Abstract
The basal forebrain degenerates in Alzheimer’s disease (AD) and this process is believed to contribute to the cognitive decline observed in AD patients. Impairment in spatial navigation is an early feature of the disease but whether basal forebrain dysfunction in AD is responsible for the impaired navigation skills of AD patients is not known. Our objective was to investigate the relationship between basal forebrain volume and performance in real space as well as computer-based navigation paradigms in an elderly cohort comprising cognitively normal controls, subjects with amnestic mild cognitive impairment and those with AD. We also tested whether basal forebrain volume could predict the participants’ ability to perform allocentric- vs. egocentric-based navigation tasks. The basal forebrain volume was calculated from 1.5 T magnetic resonance imaging (MRI) scans, and navigation skills were assessed using the human analog of the Morris water maze employing allocentric, egocentric, and mixed allo/egocentric real space as well as computerized tests. When considering the entire sample, we found that basal forebrain volume correlated with spatial accuracy in allocentric (cued) and mixed allo/egocentric navigation tasks but not the egocentric (uncued) task, demonstrating an important role of the basal forebrain in mediating cue-based spatial navigation capacity. Regression analysis revealed that, although hippocampal volume reflected navigation performance across the entire sample, basal forebrain volume contributed to mixed allo/egocentric navigation performance in the AD group, whereas hippocampal volume did not. This suggests that atrophy of the basal forebrain contributes to aspects of navigation impairment in AD that are independent of hippocampal atrophy.
Highlights
The basal forebrain, encompassing the septum, vertical and horizontal diagonal bands of Broca, and the nucleus basalis of Meynert, degenerates in Alzheimer’s disease (AD), and this process plays a role in the general cognitive decline observed in AD patients (Mufson, 2003; Schliebs and Arendt, 2006)
Group comparisons revealed that the mean whole (Figure 2A; p = 0.032), as well as the anterior (Figure 2B; p = 0.044), but not the posterior (Figure 2C) basal forebrain volumes were significantly reduced in amnestic mild cognitive impairment (aMCI) subjects compared to normal controls (NC)
In the current cohort of subjects basal forebrain volumes were not significantly reduced in the AD group compared to the NC group, atrophy of the basal forebrain, the anterior area, was found to be significantly correlated to real space allocentric navigation, as well as to mixed allo/egocentric navigation in real space and computer-based tasks
Summary
The basal forebrain, encompassing the septum, vertical and horizontal diagonal bands of Broca, and the nucleus basalis of Meynert, degenerates in Alzheimer’s disease (AD), and this process plays a role in the general cognitive decline observed in AD patients (Mufson, 2003; Schliebs and Arendt, 2006). The administration of donepezil, an acetylcholine esterase inhibitor that is used to treat cognitive dysfunction in patients diagnosed with mild AD by prolonging synaptic acetylcholine availability, has been shown to improve the allocentric navigation performance of patients in a human analog of the Morris water maze (hMWM; Hort et al, 2014), a commonly used spatial working memory task. Taken together, these studies suggest a role for basal forebrain function in allocentric navigation; the role of the basal forebrain in allocentric vs egocentric spatial navigation has never been studied in vivo in humans These studies suggest a role for basal forebrain function in allocentric navigation; the role of the basal forebrain in allocentric vs. egocentric spatial navigation has never been studied in vivo in humans
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