Relationship between neural functional connectivity and memory performance in age-related macular degeneration.

Abstract

Age-related macular degeneration (AMD) has been linked to memory deficits, with no established neural mechanisms. We collected resting-state brain functional magnetic resonance imaging and standardized verbal recall tests from 42 older adults with AMD and 41 age-matched controls. We used seed-based whole brain analysis to quantify the strength of functional connectivity between hubs of the default mode network and a network of medial temporal regions relevant for memory. Our results indicated neither memory performance nor network connectivity differed by AMD status. However, the AMD participants exhibited stronger relationships than the controls between memory performance and connectivity from the memory network hub (left parahippocampal) to 2 other regions: the left temporal pole and the right superior/middle frontal gyri. Also, the connectivity between the medial prefrontal cortex and posterior cingulate cortex of default mode network correlated more strongly with memory performance in AMD compared to control. We concluded that stronger brain-behavior correlation in AMD may suggest a role for region-specific connectivity in supporting memory in the context of AMD.

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Citation

Published Version (Please cite this version)

10.1016/j.neurobiolaging.2020.07.020

Publication Info

Zuo, Xintong, Jie Zhuang, Nan-Kuei Chen, Scott Cousins, Priscila Cunha, Eleonora M Lad, David J Madden, Guy Potter, et al. (2020). Relationship between neural functional connectivity and memory performance in age-related macular degeneration. Neurobiology of aging, 95. pp. 176–185. 10.1016/j.neurobiolaging.2020.07.020 Retrieved from https://hdl.handle.net/10161/22531.

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Scholars@Duke

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.

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.


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