Cerebral white matter connectivity, cognition, and age-related macular degeneration.

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.

Department

Description

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Citation

Published Version (Please cite this version)

10.1016/j.nicl.2021.102594

Publication Info

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

Madden

David Joseph Madden

Professor in Psychiatry and Behavioral Sciences

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.

Badea

Alexandra Badea

Associate Professor in Radiology

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

Davis

Simon Wilton Davis

Associate Professor in Neurology

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? 

Cousins

Scott William Cousins

Robert Machemer, M.D. Distinguished Professor of Ophthalmology

Scott W. Cousins, M.D. is currently the Robert Machemer, M.D. Professor of Ophthalmology and Immunology, Vice Chair for Research, and Director of the Duke Center for Macular Diseases at Duke Eye Center. As Vice Chair, he oversees all basic science research as well as the Ophthalmology Site-Based Research Group, which administrates clinical research for Duke Eye Center. Dr. Cousins is also Medical Director of Hospital-Based Imaging and Procedures for Duke Eye Center.

Dr. Cousins is a retina-trained ophthalmologist who specializes in the diagnosis and treatment of macular diseases, especially age-related macular degeneration (AMD), diabetic retinopathy, and retinal vascular diseases. Dr. Cousins is active in both clinical and laboratory research. In his clinical practice, Dr. Cousins is involved in many trials and innovative therapies for the treatment of macular diseases, especially AMD and diabetic retinopathy. He has served as site PI for numerous phase1-3 clinical trials in AMD, diabetic retinopathy, and other retinal disorders. He has served as a consultant or member of data safety monitoring committees (DSMC) for numerous pharmaceutical and biotechnology startup companies.

In his scientific laboratory, Dr. Cousins pursues both NIH-funded and industry-funded research in various areas of dry and wet AMD. In particular, he is studying the role of circulating bone marrow-derived progenitors (stem cells) in contributing to wet AMD. His laboratory is attempting to develop treatments for dry macular degeneration and improving vision in eyes with wet macular degeneration. His program is also developing blood tests and new imaging technologies for the identification of patients who are at high risk for progressing into complications.

Dr. Cousins has published over 100 peer-reviewed manuscripts, book chapters, and other publications addressing topics of research or clinical care of retinal disease, especially AMD. In 2006, Dr. Cousins was awarded the prestigious Alcon Research Foundation Clinician Scientist Award. In 2008, the National Institutes of Health invited Dr. Cousins to join the National Advisory Eye Council. Dr. Cousins is also a member of the American Academy of Ophthalmology, the American Society of Retina Specialists, the Retina Society, the Association for Research in Vision and Ophthalmology, the American Association of Immunologists, and the American Medical Association.

In 2010, Dr. Cousins was named one of the “Top 34 Ophthalmologists in the United States” by Becker’s ASC Review, a leading source of business and legal news for ambulatory surgery centers. They cited his leadership of the Duke Center for Macular Diseases and his ongoing research in macular degeneration as reasons for the honor.

Whitson

Heather Elizabeth Whitson

Professor of Medicine

Dr. Whitson's research is focused on improving care options and resilience for people with multiple chronic conditions.  In particular, she has interest and expertise related to the link between age-related changes in the eye and brain (e.g., How does late-life vision loss impact the aging brain or cognitive outcomes?  Is Alzheimer's disease associated with distinctive changes in the retina, and could such changes help diagnose Alzheimer's disease early in its course?).  Dr. Whitson leads a collaborative Alzheimer's Disease initiative that brings together investigators from Duke University and the University of North Carolina (UNC) at Chapel Hill, with a bold vision to transform dementia research and care across Eastern North Carolina. Dr. Whitson is also interested in improving health services to better meet the needs of medically complex patients.  Within the Duke Aging Center, she leads research efforts aimed at promoting resilience to late-life stressors (e.g., surgery, sensory loss, infection).  She has developed a novel rehabilitation model for people with co-existing vision and cognitive deficits, and she is part of a inter-disciplinary team seeking to improve peri-operative outcomes for frail or at-risk seniors who must undergo surgery.  As a co-leader of a national resilience collaborative, she seeks to better understand the biological and psychological factors that determine how well we "bounce back" after health stressors.  


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