Scott D. Moffat

Age differences in virtual environment and real world path integration

Accurate path integration (PI) requires the integration of visual, proprioceptive, and vestibular self-motion cues and age effects associated with alterations in processing information from these systems may contribute to declines in PI abilities. The present study investigated age-related differences in PI in conditions that varied as a function of available sources of sensory information. Twenty-two healthy, young (23.8 ± 3.0 years) and 16 older (70.1 ± 6.4 years) adults participated in distance reproduction and triangle completion tasks (TCTs) performed in a virtual environment (VE) and two “real world” conditions: guided walking and wheelchair propulsion. For walking and wheelchair propulsion conditions, participants wore a blindfold and wore noise-blocking headphones and were guided through the workspace by the experimenter. For the VE condition, participants viewed self-motion information on a computer monitor and used a joystick to navigate through the environment. For TCTs, older compared to younger individuals showed greater errors in rotation estimations performed in the wheelchair condition, and for rotation and distance estimations in the VE condition. Distance reproduction tasks (DRTs), in contrast, did not show any age effects. These findings demonstrate that age differences in PI vary as a function of the available sources of information and by the complexity of outbound pathway.

Contributions of sex, testosterone, and androgen receptor CAG repeat number to virtual Morris water maze performance.

The possibility that androgens contribute to the male advantage typically found on measures of spatial cognition has been investigated using a variety of approaches. To date, evidence to support the notion that androgens affect spatial cognition in healthy young adults is somewhat equivocal. The present study sought to clarify the association between testosterone (T) and spatial performance by extending measurements of androgenicity to include both measures of circulating T as well as an androgen receptor-specific genetic marker. The aims of this study were to assess the contributions of sex, T, and androgen receptor CAG repeat number (CAGr) on virtual Morris water task (vMWT) performance in a group of healthy young men and women. The hypothesis that men would outperform women on vMWT outcomes was supported. Results indicate that CAGr may interact with T to impact navigation performance and suggest that consideration of androgen receptor sensitivity is an important consideration in evaluating hormone-behavior relationships.

Long-term cortisol measures predict Alzheimer disease risk

Objective: To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk. Method: We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. Participants were from the Baltimore Longitudinal Study of Aging (BLSA) and submitted multiple 24-hour urine samples over an average interval of 10.56 years. Urinary free cortisol (UFC) and creatinine (Cr) were measured, and a UFC/Cr ratio was calculated to standardize UFC. To measure cortisol regulation, we used within-person UFC/Cr level (i.e., within-person mean), change in UFC/Cr over time (i.e., within-person slope), and UFC/Cr variability (i.e., within-person coefficient of variation). Cox regression was used to assess whether UFC/Cr measures predicted AD risk. Results: UFC/Cr level and UFC/Cr variability, but not UFC/Cr slope, were significant predictors of AD risk an average of 2.9 years before AD onset. Elevated UFC/Cr level and elevated UFC/Cr variability were related to a 1.31- and 1.38-times increase in AD risk, respectively. In a sensitivity analysis, increased UFC/Cr level and increased UFC/Cr variability predicted increased AD risk an average of 6 years before AD onset. Conclusions: Cortisol dysregulation as manifested by high UFC/Cr level and high UFC/Cr variability may modulate the downstream clinical expression of AD pathology or be a preclinical marker of AD.

Age-Related Differences in Associative Learning of Landmarks and Heading Directions in a Virtual Navigation Task

Previous studies have showed that spatial memory declines with age but have not clarified the relevance of different landmark cues for specifying heading directions among different age groups. This study examined differences between younger, middle-aged and older adults in route learning and memory tasks after they navigated a virtual maze that contained: (a) critical landmarks that were located at decision points (i.e., intersections) and (b) non-critical landmarks that were located at non-decision points (i.e., the sides of the route). Participants were given a recognition memory test for critical and non-critical landmarks and also given a landmark-direction associative learning task. Compared to younger adults, older adults committed more navigation errors during route learning and were poorer at associating the correct heading directions with both critical and non-critical landmarks. Notably, older adults exhibited a landmark-direction associative memory deficit at decision points; this was the first finding to show that an associative memory deficit exist among older adults in a navigational context for landmarks that are pertinent for reaching a goal, and suggest that older adults may expend more cognitive resources on the encoding of landmark/object features than on the binding of landmark and directional information. This study is also the first to show that older adults did not have a tendency to process non-critical landmarks, which were regarded as distractors/irrelevant cues for specifying the directions to reach the goal, to an equivalent or larger extent than younger adults. We explain this finding in view of the low number of non-critical cues in our virtual maze (relative to a real-world urban environment) that might not have evoked older adults’ usual tendency toward processing or encoding distractors. We explain the age differences in navigational and cognitive performance with regards to functional and structural changes in the hippocampus and parahippocampus, and recommend further investigations into the functional connectivity between the prefrontal cortex and hippocampus for a better understanding of the landmark-direction associative learning among the elderly. Finally, it is hoped that the current behavioral findings will facilitate efforts to identify the neural markers of Alzheimer’s disease, a disease that commonly involves navigational deficits.

