Effects of comorbidity burden and age on brain integrity in HIV.

TitleEffects of comorbidity burden and age on brain integrity in HIV.
Publication TypeJournal Article
Year of Publication2019
AuthorsSaloner, R, Heaton, RK, Campbell, LM, Chen, A, Franklin, D, Ellis, RJ, Collier, AC, Marra, C, Clifford, DB, Gelman, B, Sacktor, N, Morgello, S, J McCutchan, A, Letendre, S, Grant, I, Fennema-Notestine, C
Corporate AuthorsCHARTER Study Group
Date Published2019 06 01
KeywordsAdult, Aging, Anti-Retroviral Agents, Brain, Cohort Studies, Comorbidity, Cross-Sectional Studies, Female, Gray Matter, HIV, HIV Infections, Humans, Linear Models, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Middle Aged, Multivariate Analysis, Neuroimaging, Neuropsychological Tests, Sustained Virologic Response, White Matter

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.

Alternate JournalAIDS
PubMed ID30870195
PubMed Central IDPMC6613389
Grant ListK24 MH097673 / MH / NIMH NIH HHS / United States
HHSN271201000030C / MH / NIMH NIH HHS / United States
HHSN271201000036C / MH / NIMH NIH HHS / United States
T32 DA031098 / DA / NIDA NIH HHS / United States
T32 AA013525 / AA / NIAAA NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
N01 MH022005 / MH / NIMH NIH HHS / United States
R01 MH107345 / MH / NIMH NIH HHS / United States