Approaching objects cause confusion in patients with Alzheimer's disease regarding their direction of self-movement

Department of Neurology, University of Rochester Medical Centre, 601 Elmwood Avenue, Rochester, NY 14642-0673, USA.
Brain (Impact Factor: 9.2). 09/2010; 133(9):2690-701. DOI: 10.1093/brain/awq140
Source: PubMed


Navigation requires real-time heading estimation based-on self-movement cues from optic flow and object motion. We presented a simulated heading discrimination task to young, middle-aged and older adult, normal, control subjects and to patients with mild cognitive impairment or Alzheimer's disease. Age-related decline and neurodegenerative disease effects were evident on a battery of neuropsychological and visual motion psychophysical measures. All subject groups made more accurate heading judgements when using optic flow patterns than when using simulated movement past earth-fixed objects. When both optic flow and congruent object were presented together, heading judgements showed intermediate accuracy. In separate trials, we combined optic flow with non-congruent object motion, simulating an independently moving object. In the case of non-congruent objects, almost all of our subjects shifted their perceived self-movement to heading in the direction of the moving object. However, patients with Alzheimer's disease uniquely indicated that perceived self-movement was straight-ahead, in the direction of visual fixation. The tendency to be confused by objects that appear to move independently in the simulated visual scene corresponded to the difficulty patients with Alzheimer's disease encountered in real-world navigation through the hospital lobby (R(2) = 0.87). This was not the case in older normal controls (R(2) = 0.09). We conclude that perceptual factors limit safe, autonomous navigation in early Alzheimer's disease. In particular, the presence of independently moving objects in naturalistic environments limits the capacity of patients with Alzheimer's disease to judge their heading of self-movement.

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    • "In a series of studies, Duffy and colleagues investigated AD patients' perceptual capacity to process optic flow (Page and Duffy, 1999, 2003; Tetewsky and Duffy, 1999; O'Brien et al., 2001; Kavcic and Duffy, 2003; Mapstone et al., 2003, 2008; Monacelli et al., 2003; Duffy et al., 2004; Kavcic et al., 2006; Mapstone and Duffy, 2010). These studies demonstrated that visuospatial disorientation in AD is caused, not only by impairment in landmark orientation mechanisms due to hippocampal damage (Burgess et al., 2006; Laczó et al., 2009), but also by inability to utilize optic flow information. "
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    ABSTRACT: The present study explored whether the optic flow deficit in Alzheimer’s disease (AD) reported in the literature transfers to different types of optic flow, in particular, one that specifies collision impacts with upcoming surfaces, with a special focus on the effect of retinal eccentricity. Displays simulated observer movement over a ground plane toward obstacles lying in the observer’s path. Optical expansion was modulated by varying τ˙. The visual field was masked either centrally (peripheral vision) or peripherally (central vision) using masks ranging from 10° to 30° in diameter in steps of 10°. Participants were asked to indicate whether their approach would result in “collision” or “no collision” with the obstacles. Results showed that AD patients’ sensitivity to τ˙ was severely compromised, not only for central vision but also for peripheral vision, compared to age- and education-matched elderly controls. The results demonstrated that AD patients’ optic flow deficit is not limited to radial optic flow but includes also the optical pattern engendered by τ˙. Further deterioration in the capacity to extract τ˙ to determine potential collisions in conjunction with the inability to extract heading information from radial optic flow would exacerbate AD patients’ difficulties in navigation and visuospatial orientation.
    Full-text · Article · Nov 2015 · Frontiers in Aging Neuroscience
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    • "Observing a relationship between the function of the septohippocampal system and self-movement cue processing in rats provides a translational model to investigate the factors that contribute to wandering behavior observed during the progression of DAT. For example, recent work has demonstrated deficits in self-movement cue processing observed during the progression of DAT that was related to disruptions in spatial orientation (Tetewsky and Duffy 1999; Kavcic et al. 2006; Mapstone and Duffy 2010). The combination of selective lesion techniques and behavioral tasks that can dissociate the type of cues used to guide movement and mnemonic function provides the foundation necessary to model disruptions in spatial orientation associated with neurodegenerative disorders. "
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    ABSTRACT: Degeneration of the septohippocampal system is associated with the progression of Dementia of the Alzheimer's type (DAT). Impairments in mnemonic function and spatial orientation become more severe as DAT progresses. Although evidence supports a role for cholinergic function in these impairments, relatively few studies have examined the contribution of the septohippocampal GABAergic component to mnemonic function or spatial orientation. The current study uses the rat food-hoarding paradigm and water maze tasks to characterize the mnemonic and spatial impairments associated with infusing GAT1-Saporin into the medial septum/vertical limb of the diagonal band (MS/VDB). Although infusion of GAT1-Saporin significantly reduced parvalbumin-positive cells in the MS/VDB, no reductions in markers of cholinergic function were observed in the hippocampus. In general, performance was spared during spatial tasks that provided access to environmental cues. In contrast, GAT1-Saporin rats did not accurately carry the food pellet to the refuge during the dark probe. These observations are consistent with infusion of GAT1-Saporin into the MS/VDB resulting in spared mnemonic function and use of environmental cues; however, self-movement cue processing was compromised. This interpretation is consistent with a growing literature demonstrating a role for the septohippocampal system in self-movement cue processing.
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    • "The authors considered that the failure of cue integration was due to the loss of cortico-cortical connectivity in the parietal visual association cortex. Furthermore, neuropsychological studies reported impairments in visuospatial perception including the perception of OF and self-movement in patients with MCI [75] [76] [77]. Thus, a large number of studies show impairment in the higher level dorsal stream in AD and MCI. "
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    ABSTRACT: Visuospatial dysfunction including defects in motion perception in Alzheimer's disease (AD) and mild cognitive impairment (MCI) are clues to search for potential in vivo biomarkers. In this review, we focus on the clinical relevance of non-invasive neurophysiological findings in event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) to assess visual dysfunction in AD and MCI. We first summarize the current concept of the parallel visual pathways in primates and humans. Next, we outline the results of previous electrophysiological and fMRI studies on visual function in AD and MCI. Finally, we present the recent findings of our systematic ERP and fMRI approach to visual perception in AD and MCI. Our overview strongly indicates that visual impairments in patients with AD and MCI are mainly caused by dysfunction in higher-level parallel visual pathways. In particular, a deficit in ventro-dorsal stream function related to optic flow perception is responsible for the earliest and most prominent visual symptoms in MCI. Therefore, we conclude that ERP and fMRI measurements for visual perception can be used as in vivo biomarkers for early functional brain changes in MCI and AD patients.
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