2017 — 2018 |
Head, Denise P |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Understanding the Return Journey: Route Reversal in Younger and Older Adults
PROJECT SUMMARY/ABSTRACT Age-related difficulties in spatial navigation pose a significant risk to older adults' independence, safety and confidence in travelling to new environments. Nonetheless, most of the existing literature documenting age effects on route learning has only examined traversing a route in one direction to a target location, which ignores that a route is often traveled both to and back from a destination. While limited research does indicate greater age-related deficits in route reversal than in repeating the route in the same direction, there is a gap in understanding the cognitive and neural determinants of route reversal performance in older adults. Thus, the proposed research will examine the influence of three targeted cognitive processes, as well as brain structures, on older adults' difficulty in route reversal. Learning a route in one direction involves development of a caudate- based egocentric representation of a series of body turns. However, route reversal may require a more flexible, hippocampal-dependent representation of the spatial relationships amongst features of the environment (i.e., an allocentric representation). In addition, route reversal may place greater demands upon the ability to mentally transform one's viewpoint (egocentric perspective taking). Knowledge of the reverse ordering of landmarks along the route (reverse temporal sequencing) could also be particularly relevant for route reversal. Both egocentric perspective taking and temporal sequencing are also in part associated with the hippocampus. Each of these abilities that may be particularly associated with route reversal evidence decline with advancing age, and the magnitude of hippocampal atrophy exceeds that of caudate atrophy. Thus, our underlying hypotheses are that a) greater contributions of an allocentric representation, egocentric perspective taking and reverse temporal sequencing to route reversal are determinants of greater age effects on reversal; and b) atrophy of the hippocampus contributes to differential age effects in route reversal. Across three experiments, younger and older adults will a) traverse a route to and from a target destination in virtual environments after learning the route using various methods, and b) complete independent measures of the targeted cognitive abilities. The proposed research will a) test the effectiveness of targeted interventions during learning in reducing age effects on route reversal; b) test the role of individual differences in the targeted cognitive abilities in age effects on route reversal; and c) test the role of MRI-based measures of hippocampus and caudate in age effects on route reversal. The proposed research will provide novel insights regarding the neural substrates of route reversal as well as factors that enhance route reversal ability in older adults. Identification of such factors will afford new opportunities for designing navigational aids targeting route presentation to improve this critical navigation skill in an aging population. Importantly, the investigation of route reversal in healthy aging can lead to insight into the earliest stages of Alzheimer's disease, which entails early atrophy of hippocampal circuits as well as allocentric navigation deficits in the preclinical phase.
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2021 |
Head, Denise P |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Mechanisms and Moderators of the Effects of Physical Activity in Preclinical Alzheimer Disease
Project 4: Project Summary/Abstract Physical activity is emerging as a potential non-pharmacological intervention to reduce the risk of developing symptomatic AD. However, there are several unresolved issues regarding the potential role of physical activity. First, the neurobiological mechanisms by which physical activity may be protective are unclear. While there is evidence from rodent studies that exercise-induced increase in trophic factors reduce AD pathology, enhance hippocampal neuroplasticity and improve hippocampal-dependent memory, this pathway has not been fully tested in humans. Second, there is limited understanding of the factors that contribute to individual differences in the effectiveness of physical activity. Third, the majority of studies have used self-report measures with variable evidence of reliability and validity, which could lead to biased estimation of effects. Lastly, the effect of physical activity on core AD pathology has been less examined with mixed findings in the literature. Project 4 will address these gaps and limitations by testing the mechanistic model supported by animal work in humans and determining factors that may moderate the beneficial effects of physical activity, both cross-sectionally and longitudinally. Aim 1 will test the hypothesis that higher levels of physical activity will be associated with benefits for neuronal/synaptic integrity and hence medial temporal lobe structure and episodic memory both directly by reduced amyloid deposition and tau phosphorylation (via increased trophic factors) and indirectly by mitigating the negative effects of AD pathology. Aim 2 will test the hypothesis that vascular health and the response of trophic factors to an acute bout of exercise moderate the effects of physical activity on AD biomarkers, medial temporal lobe structure and episodic memory. Exploratory Aim 3 will examine the role of stress exposure (Clinical Core) and reactivity, inflammation (Projects 1 & 2), and the gut microbiome (Project 3) in the effects of physical activity. Physical activity will be robustly characterized with objective measures of cardiorespiratory fitness and actigraphy-derived estimates of physical activity over 7 days. We will incorporate blood measures of trophic factors, CSF measures of neuronal integrity (Fluid Biomarker Core), structural MRI and DTI measures of medial temporal lobe structure (Project 1) as well as CSF and PET measures of AD biomarkers (Projects 1 & 2). Importantly, this Project represents a critical initial step in a line of research to determine the degree to which physical activity, directly and/or indirectly, influences the transition from cognitive normality to symptomatic AD.
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