Human Analogue of the Morris Water Maze for Testing Subjects at Risk of Alzheimer's Disease

Department of Neurology, Charles University, Prague, Czech Republic.
Neurodegenerative Diseases (Impact Factor: 3.51). 03/2010; 7(1-3):148-52. DOI: 10.1159/000289226
Source: PubMed


Patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) have difficulties with spatial orientation. Objective: To test hypothesis that spatial navigation is impaired early in MCI patients representing the presymptomatic stage of AD.
We tested patients with probable AD (n = 21), MCI, further classified according to Petersen's criteria as amnestic MCI (aMCI) single domain (n = 11), aMCI multiple domain (n = 31), or nonamnestic MCI (n = 7). The aMCI group was also stratified using cued recall according to Dubois' criteria into memory impairment of the hippocampal type (n = 10) and isolated memory retrieval impairment-nonhippocampal (n = 32) and also according to ApoE4 status into E4+ (n = 12) and E4- (n = 30). These patients and controls (n = 28) were tested in the human variant of the Morris water maze. Depending on the subtest, the subjects could use the egocentric or allocentric (hippocampus-dependent) navigation.
The AD and aMCI multiple domain groups were impaired in all subtests. The aMCI single domain group was impaired in allocentric subtests. The hippocampal MCI group performed poorer than the nonhippocampal MCI group and similarly to the AD group. The ApoE4+ group was as bad as the AD group when compared with the E4- group.
aMCI subjects represent a very heterogeneous population, and spatial memory or cued recall examination can add more value to aMCI classification. ApoE4+ patients are more impaired than ApoE4- patients.

