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An Augmented Aging Process in Brain White Matter in HIV

T. Kuhn, T. Kaufmann, N.T. Doan, L.T. Westlye, J. Jones, R.A. Nunez, S.Y. Bookheimer, E.J. Singer, C.H. Hinkin, A.D. Thames
doi: https://doi.org/10.1101/265199
T. Kuhn
aDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles. 740 Westwood Plaza, C8-746 Los Angeles, CA 90073, United States
bVeterans Association Greater Los Angeles Healthcare Center. 11301 Wilshire Blvd, Los Angeles, CA 90049, United States
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T. Kaufmann
eNORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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N.T. Doan
eNORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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L.T. Westlye
eNORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
fDepartment of Psychology, University of Oslo, Oslo, Norway
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J. Jones
aDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles. 740 Westwood Plaza, C8-746 Los Angeles, CA 90073, United States
bVeterans Association Greater Los Angeles Healthcare Center. 11301 Wilshire Blvd, Los Angeles, CA 90049, United States
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R.A. Nunez
aDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles. 740 Westwood Plaza, C8-746 Los Angeles, CA 90073, United States
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S.Y. Bookheimer
aDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles. 740 Westwood Plaza, C8-746 Los Angeles, CA 90073, United States
cDepartment of Cognitive Psychology, Tennenbaum Center for the Biology of Creativity, University of California, Los Angeles. 635 Charles E Young Dr. S, 260-M Los Angeles, CA 90095, United States
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E.J. Singer
dDepartment of Neurology, University of California, Los Angeles. 710 Westwood Plaza Los Angeles, CA 90073, United States
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C.H. Hinkin
aDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles. 740 Westwood Plaza, C8-746 Los Angeles, CA 90073, United States
bVeterans Association Greater Los Angeles Healthcare Center. 11301 Wilshire Blvd, Los Angeles, CA 90049, United States
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A.D. Thames
aDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles. 740 Westwood Plaza, C8-746 Los Angeles, CA 90073, United States
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Abstract

Objective HIV infection and aging are both associated with neurodegeneration. However, whether the aging process alone or other factors associated with advanced age account for the progression of neurodegeneration in the aging HIV-positive (HIV+) population remains unclear.

Methods HIV+ (n=70) and HIV-negative (HIV-, n=34) participants underwent diffusion tensor imaging (DTI) and metrics of microstructural properties were extracted from regions of interest (ROIs). A support vector regression model was trained on two independent datasets of healthy adults across the adult life-span (n=765, Cam-CAN = 588; UiO = 177) to predict participant age from DTI metrics, and applied to the HIV dataset. Predicted brain age gap (BAG) was computed as the difference between predicted age and chronological age, and statistically compared between HIV groups. Regressions assessed the relationship between BAG and HIV severity/medical comorbidities. Finally, correlation analyses tested for associations between BAG and cognitive performance.

Results BAG was significantly higher in the HIV+ group than the HIV-group F (1, 103) = 12.408, p = 0.001). HIV RNA viral load was significantly associated with BAG, particularly in older HIV+ individuals (R2 = 0.29, F(7, 70) = 2.66, p = 0.021). Further, BAG was negatively correlated with domain-level cognitive function (learning: r = −0.26, p = 0.008; memory: r = −0.21, p = 0.034).

Conclusions HIV infection is associated with augmented white matter aging, and greater brain aging is associated with worse cognitive performance in multiple domains.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 22, 2018.
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An Augmented Aging Process in Brain White Matter in HIV
T. Kuhn, T. Kaufmann, N.T. Doan, L.T. Westlye, J. Jones, R.A. Nunez, S.Y. Bookheimer, E.J. Singer, C.H. Hinkin, A.D. Thames
bioRxiv 265199; doi: https://doi.org/10.1101/265199
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An Augmented Aging Process in Brain White Matter in HIV
T. Kuhn, T. Kaufmann, N.T. Doan, L.T. Westlye, J. Jones, R.A. Nunez, S.Y. Bookheimer, E.J. Singer, C.H. Hinkin, A.D. Thames
bioRxiv 265199; doi: https://doi.org/10.1101/265199

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