Temporal Order Memory Assessed during Spatiotemporal Navigation As a Behavioral Cognitive Marker for Differential Alzheimer's Disease Diagnosis

Pierre et Marie Curie Paris 6 University, Navigation, Memory and Aging Team, Equipe Navigation Memoire et Vieillissement team, UMR7102, CNRS, F75005 Paris, France.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 02/2012; 32(6):1942-52. DOI: 10.1523/JNEUROSCI.4556-11.2012
Source: PubMed


Episodic memory impairment is a hallmark for early diagnosis of Alzheimer's disease. Most actual tests used to diagnose Alzheimer's disease do not assess the spatiotemporal properties of episodic memory and lead to false-positive or -negative diagnosis. We used a newly developed, nonverbal navigation test for Human, based on the objective experimental testing of a spatiotemporal experience, to differentially Alzheimer's disease at the mild stage (N = 16 patients) from frontotemporal lobar degeneration (N = 11 patients) and normal aging (N = 24 subjects). Comparing navigation parameters and standard neuropsychological tests, temporal order memory appeared to have the highest predictive power for mild Alzheimer's disease diagnosis versus frontotemporal lobar degeneration and normal aging. This test was also nonredundant with classical neuropsychological tests. As a conclusion, our results suggest that temporal order memory tested in a spatial navigation task may provide a selective behavioral marker of Alzheimer's disease.

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    • "Successfulness in other spatial tasks is probably also connected to hippocampal function. Memory for temporal sequence of three body turns in a Starmaze was documented to activate left hippocampus (Igloi et al., 2010) and later shown to distinguish well between mild AD patients and controls (Bellassen et al., 2012). Memory for location of objects in space was several time consistently shown to be dependent on hippocampal function (Milner et al., 1997; Kessels et al., 2004; Stepankova et al., 2004) and reported to be deficient in patients suffering AD (Bucks and Willison, 1997; Brandt et al., 2005) and also in MCI patients, although to a lesser degree than in AD (Kessels et al., 2010). "
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    ABSTRACT: Although the memory impairment is a hallmark of Alzheimer's disease (AD), AD has also been characterized by spatial disorientation, which is present from its early stages. Spatial disorientation in AD manifests itself in getting lost in familiar and unfamiliar places and have been characterized more specifically using spatial navigation tests in both real space and virtual environments as an impairment in multiple spatial abilities, including allocentric and egocentric navigation strategies, visuo-spatial perception, or selection of relevant information for successful navigation. Patients suffering mild cognitive impairment (MCI), who are at a high risk of development of dementia, show impairment in a subset of these abilities, mainly connected with allocentric and egocentric processing. While spatial disorientation in typical AD patients probably reflects neurodegenerative changes in medial and posterior temporal, parietal, and frontal lobes, and retrosplenial cortex, the impairment of spatial navigation in MCI seem to be connected mainly with the medial temporal and also parietal brain changes. In this review, we will summarize the signs of brain disease in most MCI and AD patients showing in various tasks of spatial memory and navigation.
    Frontiers in Behavioral Neuroscience 03/2014; 8:89. DOI:10.3389/fnbeh.2014.00089 · 3.27 Impact Factor
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    • "Our results may have further clinical implications in light of a 2012 report that impaired temporal order memory may be a selective behavioral marker of Alzheimer disease (Bellassen et al, 2012). In coming years, these combined findings could have particular meaning for the growing number of people with HIV infection who are living into their 60s and beyond (High et al, 2012). "
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    ABSTRACT: To compare temporal order memory in older adults with and without human immunodeficiency virus (HIV) infection. The frontal and temporal lobes play a key role in temporal order memory for items in a sequence. HIV-associated episodic memory deficits correlate with damage to neocortical interneurons in the fronto-striato-thalamo-cortical pathway and with atypical activation of the medial temporal lobes. Therefore, temporal order memory may be sensitive to neuropathological changes in individuals with HIV. In this study, 50 HIV-seropositive individuals aged ≥ 50 years and 50 seronegative controls performed a computerized visuospatial temporal order memory task. During the sample phase of each trial, participants were shown circles presented 1 at a time in a random sequence at the end of each of the 8 arms of a radial maze. During the choice phase, they were shown the maze with a circle at the ends of 2 of the arms and asked which circle had appeared earlier than the other in the original sequence. Performance in both groups improved as a function of greater temporal separation between circle presentations. However, the HIV group had significantly worse memory impairment across all temporal separations, and the impairment was independently associated with clinical deficits in executive function and delayed retrospective memory. Our results extend prior findings that HIV is associated with deficits in strategic aspects of memory encoding and retrieval. The neural mechanisms warrant further research, as do potential impacts on everyday function, eg, adherence to antiretroviral drug regimens.
    Cognitive and behavioral neurology: official journal of the Society for Behavioral and Cognitive Neurology 12/2013; 26(4):171-80. DOI:10.1097/WNN.0000000000000013 · 0.95 Impact Factor
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    • "In this study, the patients, who made at least one error on the road, did not differ in neuropsychological tests from those with no errors on the road, but they had lower right MTL and posterior parietal cortex volumes that probably underlie spatial navigation deficit. Temporal order spatial memory was recently suggested as another cognitive marker of AD and aMCI (Bellassen et al., 2012). Remembering a sequence of three turns in a simple maze distinguished well between AD, healthy older subjects, and group of patients with frontotemporal lobe degeneration. "
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    ABSTRACT: Spatial navigation is a skill of determining and maintaining a trajectory from one place to another. Mild progressive decline of spatial navigation develops gradually during the course of physiological ageing. Nevertheless, severe spatial navigation deficit can be the first sign of incipient Alzheimer's disease (AD), occurring in the stage of mild cognitive impairment (MCI), preceding the development of a full blown dementia. Patients with amnestic MCI, especially those with the hippocampal type of amnestic syndrome, are at very high risk of AD. These patients present with the same pattern of spatial navigation impairment as do the patients with mild AD. Spatial navigation testing of elderly as well as computer tests developed for routine clinical use thus represents a possibility for further investigation of this cognitive domain, but most of all, an opportunity for making early diagnosis of AD.
    Frontiers in Aging Neuroscience 06/2012; 4:16. DOI:10.3389/fnagi.2012.00016 · 4.00 Impact Factor
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