Cortical brain atrophy and intra-individual variability in neuropsychological test performance in HIV disease
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To characterize the relationship between dispersion-based intra-individual variability (IIVd) in neuropsychological test performance and brain volume among HIV seropositive and seronegative men and to determine the effects of cardiovascular risk and HIV infection on this relationship. Magnetic Resonance Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative controls (HIV-) in this cross-sectional cohort study. Voxel Based Morphometry was used to derive volumetric measurements at the level of the individual voxel. These brain structure maps were analyzed using Statistical Parametric Mapping (SPM2). IIVd was measured by computing intra-individual standard deviations (ISD’s) from the standardized performance scores of five neuropsychological tests: Wechsler Memory Scale-III Visual Reproduction I and II, Logical Memory I and II, Wechsler Adult Intelligence Scale-III Letter Number Sequencing. Total gray matter (GM) volume was inversely associated with IIVd. Among all subjects, IIVd -related GM atrophy was observed primarily in: 1) the inferior frontal gyrus bilaterally, the left inferior temporal gyrus extending to the supramarginal gyrus, spanning the lateral sulcus; 2) the right superior parietal lobule and intraparietal sulcus; and, 3) dorsal/ventral regions of the posterior section of the transverse temporal gyrus. HIV status, biological, and cardiovascular disease (CVD) variables were not linked to IIVd -related GM atrophy. IIVd in neuropsychological test performance may be a sensitive marker of cortical integrity in older adults, regardless of HIV infection status or CVD risk factors, and degree of intra-individual variability links with volume loss in specific cortical regions; independent of mean-level performance on neuropsychological tests.
KeywordsImaging Cognition HIV Voxel-based morphometry Intra-individual variability
The authors are grateful to the volunteers and the staff of the Multicenter AIDS Cohort Study for the time and effort that they contributed towards the successful completion of this project.
Compliance with ethical standards
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), Barbara Crain, Adrian Dobs, Homayoon Farzadegan, Joel Gallant, Lisette Johnson-Hill, Cynthia Munro, Michael W. Plankey, Ned Sacktor, James Shepard, Chloe Thio; Chicago (U01-AI35039): Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services: Steven M. Wolinsky (PI), John P. Phair, Sheila Badri, Maurice O’Gorman, David Ostrow, Frank Palella, Ann Ragin; Los Angeles (U01-AI35040): University of California, UCLA Schools of Public Health and Medicine: Roger Detels (PI), Otoniel Martínez-Maza (Co-PI), Aaron Aronow, Robert Bolan, Elizabeth Breen, Anthony Butch, Beth Jamieson, Eric N. Miller, 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), Lawrence A. Kingsley (Co-PI), James T. Becker, Ross D. Cranston, Jeremy J. Martinson, John W. Mellors, Anthony J. Silvestre, Ronald D. Stall; and the Data Coordinating Center (UM1-AI35043): The Johns Hopkins University Bloomberg School of Public Health: Lisa P. Jacobson (PI), Alvaro Munoz (Co-PI), Alison, Abraham, Keri Althoff, Christopher Cox, Jennifer Deal, Gypsyamber D’Souza, Priya Duggal, Janet Schollenberger, Eric C. Seaberg, Sol Su, Pamela Surkan. 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). 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-TR000424 (JHU CTSA). Website located at http://www.statepi.jhsph.edu/macs/macs.html. 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).
Additional grant funding
Additional funding for this work was provided by the UCLA CFAR grant 5P30 AI028697, T32-MH019535, from the Department of Veteran Affairs (VA Merit Review), and from the National Institute on Aging (AG034852 to JTB).
Conflict of interest
All authors have declared that he or she has no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
The data were analyzed by L.J. Hines, J.T. Becker and V. Maruca, with assistance from J. Sanders.
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