TY - JOUR
T1 - Effects of comorbidity burden and age on brain integrity in HIV
AU - Saloner, Rowan
AU - Heaton, Robert K.
AU - Campbell, Laura M.
AU - Chen, Anna
AU - Franklin, Donald
AU - Ellis, Ronald J.
AU - Collier, Ann C.
AU - Marra, Christina
AU - Clifford, David B.
AU - Gelman, Benjamin
AU - Sacktor, Ned
AU - Morgello, Susan
AU - Allen McCutchan, J.
AU - Letendre, Scott
AU - Grant, Igor
AU - Fennema-Notestine, Christine
N1 - Funding Information:
C.M. receives royalties from UptoDate and Wolters Kluwer. This work was supported in part by awards from National Institutes of Health (the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) N01 MH2205 and HHSN271201000036C, to I.G.; R01 MH107345, to R.K.H. and S.L.; and P30 MH62512, to R.K.H.; T32AA013525 to R.S.; and T32DA031098 to L.M.C.). The views expressed in this article are those of the authors and do not reflect the official policy or position of the United States Government.
Funding Information:
The work was supported in part by awards from National Institutes of Health (the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) N01 MH2205 and HHSN271201000036C, to I.G.; R01 MH107345, to R.K.H. and S.L.; and P30 MH62512, to R.K.H.; T32AA013525 to R.S.; and T32DA031098 to L.M.C.). The views expressed in this article are those of the authors and do not reflect the official policy or position of the United States Government. We gratefully acknowledge all individuals who participated in CHARTER studies, as well as all CHARTER study investigators.
Funding Information:
The CNS HIV Anti-Retroviral Therapy Effects Research was supported by awards N01 MH22005, HHSN271201000036C, and HHSN271201000030C from the National Institutes of Health. The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) group is affiliated with Johns Hopkins University; the Icahn School of Medicine at Mount Sinai; University of California, San Diego; University of Texas, Galveston; University of Washington, Seattle; Washington University, St. Louis; and is headquartered at the University of California, San Diego and includes: Director: I.G., MD; Co-Directors: S.L., MD, R.J.E., MD, PhD, Thomas D. Marcotte, PhD; Center Manager: D.F.Jr.; Neuromedical Component: R.J.E., MD, PhD (PI), J. Allen McCutchan, MD; Laboratory and Virology Component: S.L., MD (Co-PI), Davey M. Smith, MD (Co-PI); Neurobehavioral Component: R.K.H., PhD (PI), J. Hampton Atkinson, MD, Matthew Dawson; Imaging Component: Christine Fennema-Notestine, PhD (PI), Michael J. Taylor, PhD, Rebecca Theilmann, PhD; Data Management Component: Anthony C. Gamst, PhD (PI), Clint Cushman; Statistics Component: Ian Abramson, PhD (PI), Florin Vaida, PhD; Johns Hopkins University Site: N.S. (PI), Vincent Rogalski; Icahn School of Medicine at Mount Sinai Site: S.M., MD (Co-PI) and David Simpson, MD (Co-PI), Letty Mintz, N.P.; University of California, San Diego Site: J. Allen McCutchan, MD (PI); University of Washington, Seattle Site: A.C.C., MD (Co-PI) and C.M., MD (Co-PI), Sher Storey, PA-C.; University of Texas, Galveston Site: B.G., MD, PhD (PI), Eleanor Head, RN, BSN; and Washington University, St. Louis Site: David Clifford, MD (PI), Muhammad Al-Lozi, MD, Mengesha Teshome, MD.
Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Objective:The influence of confounding neurocognitive comorbidities in people living with HIV (PLWH) on neuroimaging has not been systematically evaluated. We determined associations between comorbidity burden and brain integrity and examined the moderating effect of age on these relationships.Design:Observational, cross-sectional substudy of the CNS HIV Antiretroviral Therapy Effects Research cohort.Methods:A total of 288 PLWH (mean age = 44.2) underwent structural MRI and magnetic resonance spectroscopy as well as neurocognitive and neuromedical assessments. Consistent with Frascati criteria for HIV-associated neurocognitive disorders (HAND), neuromedical and neuropsychiatric comorbidity burden was classified as incidental (mild), contributing (moderate), or confounding (severe-exclusionary) to a diagnosis of HAND. Multiple regression modeling predicted neuroimaging outcomes as a function of comorbidity classification, age, and their interaction.Results:Comorbidity classifications were 176 incidental, 77 contributing, and 35 confounded; groups did not differ in HIV disease characteristics. Relative to incidental and contributing participants, confounded participants had less cortical gray matter and more abnormal white matter and ventricular cerebrospinal fluid, alongside more neuroinflammation (choline, myo-inositol) and less neuronal integrity (N-acetylaspartate). Older age exacerbated the impact of comorbidity burden: to a greater extent in the confounded group, older age was associated with more abnormal white matter (P = 0.017), less total white matter (P = 0.015), and less subcortical gray matter (P = 0.014).Conclusion:Neuroimaging in PLWH reveals signatures associated with confounding neurocognitive conditions, emphasizing the importance of evaluating these among individuals with suspected HAND. Older age amplifies subcortical and white matter tissue injury, especially in PLWH with severe comorbidity burden, warranting increased attention to this population as it ages.
AB - Objective:The influence of confounding neurocognitive comorbidities in people living with HIV (PLWH) on neuroimaging has not been systematically evaluated. We determined associations between comorbidity burden and brain integrity and examined the moderating effect of age on these relationships.Design:Observational, cross-sectional substudy of the CNS HIV Antiretroviral Therapy Effects Research cohort.Methods:A total of 288 PLWH (mean age = 44.2) underwent structural MRI and magnetic resonance spectroscopy as well as neurocognitive and neuromedical assessments. Consistent with Frascati criteria for HIV-associated neurocognitive disorders (HAND), neuromedical and neuropsychiatric comorbidity burden was classified as incidental (mild), contributing (moderate), or confounding (severe-exclusionary) to a diagnosis of HAND. Multiple regression modeling predicted neuroimaging outcomes as a function of comorbidity classification, age, and their interaction.Results:Comorbidity classifications were 176 incidental, 77 contributing, and 35 confounded; groups did not differ in HIV disease characteristics. Relative to incidental and contributing participants, confounded participants had less cortical gray matter and more abnormal white matter and ventricular cerebrospinal fluid, alongside more neuroinflammation (choline, myo-inositol) and less neuronal integrity (N-acetylaspartate). Older age exacerbated the impact of comorbidity burden: to a greater extent in the confounded group, older age was associated with more abnormal white matter (P = 0.017), less total white matter (P = 0.015), and less subcortical gray matter (P = 0.014).Conclusion:Neuroimaging in PLWH reveals signatures associated with confounding neurocognitive conditions, emphasizing the importance of evaluating these among individuals with suspected HAND. Older age amplifies subcortical and white matter tissue injury, especially in PLWH with severe comorbidity burden, warranting increased attention to this population as it ages.
KW - HIV
KW - MRI
KW - aging
KW - brain
KW - comorbidity
KW - magnetic resonance spectroscopy
KW - neurocognitive disorders
UR - http://www.scopus.com/inward/record.url?scp=85065510346&partnerID=8YFLogxK
U2 - 10.1097/QAD.0000000000002192
DO - 10.1097/QAD.0000000000002192
M3 - Article
C2 - 30870195
AN - SCOPUS:85065510346
SN - 0269-9370
VL - 33
SP - 1175
EP - 1185
JO - AIDS
JF - AIDS
IS - 7
ER -