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Platelet decline as a predictor of brain injury in HIV infection

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Abstract

An association between platelet decline and increased risk of progression to dementia has been observed in an advanced HIV infection cohort study. This investigation evaluated the prognostic significance of platelet decline for dementia, for psychomotor slowing, and for brain injury, as quantified in vivo, in a much larger population of HIV+ men. Platelet counts and neurocognitive data were available from biannual visits of 2,125 HIV+ men participating in the prospective, Multicenter AIDS Cohort Study from 1984 to 2009. Brain volumetric data were also available from an imaging substudy of 83 seropositive participants aged 50 and older. The association of platelet counts with neurocognitive outcome was assessed using Cox proportional hazard models where change in platelet count from baseline was a time-updated variable. Marked platelet decline was associated with increased risk of dementia in univariate analysis (hazard ratio [HR] = 2.5, 95% confidence interval [CI] = 1.8–3.5), but not after adjustment for CD4 cell count, HIV viral load, age, study site, hemoglobin, race, education, smoking, and alcohol use (HR = 1.4, 95% CI = 0.78–2.5). Platelet decline did not predict psychomotor slowing in either univariate (HR = 0.79, 95% CI = 0.58–1.08) or multivariate (HR = 1.10, 95% CI = 0.73–1.67) analysis. Analysis of brain volumetric data, however, indicated a relationship between platelet decline and reduced gray matter volume fraction in univariate (p = 0.06) and multivariate (p < 0.05) analyses. Platelet decline was not an independent predictor of dementia or psychomotor slowing, after adjusting for stage of disease. Findings from a structural brain imaging substudy of older participants, however, support a possible relationship between platelet decline and reduced gray matter.

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Acknowledgments

The authors are grateful to the volunteers and the staff of the Multicenter AIDS Cohort Study for the time and effort contributed to the successful completion of this project. This study was supported in part by funds from the National Institute for Allergy and Infectious Diseases to the collaborating MACS sites: UO1-AI-35042, 5-MO1-RR-00052 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041 and by the National Institute of Mental Health: R01- MH-80636 (AR). The corresponding author, Ann Ragin, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Ann B. Ragin

  2. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Gypsyamber D’Souza & Sandra Reynolds

  3. Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA

    Eric Miller

  4. The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Ned Sacktor & Ola A. Selnes

  5. University of Illinois at Chicago, Chicago, IL, USA

    Eileen Martin

  6. School of Public Health, University of California Los Angeles, Los Angeles, CA, USA

    Barbara R. Visscher

  7. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    James T. Becker

  8. Department of Radiology, Northwestern University, 737 N. Michigan Avenue, Suite 1600, Chicago, IL, 60611, USA

    Ann B. Ragin

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  1. Ann B. Ragin
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Correspondence to Ann B. Ragin.

Additional information

The Neuropsychology Working Group of the Multicenter AIDS Cohort Study includes: Eric Miller, Ph.D.; Aaron Aaronow, M.D.; Barbara R. Visscher, M.D., Dr. P.H.; Bruce Cohen, M.D.; Eileen Martin, Ph.D.; Ann Ragin, Ph.D.; Ola A. Selnes, Ph.D.; Ned Sacktor, M.D.; and James T. Becker, Ph.D. The Multicenter AIDS Cohort Study (MACS) includes the following: Baltimore: The Johns Hopkins University Bloomberg School of Public Health: Joseph B. Margolick (Principal Investigator), Michael Plankey (Co-Principal Investigator), Barbara Crain, Adrian Dobs, Homayoon Farzadegan, Joel Gallant, Lisette Johnson-Hill, Ned Sacktor, Ola Selnes, James Shepard, Chloe Thio. Chicago: Howard Brown Health Center, Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services: John P. Phair (Principal Investigator), Steven M. Wolinsky (Principal Investigator), Sheila Badri, Craig Conover, Maurice O’Gorman, David Ostrow, Frank Palella, Ann Ragin. Los Angeles: University of California, UCLA Schools of Public Health and Medicine: Roger Detels (Principal Investigator), Otoniel Martínez-Maza (Co-Principal Investigator), Aaron Aronow, Robert Bolan, Elizabeth Breen, Anthony Butch, John Fahey, Beth Jamieson, Eric N. Miller, John Oishi, Harry Vinters, Barbara R. Visscher, Dorothy Wiley, Mallory Witt, Otto Yang, Stephen Young, Zuo Feng Zhang. Pittsburgh: University of Pittsburgh, Graduate School of Public Health: Charles R. Rinaldo (Principal Investigator), Lawrence A. Kingsley (Co-Principal Investigator), James T. Becker, Ross D. Cranston, Jeremy J. Martinson, John W. Mellors, Anthony J. Silvestre, Ronald D. Stall. Data Coordinating Center: The Johns Hopkins University Bloomberg School of Public Health: Lisa P. Jacobson (Principal Investigator), Alvaro Muoz (Co-Principal Investigator), Alison, Abraham, Keri Althoff, Christopher Cox, Gypsyanber D’Souza, Stephen J. Gange, Elizabeth Golub, Janet Schollenberger, Eric C. Seaberg, Sol Su. NIH: National Institute of Allergy and Infectious Diseases: Robin E. Huebner; National Cancer Institute: Geraldina Dominguez.

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Ragin, A.B., D’Souza, G., Reynolds, S. et al. Platelet decline as a predictor of brain injury in HIV infection. J. Neurovirol. 17, 487–495 (2011). https://doi.org/10.1007/s13365-011-0053-2

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