Computerized cognitive training during physical inactivity improves executive functioning in older adults

ABSTRACT The hippocampus is closely tied to spatial navigation, a central component in cognitive functioning, and critically involved in age-associated cognitive decline and dementia. This study evaluated a novel, cognitive computerized spatial navigation training (CSNT) program targeting the hippocampus, with expectation of mitigating possible cognitive decline with bed rest (BR). During a 14-day BR study with 16 healthy, older men (mean age = 60 ± 3, range = 55–65 years), half received CSNT for 12 days in 50-min sessions and half were controls (watching documentaries). This design uniquely controlled diet, sleep, and other personal and environmental activities. Although there were no cognitive declines in controls post-BR, CSNT participants demonstrated significant increases in executive/attention ability and processing speed, and continued spatial navigation testing showed improvement to 400 days post-BR. This intervention may prove useful to mitigate cognitive declines known to occur in long periods of immobilization and could have broader implications in protecting against age-related cognitive decline.

Vestibular loss in older adults is associated with impaired spatial navigation: Data from the triangle completion task

Background Vestibular inputs have been shown to play a critical role in spatial navigation. In this study, we sought to evaluate whether vestibular loss due to aging contributes to impaired spatial navigation as measured by the triangle completion task (TCT). Materials and methods We recruited three types of participants: young controls <55 years of age, older controls ≥55 years of age, and older patients from a Neurotology Clinic with evidence of vestibular physiologic impairment but who did not have any known vestibular disorder. We performed the cervical vestibular-evoked myogenic potential to evaluate saccular function and video head impulse testing to quantify horizontal semicircular canal vestibulo-ocular reflex gain. To assess spatial navigation ability, we administered the TCT, in which participants were conveyed along two segments of a pre-drawn triangular path and instructed to complete the final segment independently. We measured the angle (degrees) and distance (centimeters) of deviation from the correct trajectory. We evaluated the influence of vestibular inputs on TCT performance. Results Forty-eight adults participated in the study (mean age: 62.0 years; 52.1% females), including 9 young controls, 15 older controls, and 24 clinic patients. Clinic patients had the greatest distance of deviation (67.7 cm), followed by older controls (45.4 cm), then young controls (27.8 cm; p < 0.01). Similarly, clinic patients had greater rotational angles (22.1°) compared to older (13.3°) and younger controls (12.4°; p < 0.01). Following multivariate linear regression adjusting for demographic variables, loss of otolith function was associated with an 18.2 cm increase in distance of deviation (95% CI: 15.2–47.4) and a 9.2° increase in rotational angle (95% CI: 3.0–15.5). Abnormal semicircular canal function was associated with a 26.0 cm increase in distance of deviation (95% CI: 0.2–51.8) and a 10.8° increase in rotational angle (95% CI: 3.0–15.5). Participants with both otolith and canal abnormalities had a larger distance error (β = 25.3, 95% CI: 6.2–44.4) and angle of deviation (β = 18.1, 95% CI: 10.1–26.2) than with either condition alone. Conclusion Vestibular loss in older adults was associated with poorer performance on a dynamic spatial navigation task relative to old and young controls.

