Neuroimaging associations with spatial navigation impairment in Alzheimer’s disease continuum: A narrative review

Abstract

Identifying individuals with incipient Alzheimer’s disease (AD) are critical for early and targeted intervention before the dementia develops as AD progresses. Recently, emerging data have suggested that spatial navigation and neuroimaging could be utilized to identify individuals with prodromal AD. Compared to episodic memory, spatial navigation has fewer cultural and educational discrepancies and could serve as a promising marker for diagnosis and outcome measures in multicenter longitudinal studies with large cohorts. Furthermore, neuroimaging studies have contributed to our understanding of the structural and functional neural basis underlying spatial navigation and provided sensitive and non-invasive neuroimaging markers. The current review summarizes neuroimaging associations with spatial navigation impairment in the AD continuum, their potential pathophysiological mechanisms, and nonpharmacological interventions for spatial navigation impairments. We highlight the promising role of spatial navigation in the early identification of the preclinical and prodromal patients with potential risk of developing AD dementia. Multicenter large-scale longitudinal studies on patients across the AD continuum coupled with a standardized routine assessment of spatial navigation abilities in clinical settings are needed. This review may have implications for clinical practice and future research directions.

Geospatial environmental complexity, spatial brain volume, and spatial behavior across the Alzheimer's disease spectrum

“…As shown from the structural model, the isthmus cingulate and the posterior cingulate contributed the least to the allocentric spatial navigation construct relative to the other regions. This may be reflected by their distinct roles in the spatial navigation framework, as they are more prominently involved in mediating the conversion between allocentric and egocentric spatial navigation strategies 38 . Although the neural circuitry involving the retrosplenial cortex in spatial navigation transformation is still not fully understood, recent theoretical models of egocentric to allocentric transformation suggest sensory inputs from the retrosplenial cortex and the postrhinal cortex travel to grid cells located in the dorsomedial entorhinal cortex, which is then projected onto the place cells in the hippocampus 53,54 .…”

“…Utilization of hippocampal subregions may result in the development of a robust measurement model for the allocentric‐egocentric transformation construct. Likewise, inclusion of regions such as the caudate nucleus, retrosplenial cortex, anterior thalamus, and postrhinal cortex may provide more robust constructs for the allocentric and egocentric regions 38,55 …”

“…Likewise, inclusion of regions such as the caudate nucleus, retrosplenial cortex, anterior thalamus, and postrhinal cortex may provide more robust constructs for the allocentric and egocentric regions. 38,55 Cumulatively, previous spatial navigation studies suggested that age is negatively associated with spatial performance, with several studies associating lower volumes in the medial temporal lobe with impaired spatial navigation and processing. [56][57][58] Egocentric navigation skills are more preserved than allocentric navigation in older adults, but are still vulnerable to age-related changes.…”

“…In total, [N GM = 36] gray matter regions were available for assessment. The following regions were selected as regions of interest for their association with egocentric and allocentric spatial navigation: hippocampus, entorhinal cortex, parahippocampal gyrus, superior parietal lobule, inferior parietal lobule, precuneus, isthmus cingulate gyrus, and posterior cingulate gyrus 37,38 . The inferior parietal volume was calculated as the average of the supramarginal and the inferior parietal (i.e., angular gyrus) regions to better reflect the anatomical structures.…”

“…The following regions were selected as regions of interest for their association with egocentric and allocentric spatial navigation: hippocampus, entorhinal cortex, parahippocampal gyrus, superior parietal lobule, inferior parietal lobule, precuneus, isthmus cingulate gyrus, and posterior cingulate gyrus. 37 , 38 The inferior parietal volume was calculated as the average of the supramarginal and the inferior parietal (i.e., angular gyrus) regions to better reflect the anatomical structures. All gray matter volumes were adjusted for body size differences via analysis of covariance approach: Volume adj = Volume i − b × (ICV i − mean ICV), where for each participant i , b is the slope of regression of an ROI volume on intracranial volume (ICV) and mean ICV is the sample mean of ICV.…”