippocampus predominantly associated with spatial navigation and topographical memory (10). Recent research has underscored the importance of the hippocampus for spatial navigation in cognitively impaired subjects (11,12). For example, a case study of a patient with early AD (13) reported a distinct navigation deficit indicative of hippocampal atrophy. However, structural background of the allocentric navigation impairment has not yet been entirely elucidated, particularly in the real-space environment.The navigation disability in AD and MCI patients has been found to involve selective impairment of spatial cognition as...
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