The cortisol awakening response and cognition across the adult lifespan

Although the hippocampus is thought to play a central role in the regulation of the cortisol awakening response (CAR), results from past studies examining the relationship between the CAR and hippocampal-mediated memory and cognition have been mixed. Inconsistent findings may be due to the use of cortisol samples collected on only 1-2days since reduced sampling can permit unstable situational factors to bias results. We used cortisol assessments from 10 consecutive days to test the relationship of the CAR to episodic memory, working memory, and processing speed in a sample of healthy young, middle-aged, and older adults (age range: 23-79years; N=56). We tested if the relationship between the CAR and cognition would depend upon age and also tested if other cortisol measures, specifically waking cortisol, diurnal cortisol output (i.e., area under the curve) and diurnal cortisol slope (linear and quadratic), would be related to cognition. We found that a more positive CAR slope was related to better episodic memory and that this relationship did not depend upon age. The CAR was not significantly related to working memory. The relationship of the CAR to processing speed was not significant when using a CAR measure that corrected for non-compliant cortisol sampling. We also found that higher waking cortisol was significantly related to better working memory, but not episodic memory or processing speed. Neither diurnal cortisol output nor diurnal linear cortisol slope was significantly related to cognitive functioning. Future work should investigate the mechanisms underpinning the relationship of the cortisol awakening process to cognitive functioning.

Age-related similarities and differences in monitoring spatial cognition

ABSTRACT Spatial cognitive performance is impaired in later adulthood but it is unclear whether the metacognitive processes involved in monitoring spatial cognitive performance are also compromised. Inaccurate monitoring could affect whether people choose to engage in tasks that require spatial thinking and also the strategies they use in spatial domains such as navigation. The current experiment examined potential age differences in monitoring spatial cognitive performance in a variety of spatial domains including visual–spatial working memory, spatial orientation, spatial visualization, navigation, and place learning. Younger and older adults completed a 2D mental rotation test, 3D mental rotation test, paper folding test, spatial memory span test, two virtual navigation tasks, and a cognitive mapping test. Participants also made metacognitive judgments of performance (confidence judgments, judgments of learning, or navigation time estimates) on each trial for all spatial tasks. Preference for allocentric or egocentric navigation strategies was also measured. Overall, performance was poorer and confidence in performance was lower for older adults than younger adults. In most spatial domains, the absolute and relative accuracy of metacognitive judgments was equivalent for both age groups. However, age differences in monitoring accuracy (specifically relative accuracy) emerged in spatial tasks involving navigation. Confidence in navigating for a target location also mediated age differences in allocentric navigation strategy use. These findings suggest that with the possible exception of navigation monitoring, spatial cognition may be spared from age-related decline even though spatial cognition itself is impaired in older age.

The application of a rodent-based Morris water maze (MWM) protocol to an investigation of age-related differences in human spatial learning.

The current study applied a rodent-based Morris water maze (MWM) protocol to an investigation of search performance differences between young and older adult humans. To investigate whether similar age-related decline in search performance could be seen in humans based on the rodent-based protocol, we implemented a virtual MWM (vMWM) that has characteristics similar to those of the MWM used in previous studies of spatial learning in mice. Through the use of a proximity to platform measure, robust differences were found between healthy young and older adults in search performance. After dividing older adults into good and poor performers based on a median split of their corrected cumulative proximity values, the age effects in place learning were found to be largely related to search performance differences between the young and poor-performing older adults. When compared with the young, poor-performing older adults exhibited significantly higher proximity values in 83% of 24 place trials and overall in the probe trials that assessed spatial learning in the absence of the hidden platform. In contrast, good-performing older adults exhibited patterns of search performance that were comparable with that of the younger adults in most place and probe trials. Taken together, our findings suggest that the low search accuracy in poor-performing older adults stemmed from potential differences in strategy selection, differences in assumptions or expectations of task demands, as well as possible underlying functional and/or structural changes in the brain regions involved in vMWM search performance.

Cortisol Relates to Regional Limbic System Structure in Older but not Younger Adults

We investigated if the relationship between age and regional limbic system brain structure would be moderated by diurnal cortisol output and diurnal cortisol slope. Participants aged 23-83 years collected seven salivary cortisol samples each day for 10 consecutive days and underwent magnetic resonance imaging. Age, sex, cortisol, and an age x cortisol interaction were tested as predictors of hippocampal and amygdalar volume and caudal and rostral anterior cingulate cortex (ACC) thickness. We found significant interactions between age and cortisol on left and right amygdalar volumes and right caudal ACC thickness. Older adults with higher cortisol output had smaller left and right amygdalar volumes than older adults with lower cortisol output and younger adults with higher cortisol output. Older and younger adults with lower cortisol output had similar amygdalar volumes. Older adults with a steeper decline in diurnal cortisol had a thicker right caudal ACC than younger adults with a similarly shaped cortisol slope. Hippocampal volume was not related to either cortisol slope or output, nor was pallidum volume which was assessed as an extra-limbic control region. Results suggest that subtle differences in cortisol output are related to differences in limbic system structure in older but not younger adults.