A JOURNAL OF NEUROLOGY
Approaching objects cause confusion in patients
with Alzheimer’s disease regarding their direction
Mark Mapstone1,2and Charles J. Duffy1,2,3,4,5
1 Department of Neurology, University of Rochester Medical Centre, Rochester, NY 14642, USA
2 Department of Brain and Cognitive Sciences, University of Rochester Medical Centre, Rochester, NY 14627, USA
3 Department of Neurobiology and Anatomy, University of Rochester Medical Centre, Rochester, NY 14642, USA
4 Department of Ophthalmology, University of Rochester Medical Centre, Rochester, NY 14642, USA
5 Centre for Visual Science, University of Rochester Medical Centre, Rochester, NY 14627, USA
Correspondence to: Charles J. Duffy,
Department of Neurology,
University of Rochester Medical Centre,
601 Elmwood Avenue,
Rochester, NY 14642-0673, USA
Navigation requires real-time heading estimation based-on self-movement cues from optic flow and object motion. We pre-
sented 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 (R2=0.87). This was not the case in older normal controls (R2=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.
Keywords: Alzheimer’s disease; mild cognitive impairment; visual cognition; cerebral cortex; cognitive neurology
Abbreviations: MCI = mild cognitive impairment
Self-movement perception relies on the integration and segrega-
tion of visual cues. Cues about a moving observer’s heading
direction are imbedded in the radial pattern of visual motion in
optic flow. The heading cues in optic flow are supplemented by
the relative visual movement of earth-fixed landmark objects,
which move in a manner that is congruent with the optic flow
doi:10.1093/brain/awq140Brain 2010: 133; 2690–2701 |
Received February 20, 2010. Revised April 7, 2010. Accepted April 28, 2010. Advance Access publication July 20, 2010
? The Author (2010). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
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field. In contrast, independently moving objects violate the radial
pattern of optic flow and provide robust cues for detecting threats
and following targets that are themselves moving through the
The human integration of visual cues regarding self-movement
is associated with the activation of posterior cortical areas by optic
flow and object motion stimuli (Aguirre and D’Esposito, 1997).
Functional imaging reveals selective activation by optic flow in
dorsal stream parietotemporal visual processing areas (Morrone
et al., 2000; Goossens et al., 2006) with object motion resulting
in selective activation in overlapping (Shulman et al., 1999) or
adjacent temporal areas (Epstein et al., 1999). The cortical path-
ology of Alzheimer’s disease has a great impact on these areas
(Arnold et al., 1991; Armstrong 1996), often as the first focal
pathology in patients particularly affected by visuospatial process-
ing impairments (Tang-Wai et al., 2004).
This posterior cortical localization of visual cue integration for
self-movement perception is consistent with the identification of
macaque monkey cortical neuronal populations specialized for
combining these optic flow and object motion cues (Logan and
Duffy, 2006). In these studies, recordings of medial superior tem-
poral neurons have shown a gating of object motion influence on
neuronal responses to optic flow; depending on whether the
object moves congruently with superimposed optic flow, or simu-
lating an independently-moving object, incongruently in violation
of the motion pattern in the optic flow. The effects of congruent
and incongruent object motion on optic flow-based heading esti-
mation have been well documented in psychophysical studies of
normal human subjects. These studies have reported disruptions of
heading estimation, particularly when the heading in optic flow
was obscured by an incongruently moving object (Royden and
Hildreth, 1999), in a manner that is consistent with computational
models of medial superior temporal neuronal function (Zemel and
Sejnowski, 1998; Royden, 2002).
