Effects of Comorbidity Burden and Age on Brain Integrity in HIV

Overview

Journal AIDS

Specialty Infectious Diseases

Date 2019 Mar 15

PMID 30870195

Citations 27

Authors

Rowan Saloner

Robert K Heaton

Laura M Campbell

Anna Chen

Donald Franklin Jr

Ronald J Ellis

Ann C Collier

Christina Marra

David B Clifford

Benjamin Gelman

Ned Sacktor

Susan Morgello

J Allen McCutchan

Scott Letendre

Igor Grant

Christine Fennema-Notestine

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Predicting Trajectories of Everyday Functioning in Adults Aging with HIV Using Latent Growth Mixture Modeling.

Ham L, Roesch S, Franklin D, Ellis R, Grant I, Moore D AIDS Behav. 2025; .

PMID: 39928071 DOI: 10.1007/s10461-025-04623-z.

Latent Profile Analysis of Cognitive Performance and Depressive Symptoms Among People with HIV.

Kohli M, Ham L, Saloner R, Dung D, Iudicello J, Ellis R AIDS Patient Care STDS. 2024; 38(2):93-106.

PMID: 38381950 PMC: 10890962. DOI: 10.1089/apc.2023.0224.

Elevated Plasma Protein Carbonyl Concentration Is Associated with More Abnormal White Matter in People with HIV.

Riggs P, Anderson A, Tang B, Rubin L, Morgello S, Marra C Viruses. 2023; 15(12).

PMID: 38140650 PMC: 10747698. DOI: 10.3390/v15122410.

Use of different anticholinergic scales and their correlation with anticholinergic symptom burden in a cohort of people living with HIV.

Mazzitelli M, Trunfio M, Coin A, Sasset L, Farina J, Brundu M J Antimicrob Chemother. 2023; 79(1):66-77.

PMID: 37965917 PMC: 11032244. DOI: 10.1093/jac/dkad348.

Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management.

Ellis R, Marquine M, Kaul M, Fields J, Schlachetzki J Nat Rev Neurol. 2023; 19(11):668-687.

PMID: 37816937 PMC: 11052664. DOI: 10.1038/s41582-023-00879-y.

References

Anderson A, Fennema-Notestine C, Umlauf A, Taylor M, Clifford D, Marra C . CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease. J Neurovirol. 2015; 21(5):559-67. PMC: 5008689. DOI: 10.1007/s13365-015-0359-6. View

Wu M, Fatukasi O, Yang S, Alger J, Barker P, Hetherington H . HIV disease and diabetes interact to affect brain white matter hyperintensities and cognition. AIDS. 2018; 32(13):1803-1810. PMC: 6082131. DOI: 10.1097/QAD.0000000000001891. View

Provencher S . Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001; 14(4):260-4. DOI: 10.1002/nbm.698. View

Patel S, Thames A, Arbid N, Panos S, Castellon S, Hinkin C . The aggregate effects of multiple comorbid risk factors on cognition among HIV-infected individuals. J Clin Exp Neuropsychol. 2013; 35(4):421-34. PMC: 3641576. DOI: 10.1080/13803395.2013.783000. View

Cohen R, Harezlak J, Schifitto G, Hana G, Clark U, Gongvatana A . Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era. J Neurovirol. 2010; 16(1):25-32. PMC: 2995252. DOI: 10.3109/13550280903552420. View

Jernigan T, Archibald S, Fennema-Notestine C, Taylor M, Theilmann R, Julaton M . Clinical factors related to brain structure in HIV: the CHARTER study. J Neurovirol. 2011; 17(3):248-57. PMC: 3702821. DOI: 10.1007/s13365-011-0032-7. View

Pfefferbaum A, Rogosa D, Rosenbloom M, Chu W, Sassoon S, Kemper C . Accelerated aging of selective brain structures in human immunodeficiency virus infection: a controlled, longitudinal magnetic resonance imaging study. Neurobiol Aging. 2014; 35(7):1755-68. PMC: 3980003. DOI: 10.1016/j.neurobiolaging.2014.01.008. View