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Available from: Ross Andel, Aug 08, 2014
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    • "Hippocampal atrophy is well established in aMCI (Shi, Liu, Zhou, Yu, & Jiang, 2009; Yang et al., 2012), making tests that are sensitive to hippocampal damage/dysfunction appropriate for investigation, and a number of behavioral studies have investigated navigation performance in these patients. Work with a real-world navigation task based on the Morris Water Maze has shown that aMCI patients can be impaired, especially when an allocentric strategy is required (Hort et al., 2007; Laczó et al., 2010, 2009). When using navigation tasks in a functional imaging setting, the use of virtual reality tasks is critical. "
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    ABSTRACT: Spatial navigation requires a well-established network of brain regions, including the hippocampus, caudate nucleus, and retrosplenial cortex. Amnestic Mild Cognitive Impairment (aMCI) is a condition with predominantly memory impairment, conferring a high predictive risk factor for dementia. aMCI is associated with hippocampal atrophy and subtle deficits in spatial navigation. We present the first use of a functional Magnetic Resonance Imaging (fMRI) navigation task in aMCI, using a virtual reality analog of the Radial Arm Maze. Compared with controls, aMCI patients showed reduced activity in the hippocampus bilaterally, retrosplenial cortex, and left dorsolateral prefrontal cortex. Reduced activation in key areas for successful navigation, as well as additional regions, was found alongside relatively normal task performance. Results also revealed increased activity in the right dorsolateral prefrontal cortex in aMCI patients, which may reflect compensation for reduced activations elsewhere. These data support suggestions that fMRI spatial navigation tasks may be useful for staging of progression in MCI.
    Aging Neuropsychology and Cognition 08/2015; DOI:10.1080/13825585.2015.1073218 · 1.07 Impact Factor
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    • "Several real space human MWM analogs have been developed to test the human spatial navigation, mostly in dry circular arenas (Overman et al., 1996; Skolimowska et al., 2011). A real analog of the MWM has also been developed in our laboratory as an apparatus named the “Blue Velvet Arena (BVA)” (Stepankova et al., 1999; Laczo et al., 2010; see Figure 1B). The development of virtual environments (VE) provided a significant methodological advance, allowing the detailed recording of the subject's behavior, along with easy handling and presentation of stimuli. "
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    ABSTRACT: Objectives: Cognitive deficit is considered to be a characteristic feature of schizophrenia disorder. A similar cognitive dysfunction was demonstrated in animal models of schizophrenia. However, the poor comparability of methods used to assess cognition in animals and humans could be responsible for low predictive validity of current animal models. In order to assess spatial abilities in schizophrenia and compare our results with the data obtained in animal models, we designed a virtual analog of the Morris water maze (MWM), the virtual Four Goals Navigation (vFGN) task. Methods: Twenty-nine patients after the first psychotic episode with schizophrenia symptoms and a matched group of healthy volunteers performed the vFGN task. They were required to find and remember four hidden goal positions in an enclosed virtual arena. The task consisted of two parts. The Reference memory (RM) session with a stable goal position was designed to test spatial learning. The Delayed-matching-to-place (DMP) session presented a modified working memory protocol designed to test the ability to remember a sequence of three hidden goal positions. Results: Data obtained in the RM session show impaired spatial learning in schizophrenia patients compared to the healthy controls in pointing and navigation accuracy. The DMP session showed impaired spatial memory in schizophrenia during the recall of spatial sequence and a similar deficit in spatial bias in the probe trials. The pointing accuracy and the quadrant preference showed higher sensitivity toward the cognitive deficit than the navigation accuracy. Direct navigation to the goal was affected by sex and age of the tested subjects. The age affected spatial performance only in healthy controls. Conclusions: Despite some limitations of the study, our results correspond well with the previous studies in animal models of schizophrenia and support the decline of spatial cognition in schizophrenia, indicating the usefulness of the vFGN task in comparative research.
    Frontiers in Behavioral Neuroscience 04/2014; 8. DOI:10.3389/fnbeh.2014.00157 · 3.27 Impact Factor
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    • "The participants were tested in the real-space version of the hMWM that was located in the navigation setting called the Blue Velvet Arena – a fully enclosed cylindrical arena 2.8 m in diameter surrounded by a 2.9 m high dark blue velvet curtain (Figure 1A). The design of the Blue Velvet Arena and the real-space testing procedure were described in detail elsewhere (Laczó et al., 2009; Laczó et al., 2010). The aim was to locate the invisible goal in three different subtasks using the start position or two distal orientation cues, respectively (Figure 1B). "
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    ABSTRACT: Older age is associated with changes in the brain, including the medial temporal lobe, which may result in mild spatial navigation deficits, especially in allocentric navigation. The aim of the study was to characterize the profile of real-space allocentric (world-centered, hippocampus dependent) and egocentric (body-centered, parietal lobe dependent) navigation and learning in young vs. older adults, and to assess a possible influence of gender. We recruited healthy participants without cognitive deficits on standard neuropsychological testing, white matter lesions or pronounced hippocampal atrophy: 24 young participants (18-26 years old) and 44 older participants stratified as participants 60-70 years old (n=24) and participants 71-84 years old (n=20). All underwent spatial navigation testing in the real-space human analog of the Morris Water Maze, which has the advantage of assessing separately allocentric and egocentric navigation and learning. Of the 8 consecutive trials, trials 2-8 were used to reduce bias by a rebound effect (more dramatic changes in performance between trials 1 and 2 relative to subsequent trials). The participants who were 71-84 years old (p< .001), but not those 60-70 years old, showed deficit in allocentric navigation compared to the young participants. There were no differences in egocentric navigation. All three groups showed spatial learning effect (p´s ≤.01). There were no gender differences in spatial navigation and learning. The linear regression limited to older participants showed linear (β=0.30, p=.045) and quadratic (β=0.30, p=.046) effect of age on allocentric navigation. There was no effect of age on egocentric navigation. These results demonstrate that navigation deficits in older age may be limited to allocentric navigation, whereas egocentric navigation and learning may remain preserved. This specific pattern of spatial navigation impairment may help differentiate normal aging from prodromal Alzheimer’s disease.
    Frontiers in Aging Neuroscience 12/2013; 5:94. DOI:10.3389/fnagi.2013.00094 · 4.00 Impact Factor
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