We have previously shown that ageing and Alzheimer’s disease
are associated with successively greater difficulty in the perceptual
self-movement (Tetewsky and Duffy, 1999; O’Brien et al.,
2001). These deficits create a spectrum of impairment that has
several apparently independent components in the domains of
visual processing and cognitive function (O’Brien et al., 2001;
Mapstone et al., 2003). These impairments are linked to naviga-
tional disabilities (Cushman and Duffy, 2007) and neurophysio-
logical dysfunction (Kavcic et al., 2006). When integrated into
functional assessments of perceptual capacity for heading estima-
tion, they reveal an important distinction between older adults and
patients with Alzheimer’s disease (Mapstone et al., 2006): older
adults combine optic flow and congruent landmark object motion
cues to support accurate heading estimation, whereas in contrast,
patients with Alzheimer’s disease are confounded by congruent
object motion, such that it disrupts heading estimation from
optic flow. This may cause patients with Alzheimer’s disease to
have greater difficulty in self-movement heading estimation in
natural environments that include optic flow and landmark
In the current study, we superimposed non-congruent object
motion, simulating independently moving objects, on optic flow
stimuli. Our goal was to test the hypothesis that Alzheimer’s dis-
ease results in deficits of perceptual integration that might explain
further the behavioural limiting navigational impairment associated
with Alzheimer’s disease. We found evidence for a unique and
robust adverse impact of independently moving objects on head-
ing estimation in Alzheimer’s disease and that these factors greatly
contribute to navigational impairment in those patients.
Materials and methods
A total of 132 individuals participated in this study. Thirteen patients
with early Alzheimer’s disease and 20 patients with mild cognitive
impairment (MCI) were referred to the study by a dementia neurolo-
gist or psychiatrist affiliated with the clinical programs at the University
of Rochester Medical Centre. All patients with early Alzheimer’s dis-
ease met National Institute of Neurological and Communicative
Disorders and Stroke–Alzheimer’s Disease and Related Disorders
Association (NINCDS–ADRDA) criteria for probable Alzheimer’s dis-
ease (McKhann et al., 1984). All participants with MCI met criteria
for amnestic MCI (Petersen, 1996). Ninety-nine participants served as
normal control subjects. The normal control participants were divided
into three groups in order to examine the effects of ageing. Thirty-nine
older adult normal control subjects were between the ages of 60 and
84 years, 27 middle-aged normal control subjects were between the
ages of 40 and 59 years, and 33 younger adult normal control subjects
were between the ages of 20 and 39 years. The older normal control
group included volunteers from the community and many were
spouses or caregivers of participants with early Alzheimer’s disease
or MCI. The middle-aged normal control group were volunteers
from the community and employees of the University of Rochester
or Strong Memorial Hospital. The younger normal control group
were students or staff at the University of Rochester. All participants
were free from neurological and psychiatric illness with the exception
of Alzheimer’s disease in the early Alzheimer’s disease group and MCI
in the MCI group. Thirty percent of the early Alzheimer’s disease
group and 40% of the MCI group were female, while 50% were
female in the older normal control group, 70% were female in the
middle-aged normal control group and 51% were female in the
younger normal control group. All participants had corrected binocular
visual acuity of at least 20/40 and were free from ophthalmic illness.
All subjects in this study were native speakers of English. As defined,
the younger, middle-aged and older normal control groups differed in
age (P50.001), but the older normal controls, MCI and early
Alzheimer’s disease groups did not (P40.05) (Table 1). We previously
reported a separate set of experiments that included a subset of this
sample (Mapstone et al., 2006). All patients with early Alzheimer’s
disease, 30 older normal controls, 17 middle-aged normal controls
and 18 younger normal controls in the present study were part of
the previously published study. In the present study, we report on a
new experiment, add additional subjects in the three normal control
groups and include the new patient group of MCI subjects to examine
more closely perceptual changes that occur during the transition from
normal ageing to Alzheimer’s disease.
