White matter damage, neuroinflammation, and neuronal integrity in HAND

for the CHARTER Group

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 HIV­associated 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 N­acetyl 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.

Original languageEnglish (US)
JournalJournal of NeuroVirology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

HIV
Dementia
Magnetic Resonance Spectroscopy
Choline
Basal Ganglia
Comorbidity
Neurocognitive Disorders
White Matter
Creatine
Aspartic Acid
HIV Infections
Gray Matter
Odds Ratio
Magnetic Resonance Imaging
Cognitive Dysfunction
RNA
Inflammation
Brain
Therapeutics

Keywords

  • HAND
  • MRI

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

Cite this

White matter damage, neuroinflammation, and neuronal integrity in HAND. / for the CHARTER Group.

In: Journal of NeuroVirology, 01.01.2018.

Research output: Contribution to journalArticle

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title = "White matter damage, neuroinflammation, and neuronal integrity in HAND",
abstract = "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 HIV­associated 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 N­acetyl 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.",
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T1 - White matter damage, neuroinflammation, and neuronal integrity in HAND

AU - for the CHARTER Group

AU - Alakkas, Aljoharah

AU - Ellis, Ronald J.

AU - Watson, Caitlin Wei Ming

AU - Umlauf, Anya

AU - Heaton, Robert K.

AU - Letendre, Scott

AU - Collier, Ann

AU - Marra, Christina

AU - Clifford, David B.

AU - Gelman, Benjamin

AU - Sacktor, Ned

AU - Morgello, Susan

AU - Simpson, David

AU - McCutchan, J. Allen

AU - Kallianpur, Asha

AU - Gianella, Sara

AU - Marcotte, Thomas

AU - Grant, Igor

AU - Fennema-Notestine, Christine

PY - 2018/1/1

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