Marquine M, Montoya J, Umlauf A, Fazeli P, Gouaux B, Heaton R . The Veterans Aging Cohort Study (VACS) Index and Neurocognitive Change: A Longitudinal Study. Clin Infect Dis. 2016; 63(5):694-702. PMC: 4981756. DOI: 10.1093/cid/ciw328. View

Fowler J, Volkow N, Kassed C, Chang L . Imaging the addicted human brain. Sci Pract Perspect. 2007; 3(2):4-16. PMC: 2851068. DOI: 10.1151/spp07324. View

10.

Valcour V, Shikuma C, Shiramizu B, Watters M, Poff P, Selnes O . Higher frequency of dementia in older HIV-1 individuals: the Hawaii Aging with HIV-1 Cohort. Neurology. 2004; 63(5):822-7. PMC: 1382180. DOI: 10.1212/01.wnl.0000134665.58343.8d. View

11.

Garvey L, Pavese N, Ramlackhansingh A, Thomson E, Allsop J, Politis M . Acute HCV/HIV coinfection is associated with cognitive dysfunction and cerebral metabolite disturbance, but not increased microglial cell activation. PLoS One. 2012; 7(7):e38980. PMC: 3395624. DOI: 10.1371/journal.pone.0038980. View

12.

Masters M, Ances B . Role of neuroimaging in HIV-associated neurocognitive disorders. Semin Neurol. 2014; 34(1):89-102. PMC: 4217280. DOI: 10.1055/s-0034-1372346. View

13.

McCutchan J, Marquie-Beck J, Fitzsimons C, Letendre S, Ellis R, Heaton R . Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder. Neurology. 2012; 78(7):485-92. PMC: 3280051. DOI: 10.1212/WNL.0b013e3182478d64. View

14.

Fennema-Notestine C, McEvoy L, Notestine R, Panizzon M, Yau W, Franz C . White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure. Neuroimage Clin. 2016; 12:737-745. PMC: 5071546. DOI: 10.1016/j.nicl.2016.10.001. View

15.

Lin K, Taylor M, Heaton R, Franklin D, Jernigan T, Fennema-Notestine C . Effects of traumatic brain injury on cognitive functioning and cerebral metabolites in HIV-infected individuals. J Clin Exp Neuropsychol. 2011; 33(3):326-34. PMC: 3062232. DOI: 10.1080/13803395.2010.518140. View

16.

Heaton R, Franklin D, Ellis R, McCutchan J, Letendre S, LeBlanc S . HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2010; 17(1):3-16. PMC: 3032197. DOI: 10.1007/s13365-010-0006-1. View

17.

Clark K, Helland T, Specht K, Narr K, Manis F, Toga A . Neuroanatomical precursors of dyslexia identified from pre-reading through to age 11. Brain. 2014; 137(Pt 12):3136-41. PMC: 4240283. DOI: 10.1093/brain/awu229. View

18.

Fennema-Notestine C, Ellis R, Archibald S, Jernigan T, Letendre S, Notestine R . Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection. J Neurovirol. 2013; 19(4):393-401. PMC: 3776609. DOI: 10.1007/s13365-013-0185-7. View

19.

Fennema-Notestine C, Gamst A, Quinn B, Pacheco J, Jernigan T, Thal L . Feasibility of multi-site clinical structural neuroimaging studies of aging using legacy data. Neuroinformatics. 2007; 5(4):235-45. DOI: 10.1007/s12021-007-9003-9. View

20.

Tozzi V, Balestra P, Bellagamba R, Corpolongo A, Salvatori M, Visco-Comandini U . Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. J Acquir Immune Defic Syndr. 2007; 45(2):174-82. DOI: 10.1097/QAI.0b013e318042e1ee. View