Brain structural correlates of trajectories to cognitive impairment in men with and without HIV disease

Mikhail Popov; Samantha A. Molsberry; Fabrizio Lecci; Brian Junker; Lawrence A. Kingsley; Andrew Levine; Eileen Martin; Eric Miller; Cynthia A. Munro; Ann Ragin; Eric Seaberg; Ned Sacktor; James T. Becker

doi:10.1007/s11682-018-0026-7

Brain structural correlates of trajectories to cognitive impairment in men with and without HIV disease

Mikhail Popov, Samantha A. Molsberry, Fabrizio Lecci, Brian Junker, Lawrence A. Kingsley, Andrew Levine, Eileen Martin, Eric Miller, Cynthia A. Munro, Ann Ragin, Eric Seaberg, Ned Sacktor, James T. Becker^*

^*Corresponding author for this work

Radiology

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

There are distinct trajectories to cognitive impairment among participants in the Multicenter AIDS Cohort Study (MACS). Here we analyzed the relationship between regional brain volumes and the individual trajectories to impairment in a subsample (n = 302) of the cohort. 302 (167 HIV-infected; mean age = 55.7 yrs.; mean education: 16.2 yrs.) of the men enrolled in the MACS MRI study contributed data to this analysis. We used voxel-based morphometry (VBM) to segment the brain images to analyze gray and white matter volume at the voxel-level. A Mixed Membership Trajectory Model had previously identified three distinct profiles, and each study participant had a membership weight for each of these three trajectories. We estimated VBM model parameters for 100 imputations, manually performed the post-hoc contrasts, and pooled the results. We examined the associations between brain volume at the voxel level and the MMTM membership weights for two profiles: one considered “unhealthy” and the other considered “Premature aging.” The unhealthy profile was linked to the volume of the posterior cingulate gyrus/precuneus, the inferior frontal cortex, and the insula, whereas the premature aging profile was independently associated with the integrity of a portion of the precuneus. Trajectories to cognitive impairment are the result, in part, of atrophy in cortical regions linked to normal and pathological aging. These data suggest the possibility of predicting cognitive morbidity based on patterns of CNS atrophy.

Original language	English (US)
Pages (from-to)	821-829
Number of pages	9
Journal	Brain Imaging and Behavior
Volume	14
Issue number	3
DOIs	https://doi.org/10.1007/s11682-018-0026-7
State	Published - Jun 1 2020

Funding

The preparation of this manuscript and the collection of the MRI data were supported in part by funds from the NIH to J.T.B. (AG034852 and MH098745). Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS) with centers at Baltimore (U01-AI35042): The Johns Hopkins University Bloomberg School of Public Health: Joseph B. Margolick (PI), Jay Bream, Todd Brown, Adrian Dobs, Michelle Estrella, W. David Hardy, Lisette Johnson-Hill, Sean Leng, Anne Monroe, Cynthia Munro, Michael W. Plankey, Wendy Post, Ned Sacktor, Jennifer Schrack, Chloe Thio; Chicago (U01-AI35039): Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services: Steven M. Wolinsky (PI), Sheila Badri, Dana Gabuzda, Frank J. Palella, Jr., Sudhir Penugonda, John P. Phair, Susheel Reddy, Matthew Stephens, Linda Teplin; Los Angeles (U01-AI35040): University of California, UCLA Schools of Public Health and Medicine: Roger Detels (PI), Otoniel Martínez-Maza (PI), Peter Anton, Robert Bolan, Elizabeth Breen, Anthony Butch, Shehnaz Hussain, Beth Jamieson, John Oishi, Harry Vinters, Dorothy Wiley, Mallory Witt, Otto Yang, Stephen Young, Zuo Feng Zhang; Pittsburgh (U01-AI35041): University of Pittsburgh, Graduate School of Public Health: Charles R. Rinaldo (PI), James T. Becker, Phalguni Gupta, Kenneth Ho, Lawrence A. Kingsley, Susan Koletar, Jeremy J. Martinson, John W. Mellors, Anthony J. Silvestre, Ronald D. Stall; Data Coordinating Center (UM1-AI35043): The Johns Hopkins University Bloomberg School of Public Health: Lisa P. Jacobson (PI), Gypsyamber D’Souza (PI), Alison Abraham, Keri Althoff, Michael Collaco, Priya Duggal, Sabina Haberlen, Eithne Keelaghan, Heather McKay, Alvaro Muñoz, Derek Ng, Anne Rostich, Eric C. Seaberg, Sol Su, Pamela Surkan, Nicholas Wada. Institute of Allergy and Infectious Diseases: Robin E. Huebner; National Cancer Institute: Geraldina Dominguez. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR, or NCATS. The MACS website is located at http://aidscohortstudy.org/. The members of the Neuropsychology Working Group include Francine Barrington, James T. Becker, Pim Brouwers, Velpandi Ayyavoo, Karl Goodkin, Robin Huebner, Eithne Keelaghan, Andrew J. Levine, Eileen M. Martin, Cynthia Munro, Ann Ragin, Leah Rubin, Ned Sacktor, Eric Seaberg, and Carlie Williams.

