The world's population is aging at an unprecedented rate, because the number of people
aged over 60 will rise from 784 million in 2011 to 2 billion by 2050. Such a dramatic
increase has made age-related cognitive decline and Alzheimer's disease (AD) a pressing
social and health concern. Work described in this volume considers scientific efforts
to understand the neural mechanisms of age-related changes in spatial navigation,
both in humans and non-human animal models. A central theme in these papers is that
damage to structures of the medial temporal lobe, including the hippocampus, contributes
to the difficulties in spatial memory found in aging and AD.
Tanila (2012) describes the use of the Morris Water Maze (MWM) task as a tool for
demonstrating memory impairments in mouse models of AD. Tanila (2012) points out important
challenges in working with mice compared to rats—the former are prone to hypothermia,
and exhibit strain differences in learning capacity. Strikingly, an impairment on
the swim task is seen in all established models of AD in mice, though its relationship
to the onset of amyloid plaque deposition or tau aggregation varies.
In the MWM, Yau and Seckl (2012) note that older rats with impaired performance have
higher corticosterone levels than those who are unimpaired. Higher corticosterone
levels shift the balance between mineralcorticoid- and glucocorticoid-receptor activation,
and are associated with decreases in long-term potentiation and memory. Yau and Seckl
(2012) review findings which show that reduction of an enzyme that increases glucocorticoids
results in improved spatial memory in aged rodents.
Holden and Gilbert (2012) review studies which show that pattern separation abilities
are impaired in older humans, monkeys, and rodents. Such a capacity likely relies
on the hippocampus, and in particular the dentate gyrus/CA3 cell regions. They hypothesize
that impaired pattern separation may result in impaired episodic memory in aging.
Penner and Mizumori (2012) also relate the pattern separation function of the hippocampus
in terms of the recognition of contexts. Their proposal is that the hippocampus produces
an error signal when a context is unexpected, and this ultimately drives dopaminergic
neurons in the ventral tegmental area. Aging affects this circuit by altering hippocampal
representations of context, mesolimbic-ventral striatum interactions, and the dopaminergic
Turning to humans, Adamo et al. (2012) investigated how aging affects path integration,
a key navigational process. Both task complexity and the sources of information available
to participants (i.e., visual vs. vestibular) had a substantial impact on the results.
These findings have important methodological implications, because studies on spatial
navigation are often confined to one sensory modality and do not systematically manipulate
Several studies demonstrate deficits in allocentric processing in healthy older adults.
Rosenbaum et al. (2012) showed that memory for the layout of long familiar Toronto
landmarks did not differ dramatically between young and older participants, but the
latter made many more errors in learning a new route in a hospital. These results
support a model where episodic-like representations of spatial information (hippocampus
dependent) give rise to more schematic (less detailed, but hippocampus independent)
representations with repeated experience.
Using virtual environment (VE) technology, Yamamoto and DeGirolamo (2012) found that
older participants had difficulties reconstructing the layouts of landmarks encountered
in a virtual city. Interestingly, performance was not impaired when they experienced
the environments from a bird's eye perspective. These results suggest that spatial
learning through exploratory navigation may be particularly vulnerable to adverse
effects of aging, whereas elderly adults may be able to maintain their map reading
skills relatively well.
Wiener et al. (2012) had participants learn a route through a VE that contained multiple
intersections. Compared to young controls, older adults had greater problems during
route retracing than during route repetition. While route repetition can be solved
with egocentric response or route strategies, successfully retracing a route requires
allocentric processing. These age-related deficits in route retracing are discussed
in the context of a potential shift from allocentric to egocentric navigation strategies
as a consequence of age-related hippocampal degeneration.
A bias toward egocentric response strategies with increasing age was also observed
by Bohbot et al. (2012). A virtual 8-arm radial maze served to assess spontaneous
navigation strategies, i.e., hippocampal-dependent spatial strategies vs. caudate
nucleus-dependent response strategies. Results showed that from childhood to old age,
the spontaneous use of egocentric response strategies increased substantially. In
a related study, Konishi and Bohbot (2013) showed that spontaneous spatial memory
strategies positively correlated with gray matter density in the hippocampus of older
participants. The combined results from both studies indicate that people who prefer
to use spatial memory strategies in their everyday lives may have increased gray matter
in the hippocampus and enhance the probability of healthy aging.
Beyond the hippocampus, aging also affects the integrity of a larger network of brain
structures, including prefrontal cortex. Harris et al. (2012) found that older humans
were impaired at switching from a route strategy to a place strategy on a virtual
plus maze task. Interestingly, this did not reflect a general difficulty in switching
between spatial strategies, as the switch from a place strategy to a route strategy
was not impaired. This may imply that interactions between the prefrontal cortex and
the hippocampus are affected with advanced age.
Finally, Pengas et al. (2012) demonstrate that spatial navigation impairments in AD
relate to damage across a network, which offers complimentary lesion evidence to studies
in healthy volunteers for the neural basis of topographical memory. Critically, the
results emphasize that structures beyond the medial temporal lobe contribute to memory
impairment in AD, which argues against common models in which memory impairment in
AD is taken as a synonym for hippocampal degeneration.
The book concludes with a review of human aging and spatial navigation tasks by Gazova
et al. (2012). They suggest that such navigation tasks may be a useful tool for identifying
individuals who will go on to develop AD. Given the growing number of studies indicating
that damage to the medial temporal lobe (including the hippocampus) is associated
with wayfinding difficulties, Gazova et al. (2012) argue that the use of such spatial
tasks may help to identify AD early in its course.