Spatial navigation impairment is proportional to right hippocampal volume

Abstract

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...

The association of brain structure with gait velocity in older adults: a quantitative volumetric analysis of brain MRI

“…This might be explained by the critical role of right hippocampus in navigation [43]. It has been suggested that this role may be more prominent when cognitive impairment is present [44]. Alternatively, the right-sided findings may be due to asymmetric neurodegeneration and reorganization of neuronal motor pathways.…”

Egocentric and allocentric visuospatial working memory in premotor Huntington's disease: A double dissociation with caudate and hippocampal volumes

“…For example, transgenic mice expressing human amyloid precursor protein and patients with mild cognitive impairment with the predicted pathology of Alzheimer’s disease show similar impairments on analogous versions of an allocentric Morris Maze (Possin et al, 2016). Performance on an allocentric Morris Maze correlates with right hippocampal volumes in patients with amnestic mild cognitive impairment or Alzheimer’s disease (Nedelska et al, 2012) and with the size of CA1 hippocampal lesions in acute transient global amnesia (Bartsch et al, 2010). In functional neuroimaging studies, the medial temporal lobe activates in relationship to the spatial layout of virtual environments (Aguirre et al, 1996; Maguire et al, 1998; Mellet et al, 2000).…”

Effect of Donepezil in Alzheimer Disease Can Be Measured by a Computerized Human Analog of the Morris Water Maze

“…A subsequent study reported that the genetic risk factor for late-onset AD - apolipoprotein E e4 allele, which is frequently analyzed in clinical trials - further exacerbated spatial navigation impairment in aMCI patients [8]. The most recent study revealed that the right hippocampus was responsible for allocentric navigation impairment in prodromal AD [9], especially in subjects with cognitive impairment.…”