Spatial navigation testing discriminates two types of amnestic mild cognitive impairment

Laczó, Jan; Vlček, Kamil; Vyhnálek, Martin; Vajnerová, Olga; Ort, Michael; Holmerová, Iva; Tolar, Martin; Andel, Ross; Bojar, Martin; Hort, Jakub

doi:10.1016/j.bbr.2009.03.041

Cited by 131 publications

(131 citation statements)

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“…It is designed to separate 2 different modes of navigation, allocentric (independent of individual’s position, where distal cues are used for navigation) and egocentric (dependent on individual’s position, where start position is used for navigation) [21]. …”

Section: Methodsmentioning

confidence: 99%

Spatial Navigation and APOE in Amnestic Mild Cognitive Impairment

et al. 2010

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Background: The effect of APOE Ε4 allele (Ε4) on spatial navigation in amnestic mild cognitive impairment (aMCI) is unknown. Objective: Our purpose was to examine the characteristics of spatial navigation impairment in Ε4-positive (Ε4+) and Ε4-negative (Ε4–) aMCI subgroups. Methods: Blood samples were collected to determine the APOE genotype. A total of 34 aMCI patients were stratified into aMCI-Ε4– (n = 23) and aMCI-Ε4+ (n = 11) groups. Control (n = 28) and mild Alzheimer’s disease (AD; n = 16) groups were also used. We used a human analogue of the Morris water maze (enclosed arena 2.9 m in diameter) to examine body-centered (egocentric) and world-centered (allocentric) spatial navigation. Results: The aMCI-Ε4+ group performed poorer on spatial navigation than the aMCI-Ε4– group in both egocentric and allocentric tasks even though these 2 groups did not differ in global cognitive functioning or neuropsychological tests. The aMCI-Ε4+ and mild AD groups performed similarly on all Morris Water Maze tasks and were outperformed by the aMCI-Ε4– group, which also resembled the control group in performance on the egocentric tasks. The aMCI groups showed poor spatial navigation learning regardless of their Ε4 positivity. Conclusion: We found more profound deficits in spatial navigation in aMCI-Ε4+ relative to aMCI-Ε4– patients. The aMCI-Ε4+ group resembled the mild AD group in spatial navigation performance. Although the Ε4 genotype was indicative of spatial navigation performance, it was not indicative of the aMCI patients’ ability to learn the tasks. Spatial navigation testing represents a promising area with respect to identifying individuals at higher risk for AD among the heterogeneous MCI population.

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Section: Methodsmentioning

confidence: 99%

Spatial Navigation and APOE in Amnestic Mild Cognitive Impairment

et al. 2010

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“…Participants with depression were excluded. Patients were classified based on the clinical criteria and results of the neuropsychological tests [4] into the mild AD and aMCI groups. Patients in the mild AD group (n = 21; age 75.9 8 5.6 years; 81% female; education 12.3 8 3.3 years; MMSE score 23.1 8 3.7) met the DSM-IV-TR criteria for dementia and the NINCDS-ADRDA criteria for probable AD [6] .…”

Section: Subjectsmentioning

confidence: 99%

“…Previously [4] , we found that spatial navigation testing in the real-space Hidden Goal Task (HGT), a human analogue of the Morris Water Maze [5] , can identify patients with aMCI of the hippocampal type (HaMCI). The HaMCI patients had characteristically poorer performance on both spatial navigation accuracy and learning as compared to nonhippocampal aMCI (NHaMCI) patients across trials, and they resembled patients with mild AD in their performance.…”

Section: Introductionmentioning

confidence: 99%

From Morris Water Maze to Computer Tests in the Prediction of Alzheimer’s Disease