Keywords

Brain structure
Dementia
HIV
Mixed membership trajectory
Multiple imputation

ASJC Scopus subject areas

Clinical Neurology
Neurology
Psychiatry and Mental health
Cellular and Molecular Neuroscience
Cognitive Neuroscience
Radiology Nuclear Medicine and imaging
Behavioral Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s11682-018-0026-7

Cite this

Popov, M., Molsberry, S. A., Lecci, F., Junker, B., Kingsley, L. A., Levine, A., Martin, E., Miller, E., Munro, C. A., Ragin, A., Seaberg, E., Sacktor, N., & Becker, J. T. (2020). Brain structural correlates of trajectories to cognitive impairment in men with and without HIV disease. Brain Imaging and Behavior, 14(3), 821-829. https://doi.org/10.1007/s11682-018-0026-7

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abstract = "There are distinct trajectories to cognitive impairment among participants in the Multicenter AIDS Cohort Study (MACS). Here we analyzed the relationship between regional brain volumes and the individual trajectories to impairment in a subsample (n = 302) of the cohort. 302 (167 HIV-infected; mean age = 55.7 yrs.; mean education: 16.2 yrs.) of the men enrolled in the MACS MRI study contributed data to this analysis. We used voxel-based morphometry (VBM) to segment the brain images to analyze gray and white matter volume at the voxel-level. A Mixed Membership Trajectory Model had previously identified three distinct profiles, and each study participant had a membership weight for each of these three trajectories. We estimated VBM model parameters for 100 imputations, manually performed the post-hoc contrasts, and pooled the results. We examined the associations between brain volume at the voxel level and the MMTM membership weights for two profiles: one considered “unhealthy” and the other considered “Premature aging.” The unhealthy profile was linked to the volume of the posterior cingulate gyrus/precuneus, the inferior frontal cortex, and the insula, whereas the premature aging profile was independently associated with the integrity of a portion of the precuneus. Trajectories to cognitive impairment are the result, in part, of atrophy in cortical regions linked to normal and pathological aging. These data suggest the possibility of predicting cognitive morbidity based on patterns of CNS atrophy.",

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AU - Popov, Mikhail

AU - Molsberry, Samantha A.

AU - Lecci, Fabrizio

AU - Junker, Brian

AU - Kingsley, Lawrence A.

AU - Levine, Andrew

AU - Martin, Eileen

AU - Miller, Eric

AU - Munro, Cynthia A.

AU - Ragin, Ann

AU - Seaberg, Eric

AU - Sacktor, Ned

AU - Becker, James T.

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N2 - There are distinct trajectories to cognitive impairment among participants in the Multicenter AIDS Cohort Study (MACS). Here we analyzed the relationship between regional brain volumes and the individual trajectories to impairment in a subsample (n = 302) of the cohort. 302 (167 HIV-infected; mean age = 55.7 yrs.; mean education: 16.2 yrs.) of the men enrolled in the MACS MRI study contributed data to this analysis. We used voxel-based morphometry (VBM) to segment the brain images to analyze gray and white matter volume at the voxel-level. A Mixed Membership Trajectory Model had previously identified three distinct profiles, and each study participant had a membership weight for each of these three trajectories. We estimated VBM model parameters for 100 imputations, manually performed the post-hoc contrasts, and pooled the results. We examined the associations between brain volume at the voxel level and the MMTM membership weights for two profiles: one considered “unhealthy” and the other considered “Premature aging.” The unhealthy profile was linked to the volume of the posterior cingulate gyrus/precuneus, the inferior frontal cortex, and the insula, whereas the premature aging profile was independently associated with the integrity of a portion of the precuneus. Trajectories to cognitive impairment are the result, in part, of atrophy in cortical regions linked to normal and pathological aging. These data suggest the possibility of predicting cognitive morbidity based on patterns of CNS atrophy.

AB - There are distinct trajectories to cognitive impairment among participants in the Multicenter AIDS Cohort Study (MACS). Here we analyzed the relationship between regional brain volumes and the individual trajectories to impairment in a subsample (n = 302) of the cohort. 302 (167 HIV-infected; mean age = 55.7 yrs.; mean education: 16.2 yrs.) of the men enrolled in the MACS MRI study contributed data to this analysis. We used voxel-based morphometry (VBM) to segment the brain images to analyze gray and white matter volume at the voxel-level. A Mixed Membership Trajectory Model had previously identified three distinct profiles, and each study participant had a membership weight for each of these three trajectories. We estimated VBM model parameters for 100 imputations, manually performed the post-hoc contrasts, and pooled the results. We examined the associations between brain volume at the voxel level and the MMTM membership weights for two profiles: one considered “unhealthy” and the other considered “Premature aging.” The unhealthy profile was linked to the volume of the posterior cingulate gyrus/precuneus, the inferior frontal cortex, and the insula, whereas the premature aging profile was independently associated with the integrity of a portion of the precuneus. Trajectories to cognitive impairment are the result, in part, of atrophy in cortical regions linked to normal and pathological aging. These data suggest the possibility of predicting cognitive morbidity based on patterns of CNS atrophy.

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Brain structural correlates of trajectories to cognitive impairment in men with and without HIV disease

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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