Cerebral white matter connectivity, cognition, and age-related macular degeneration.
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2021-02-23
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Abstract
Age-related macular degeneration (AMD) is a common retina disease associated with cognitive impairment in older adults. The mechanism(s) that account for the link between AMD and cognitive decline remain unclear. Here we aim to shed light on this issue by investigating whether relationships between cognition and white matter in the brain differ by AMD status. In a direct group comparison of brain connectometry maps from diffusion weighted images, AMD patients showed significantly weaker quantitative anisotropy (QA) than healthy controls, predominantly in the splenium and left optic radiation. The QA of these tracts, however, did not correlate with the visual acuity measure, indicating that this group effect is not directly driven by visual loss. The AMD and control groups did not differ significantly in cognitive performance.Across all participants, better cognitive performance (e.g. verbal fluency) is associated with stronger connectivity strength in white matter tracts including the splenium and the left inferior fronto-occipital fasciculus/inferior longitudinal fasciculus. However, there were significant interactions between group and cognitive performance (verbal fluency, memory), suggesting that the relation between QA and cognitive performance was weaker in AMD patients than in controls.This may be explained by unmeasured determinants of performance that are more common or impactful in AMD or by a recruitment bias whereby the AMD group had higher cognitive reserve. In general, our findings suggest that neural degeneration in the brain might occur in parallel to AMD in the eyes, although the participants studied here do not (yet) exhibit overt cognitive declines per standard assessments.
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Zhuang, Jie, David J Madden, Priscila Cunha, Alexandra Badea, Simon W Davis, Guy G Potter, Eleonora M Lad, Scott W Cousins, et al. (2021). Cerebral white matter connectivity, cognition, and age-related macular degeneration. NeuroImage. Clinical, 30. p. 102594. 10.1016/j.nicl.2021.102594 Retrieved from https://hdl.handle.net/10161/22525.
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Scholars@Duke
David Joseph Madden
My research focuses primarily on the cognitive neuroscience of aging: the investigation of age-related changes in perception, attention, and memory, using both behavioral measures and neuroimaging techniques, including positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI).
The behavioral measures have focused on reaction time, with the goal of distinguishing age-related changes in specific cognitive abilities from more general effects arising from a slowing in elementary perceptual processes. The cognitive abilities of interest include selective attention as measured in visual search tasks, semantic and episodic memory retrieval, and executive control processes.
The behavioral measures are necessary to define the cognitive abilities of interest, and the neuroimaging techniques help define the functional neuroanatomy of those abilities. The PET and fMRI measures provide information regarding neural activity during cognitive performance. DTI is a recently developed technique that images the structural integrity of white matter. The white matter tracts of the brain provide critical pathways linking the gray matter regions, and thus this work will complement the studies using PET and fMRI that focus on gray matter activation.
A current focus of the research program is the functional connectivity among regions, not only during cognitive task performance but also during rest. These latter measures, referred to as intrinsic functional connectivity, are beginning to show promise as an index of overall brain functional efficiency, which can be assessed without the implementation of a specific cognitive task. From DTI, information can be obtained regarding how anatomical connectivity constrains intrinsic functional connectivity. It will be important to determine the relative influence of white matter pathway integrity, intrinsic functional connectivity, and task-related functional connectivity, as mediators of age-related differences in behavioral measures of cognitive performance.
Ultimately, the research program can help link age-related changes in cognitive performance to changes in the structure and function of specific neural systems. The results also have implications for clinical translation, in terms of the identification of neural biomarkers for the diagnosis of neural pathology and targeting rehabilitation procedures.
Alexandra Badea
I have a joint appointment in Radiology and Neurology and my research focuses on neurological conditions like Alzheimer’s disease. I work on imaging and analysis to provide a comprehensive characterization of the brain. MRI is particularly suitable for brain imaging, and diffusion tensor imaging is an important tool for studying brain microstructure, and the connectivity amongst gray matter regions.
I am interested in image segmentation, morphometry and shape analysis, as well as in integrating information from MRI with genetics, and behavior. Our approaches target: 1) phenotyping the neuroanatomy using imaging; 2) uncovering the link between structural and functional changes, the genetic bases, and environmental factors. I am interested in generating methods and tools for comprehensive phenotyping.
We use high-performance cluster computing to accelerate our image analysis. We use compressed sensing image reconstruction, and process large image arrays using deformable registration, perform segmentation based on multiple image contrasts including diffusion tensor imaging, as well as voxel, and graph analysis for connectomics.
At BIAC my efforts focus on developing multivariate biomarkers and identifying vulnerable networks based on genetic risk for Alzheimer's disease.
My enthusiasm comes from the possibility to extend from single to integrative multivariate and network based analyses to obtain a comprehensive picture of normal development and aging, stages of disease, and the effects of treatments. I am working on multivariate image analysis and predictive modeling approaches to help better understand early biomarkers for human disease indirectly through mouse models, as well as directly in human studies.
I am dedicated to supporting an increase in female presence in STEM fields, and love working with students. The Bass Connections teams involve undergraduate students in research, providing them the opportunity to do independent research studies and get involved with the community. These students have for example takes classes such as:
BME 394: Projects in Biomedical Engineering (GE)
BME 493: Projects in Biomedical Engineering (GE)
ECE 899: Special Readings in Electrical Engineering
NEUROSCI 493: Research Independent Study 1
Simon Wilton Davis
My research centers around the use of structural and functional imaging measures to study the shifts in network architecture in the aging brain. I am specifically interested in changes in how changes in structural and functional connectivity associated with aging impact the semantic retrieval of word or fact knowledge. Currently this involves asking why older adults have particular difficulty in certain kinds of semantic retrieval, despite the fact that vocabularies and knowledge stores typically improve with age.
A second line of research involves asking questions about how this semantic system is organized in young adults, understanding which helps form a basis for asking questions about older adults. To what degree are these semantic retrieval processes lateralized? What cognitive factors affect this laterality? How are brain structures like the corpus callosum involved in mediating distributed activation patterns associated with semantic retrieval?
Guy Glenn Potter
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