All testing was completed in the Visual Orientation Laboratory at the
University of Rochester Medical Centre in three, 1h sessions. The
Cue conflicts in aging and ADBrain 2010: 133; 2690–2701 |
The unique deficits seen in our patients with early Alzheimer’s
disease when confronted with incongruent object motion may re-
flect the combined breakdown of top-down attentional control of
sensory processing, superimposed on the vulnerability of the
(O’Brien et al., 2001; Mapstone et al., 2003). These findings
might also be interpreted as a loss of attentional control over
the allocation of visual processing capacity to competing stimuli,
as in dual-task interference (Pashler, 1993). Such an interpretation
may be consistent with the loss of attentional control in ageing as
a resultof impairedfrontal
(Greenwood, 2000; Mapstone et al., 2008).
cortical control mechanisms
Perception limits navigation in
We characterized our subject’s navigational capacities using a
real-world test battery, replicating our previous findings of succes-
sive impairment in ageing and Alzheimer’s disease (Monacelli et al.,
2003; Cushman et al., 2008). Multiple linear regression show a
significant, but small relationship between navigation and percep-
tual measures, and a much stronger relationship in patients with
early Alzheimer’s disease (Fig. 5). In both groups, the only signifi-
cant factors were the heading estimation errors seen with congruent
optic flow and object motion stimuli and with object motion alone.
The robust relationship between navigation and heading estima-
tion with object motion in patients with early Alzheimer’s disease
may reflect two factors. First, the salient characteristics of archi-
tectural environments, such as the hospital lobby used in our navi-
gational test battery, contain a large number of recognizable objects
that are fixed to the environment (e.g. structural features and fur-
nishings) forming congruent self-movement cues. Thus, navigation
through such an environment may depend on the processing of
those cues. Second, patients with early Alzheimer’s disease may
show more robust effects because of the large magnitude and
greater group variability of their object heading estimation errors.
Heading estimation errors with incongruent stimuli may not account
for a significant degree of variance in navigational performance be-
cause incongruent objects reflect independent object motion and
have little utility as navigational cues. We must be mindful that,
during independent ambulation, the mobility problems of many
older adults may obscure the relationships seen in this study.
The consistent conclusion of these studies is that patients with
early Alzheimer’s disease uniquely exhibit great difficulty in inter-
preting object motion as a heading estimation cue. This finding
contrasts with the graded impact of ageing and Alzheimer’s dis-
ease in the less naturalistic setting of two-alternative forced choice
left-right heading discrimination, especially in comparison. The sig-
nificance of these findings is highlighted by the context of the sub-
stantial, detrimental impact of Alzheimer’s disease on optic flow
heading discrimination. The combined effect of being unable to
process the radial motion patterns of optic flow (O’Brien et al.,
2001; Mapstone et al., 2008), and being unable to interpret
object motion as a heading cue, may account for devastating effects
of Alzheimer’s disease on navigation and visuospatial orientation
(Monacelli et al., 2003; Cushman et al., 2008).
This perspective differs from the more conventional view that
relates navigational impairment in Alzheimer’s disease to the dis-
ease’s impact on hippocampal mechanisms related to cognitive
mapping (Burgess et al., 2006; Laczo et al., 2009). Our findings
support a systems perspective on navigational impairment in
Alzheimer’s disease, recognizing a role for the hippocampus but
also the important role of a distributed cortical and sub-cortical
system for navigation (Duffy et al., 2010) including many foci of
pathology in Alzheimer’s disease (Brun and Gustafon 1976;
Rosenbaum et al., 2005).
We conclude that optic flow perceptual factors limit safe, au-
tonomous navigation in Alzheimer’s disease, particularly the cap-
acity to integrate the variety of potentially conflicting cues present
in naturalistic environments. Our work suggests that many
Alzheimer’s patients, even in the earliest stages of the disease,
may have difficulty judging their own heading especially in the
presence of an independently moving object. The results of this
study highlight the importance of early screening for visual percep-
tual impairments in elderly drivers, which will become important as
we face a projected increase in the prevalence of Alzheimer’s dis-
ease in the coming decades. Ultimately, we hope these findings
can help guide novel strategies designed to enhance the visual
environment and improve driving performance in the elderly.
The authors gratefully acknowledge the assistance of Mark
Abroms, David Logan, Teresa Steffenella and William Vaughn in
conducting these experiments.
NIA grants AG17596 and AG20647, NEI grant EY10287.
Conflict of interest: Dr Duffy is a principal of Cerebral Assessment
Systems, Inc. from which he received that portion of his regular
salary for time not devoted to this funded research.
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