White matter damage, neuroinflammation, and neuronal integrity in HAND.

TitleWhite matter damage, neuroinflammation, and neuronal integrity in HAND.
Publication TypeJournal Article
Year of Publication2019
AuthorsAlakkas, A, Ellis, RJ, Watson, CWei-Ming, Umlauf, A, Heaton, RK, Letendre, S, Collier, A, Marra, C, Clifford, DB, Gelman, B, Sacktor, N, Morgello, S, Simpson, D, J McCutchan, A, Kallianpur, A, Gianella, S, Marcotte, T, Grant, I, Fennema-Notestine, C
Corporate AuthorsCHARTER Group
JournalJ Neurovirol
Date Published2019 02
KeywordsAdult, AIDS Dementia Complex, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Aspartic Acid, Basal Ganglia, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Choline, Cognitive Dysfunction, Creatine, Female, Gray Matter, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Memory, Short-Term, Middle Aged, Neuroimaging, Neuropsychological Tests, Organ Size, Severity of Illness Index, White Matter

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds ratios were used to compare HAND to NU. Among 253 participants, 40% met HAND criteria (21% ANI, 15% MND, and 4% HAD). Higher risk of HAND was associated with more aWM. Both HAD and MND also had smaller gray and white matter volumes than NU. Among individuals with undetectable plasma HIV RNA, structural volumetric findings were similar to the overall sample. MND had lower FWM creatine and higher FGM choline relative to NU, whereas HAD and ANI had lower BG N-acetyl aspartate relative to NU. In the virologically suppressed subgroup, however, ANI and MND had higher FGM choline compared to NU. Overall, HAND showed specific alterations (more aWM and inflammation; less gray matter volume and lower NAA). Some MR measures differentiated less severe subtypes of HAND from HAD. These MR alterations may represent legacy effects or accumulating changes, possibly related to medical comorbidities, antiretroviral therapy, or chronic effects of HIV brain infection.

Alternate JournalJ Neurovirol
PubMed ID30291567
PubMed Central IDPMC6416232
Grant ListR21 HD094646 / HD / NICHD NIH HHS / United States
T32 DA031098 / DA / NIDA NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
[N01 MH2205 and HHSN271201000036C / / Foundation for the National Institutes of Health / International
R01 MH107345 / MH / NIMH NIH HHS / United States
P30 MH62512 / / Foundation for the National Institutes of Health / International
U24 MH100930 / MH / NIMH NIH HHS / United States