Laczó¹,

Andel²,

Vyhnálek³

et al. 2011

Neurodegener Dis

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Background: Spatial navigation performance in the Hidden Goal Task (HGT), a real-space human analogue of the Morris Water Maze, can identify amnestic mild cognitive impairment (aMCI) patients with memory impairment of the hippocampal type, a known indicator of incipient Alzheimer’s disease (AD). Objective: Contrast results from computer versus real-space versions of the HGT. Methods: A total of 42 aMCI patients were clinically and neuropsychologically classified into: (1) memory impairment of the hippocampal type – the hippocampal aMCI (HaMCI; n = 10) and (2) isolated retrieval impairment – the nonhippocampal aMCI (NHaMCI; n = 32). Results were compared to the control (n = 28) and AD (n = 21) groups. Results: The HaMCI group, although similar to the NHaMCI group with respect to overall cognitive impairment, performed poorer on the computer version of the HGT and yielded parallel results to the real-space version. The two versions were strongly correlated. Conclusions: Both versions of the HGT can reliably identify aMCI with pronounced memory impairment of the hippocampal type. The computer version of the HGT may be a useful, relatively inexpensive screening tool for early detection of individuals at a high risk of AD.

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“…Classic human tests rely more on memory tests that are based on short stories or visual image reproductions (5). Recently, the MWM has been reverse translated for use in humans, providing evi dence that patients with AD are impaired in twodimensional, real space, and virtual reality versions of the task (7)(8)(9)(10).…”

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Wet or dry: translatable “water mazes” for mice and humans

Higa¹,

Young²,

Geyer³

2016

Journal of Clinical Investigation

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C o m m e n t a r y4A disconnect between animal models and human AD patientsAlzheimer's disease (AD) is a devastating illness and the leading cause of dementia in older adults. As with other neurological disorders, the study of AD relies on ani mal models in conjunction with human studies to explore the pathogenesis of the disease and to develop treatments to slow or prevent disease progression. Thus far, treatments with agents such as acetylcho linesterase (AChE) inhibitors to alleviate the cognitive deficits associated with AD produce only modest cognitive improve ments that are neither permanent nor preventative of further decline (1, 2). To better predict the efficacy of therapeutic strategies, it is necessary to develop trans latable paradigms that reliably model cognitive impairment (and improvement) across species, as discussed for other diseases with cognitive deficits such as schizophrenia (3, 4). The pathogenesis and biological sig natures of AD are well established, and several mouse lines have been developed to mimic β amyloid plaque and tau neuro fibrillary tangle formation (5, 6). These models often exhibit cognitive deficits similar to those observed in patients at various stages of AD. Directly translat able comparisons are limited, however, because rodents are assessed with etho logically relevant tasks, while patients are tested using pen and paper.For rodents, the most commonly used test of spatial learning and memory is the Morris water maze (MWM). There are several versions of the MWM designed to assess various elements of spatial learning and memory, and several mouse models of AD exhibit impaired performance in the MWM. Classic human tests rely more on memory tests that are based on short stories or visual image reproductions (5). Recently, the MWM has been reverse translated for use in humans, providing evi dence that patients with AD are impaired in twodimensional, real space, and virtual reality versions of the task (7-10).Although performance in the MWM of both mice and humans relies on hippo campal integrity (7, 11), especially the right hippocampus for AD patients (12), the extent to which rodent MWM performance can predict and be compared with human performance was heretofore unknown. In this issue, Possin et al. (13) assessed the translatability of MWM findings by using comparable mouse and human MWM para digms and measures (Table 1 and Figure 1), enabling direct comparisons across species. Performance comparison of species-specific MWM paradigmsBoth mouse and human versions had three test stages: visible target training, hidden target learning, and a probe test. The human test took place in a virtual cir cular field that was navigable with a steer ing wheel. This methodology enabled firstperson exploration of the space to find a reward. Mice, however, had to navigate through water to find first the visible, then hidden escape platforms. The performance measures analyzed for the visible and hid den target stages were distance (mean proximity to the target), latency (percent age of ...

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Spatial navigation testing discriminates two types of amnestic mild cognitive impairment

Cited by 131 publications

References 48 publications

Spatial Navigation and APOE in Amnestic Mild Cognitive Impairment

Spatial Navigation and APOE in Amnestic Mild Cognitive Impairment

From Morris Water Maze to Computer Tests in the Prediction of Alzheimer’s Disease

Wet or dry: translatable “water mazes” for mice and humans

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