Differences in spatial navigation among patients with various neurodegenerative dementias

Editor's Notes

• #1: Ladies and gentlemen, good afternoon. It is a great pleasure for me to be given an opportunity to present the results of our preliminary study aiming to describe differences in spatial orientation among the most common types of neurodegenerative dementias.
• #2: Here are my disclosures – I have consulted several compaines and between 6/2012 and 4/2014 I holded a stocks of Polyhymnia-TS.
• #3: In patients with dementia, impairment of multiple cognitive functions leads to gradual deterioration of self-sufficiency. Spatial disorientation may also contribute to deterioration of self-sufficiency, because patients are limited in travelling or driving a car and so on. Orientation in space called navigation is impaired in most of the patients with dementia, in the beginning in unfamiliar environments and also in complex environments (for example in large department stores) and later on in familiar environment as well. Spatial navigation impairment is intensively studied and well described in patients with Alzheimer‘s disease, but is less studied in other types of dementia (although we know, that for example impairment of visuo-spatial function and episodes of desorientation are common features of patients with dementia with Lewy bodies).
• #4: According to the way how we use information from the environment to find the place where we go spatial navigation is divided into three basic strategies, which depend on different brain regions: First, cued navigation is the most simple navigation strategy, where a close orientation cue attached to the place where we go is used to find our destination. This navigation strategy depends on the striatum and intact higher visual perception (which depends on the occipital and partially on the parietal lobe). Second, egocentric navigation is a strategy, where we use a position of our body to find our final destination and we use the information about distance and direction from the place where we are to the place where we go. We do not use here any orientation cues. This navigation strategy depends on the parietal cortex. Third, allocentric navigation is the most complex navigation strategy, where we use mutual spatial relationships between our destination and distant orientation cues. We are able to find the place where we go regardless of the current position of our body. This navigation strategy depends on the hippocampus.
• #5: These three navigation strategies have not yet been directly compared in patients with dementia. The objective of the study was to compare differences in spatial navigation performance among patients with three most common types of neurodegenerative dementias — Alzheimer’s disease, frontotemporal lobar degeneration, and dementia with Lewy bodies
• #6: In this cross sectional study we recruited 61 patients with mild AD, 8 patients with DLB and 9 patients with FTLD. Of these 9 FTLD patients were 5 with FTD behavioral variant and 4 with primary progressive afasia, 3 of them with semantic and 1 with non-fluent variant. The subjects underwent a clinical and laboratory evaluation, MRI brain scan with subsequent automated volumetry, detailed neuropsychological examination and spatial navigation testing in the real-space human analogue of the Morris Water Maze.
• #7: The real-space human analogue of the MWM is a circular arena approximately 3 m in diameter and 3 m high, where the task was to locate an invisible goal on the arena‘s floor using a starting position or a orientation cue on the wall. The subjects moved to the goal with a long pole indicating their position.
• #8: The real-space human analogue of the Morris Water Maze allows to measure separately performance in each of the three spatial navigation components––cued navigation (using a close orientation cue), egocentric navigation (using a position of the body at the starting position with no orientation cue provided) and allocentric navigation (using a distant orientation cue). There were 4 trials for each spatial navigation component. In the cued and allocentic tests the subjects started each trial from the different starting position unlike the egocentric test, where the subjects started each trial from the same starting position. The testing was preceded by training to ensure that the subjects were familiar with the task.
• #9: The groups were similar in demographic characteristics with exception for age, where the FTLD group was younger than the other two groups.
• #10: With the exception of verbal memory the groups were different in all other cognitive functions (language functions approached significance), mainly because the FTLD group was better than other two groups with exception of the verbal fluency, where the FTLD group had the worst scores.
• #11: In the main analysis of spatial navigation performance we used the one-way analysis of variance, which showed differences among the groups. Specifically, in the cued navigation test, the FTLD group performed better than the AD (p=.030) and DLB (p=.006) groups. Further, in the egocentric navigation test, the DLB group had worse scores than AD (p=.012) and FTLD (p=.012) groups. Finally, in the allocentric navigation test there were no significant differences among the groups (p = 0.069).
• #12: Analyzing results from the MRI brain volumety we found that the groups were different in thickness of the parietal cortex, especially the AD and DLB groups had more pronounced thinning of precuneal area compared to the FTLD group. Further the DLB group had more pronounced thinning of the supramarginal gyrus compared to the FTLD group. Finally, we found a strong correlation between egocentric navigation and thicknesses of posterior parietal areas.
• #13: On the other hand, the groups did not differ in hippocampal volumes adjusted for head size.
• #14: Overall our results showed the differences in cued and egocentric navigation strategies among patients with three most common types of neurodegenerative dementias, where spatial navigation impairment may be least pronounced in FTLD and most pronounced in DLB patients. These differences in spatial navigation may be partially caused by different atrophy of specific brain structures. (We are fully aware of limitations of this preliminary study, especially of the small sample size in non AD groups, which is caused by the low prevalence of FTLD and DLB in our country. But still despite this limitation we have demonstrated above-mentioned specific differences in spatial navigation among the individuals with dementia. We are recruiting more patients to confirm these results on a larger sample.)
• #15: In conclusion, our results indicate that spatial navigation testing may provide additional information in the differential diagnosis of neurodegenerative dementias. Spatial navigation in patients with AD, FTLD and DLB can be reliably measured with the real-space human analogue of the Morris Water Maze, which may mimic navigation in the real world.
• #16: Finally I would like to thank my colleagues and all patients from the Czech Brain Aging Study who patricipated at this study and I am prepared to answer your questions. Thank you for your attention.