Novel Neuroimaging Methods to Understand How HIV Affects the Brain

Thompson, Paul M.; Jahanshad, Neda

doi:10.1007/s11904-015-0268-6

Cited by 31 publications

(21 citation statements)

References 57 publications

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“…Despite a growing body of studies, the patterns and spatial distribution of brain injury remains unclear 5 . For example, increased putamen volume was detected in HIV-infected individuals compared to an age- and education-matched HIV-uninfected group 6 , while other studies have reported decreased putamen volume 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era

Sanford

Cruz

Scott

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Cognitive impairment still occurs in a substantial subset of HIV-infected patients, despite effective viral suppression with highly active antiretroviral therapy (HAART). Structural brain changes may provide clues about the underlying pathophysiology. This study provides a detailed spatial characterization of the pattern and extent of brain volume changes associated with HIV, and relates these brain measures to cognitive ability and clinical variables. Methods Multiple novel neuroimaging techniques (deformation-based morphometry, voxel-based morphometry and cortical modeling) were used to assess regional brain volumes in 125 HIV-infected patients and 62 HIV-uninfected individuals. 90% of the HIV-infected patients were on stable HAART with a majority (75%) having plasma viral suppression. Brain volumetrics and cortical thickness estimates were compared between the HIV-infected and uninfected groups, and the relationships between these measures of brain volume and indices of current and past infection severity, central nervous system penetration of HAART, and cognitive performance were assessed. Results Regionally specific patterns of reduced thalamic and brainstem volumes, as well as reduced cortical thickness in the orbitofrontal cortex, cingulate gyrus, primary motor and sensory cortex, temporal, and frontal lobes were seen in HIV-infected patients compared to HIV-uninfected participants. Observed white matter loss and subcortical atrophy were associated with lower nadir CD4 cell counts, while reduction in cortical thickness was related to worse cognitive performance. Conclusion Our findings suggest that distinct mechanisms may underlie cortical and subcortical injury in people with HIV, and argues for the potential importance of early initiation of HAART to protect long term brain health.

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Section: Introductionmentioning

confidence: 99%

Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era

Sanford

Cruz

Scott

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Prior neuroimaging studies in adults with HIV have reported that HIV severity was related to reduced global and regional brain volumes in both untreated patients and those treated with cART (Ances et al, 2012; Archibald et al, 2004; Becker et al, 2012, 2011; Cohen et al, 2010b; Heindel et al, 1994; Jernigan et al, 1993; Kallianpur et al, 2013; Stout, 1998; Thompson et al, 2005; Thompson and Jahanshad, 2015). Findings on cortical changes varied but overlapped between studies.…”

Section: Discussionmentioning

confidence: 99%

“…Studies including neuroimaging combined with cognitive evaluation allow for an in vivo characterization of how HIV and cART may mediate brain development (Thompson and Jahanshad, 2015). In adults, studies of post-mortem tissue and in vivo neuroimaging combined with cognitive testing have revealed atrophy in cortical and subcortical structures that is related to HIV severity and cognitive performance (Ances et al, 2012; Archibald et al, 2004; Becker et al, 2012, 2011; Cohen et al, 2010a; Heindel et al, 1994; Jernigan et al, 1993; Kallianpur et al, 2013; Stout, 1998; Thompson et al, 2005; Thompson and Jahanshad, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…In adults, studies of post-mortem tissue and in vivo neuroimaging combined with cognitive testing have revealed atrophy in cortical and subcortical structures that is related to HIV severity and cognitive performance (Ances et al, 2012; Archibald et al, 2004; Becker et al, 2012, 2011; Cohen et al, 2010a; Heindel et al, 1994; Jernigan et al, 1993; Kallianpur et al, 2013; Stout, 1998; Thompson et al, 2005; Thompson and Jahanshad, 2015). Still, the effects of early HIV infection on the underlying brain in adolescents with PHIV have not been well-characterized (Cohen et al, 2015; Hoare et al, 2014; Musielak and Fine, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Lower total and regional grey matter brain volumes in youth with perinatally-acquired HIV infection: Associations with HIV disease severity, substance use, and cognition

Angeles

Williams

Huo

et al. 2017

Brain, Behavior, and Immunity

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Despite improved survival due to combination antiretroviral therapy (cART), youth with perinatally-acquired HIV (PHIV) show cognitive deficits and developmental delay at increased rates. HIV affects the brain during critical periods of development, and the brain may be a persistent reservoir for HIV due to suboptimal blood brain barrier penetration of cART. We conducted structural magnetic resonance imaging (sMRI) and cognitive testing in 40 PHIV youth (mean age=16.7 years) recruited from the NIH Pediatric HIV/AIDS Cohort Study (PHACS) who are part of the first generation of PHIV youth surviving into adulthood. Historical and current HIV disease severity and substance use measures were also collected. Total and regional cortical grey matter brain volumes were compared to a group of 334 typically-developing, HIV-unexposed and uninfected youth (frequency-matched for age and sex) from the Pediatric Imaging, Neurocognition, and Genetics (PING) study (mean age=16.1 years). PHIV youth had smaller (2.8 – 5.1%) total and regional grey matter volumes than HIV-unexposed and uninfected youth, with smallest volumes seen among PHIV youth with higher past peak viral load (VL) and recent unsuppressed VL. In PHIV youth, worse cognitive performance correlated with smaller volumes. This pattern of smaller grey matter volumes suggests that PHIV infection may influence brain development and underlie cognitive dysfunction seen in this population. Among PHIV youth, smaller volumes were also linked to substance use (alcohol use: 9.0 – 13.4%; marijuana use: 10.1 – 16.0%). In this study, collection of substance use information was limited to the PHIV cohort; future studies should also collect substance use information in controls to further address interactions between HIV and substance use on brain volume.

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“…In fact, neuroimaging has contributed significantly to defining the neurologic manifestations of HIV-1 infection since the onset of the AIDS pandemic; neuroimaging remains invaluable in distinguishing lesions due to opportunistic CNS disease. Computerized tomography (CT) and magnetic resonance imaging (MRI) were utilized early in the HIV epidemic to detect encephalitis and damage to white matter (WM) (Thompson and Jahanshad, 2015). These earlier studies found that WM and caudate loss was accompanied with a larger CNS space in HIV patients (Stout et al , 1998).…”

Section: Neuroimaging Biomarkers For Hiv/neuroaidsmentioning

confidence: 99%

HIV/neuroAIDS biomarkers

Rahimian

2017

Progress in Neurobiology

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HIV infection often causes neurological symptoms including cognitive and motor dysfunction, which have been collectively termed HIV/neuroAIDS. Neuropsychological assessment and clinical symptoms have been the primary diagnostic criteria for HIV/neuroAIDS, even for the mild cognitive and motor disorder, the most prevalent form of HIV/neuroAIDS in the era of combination antiretroviral therapy. Those performance-based assessments and symptoms are generally descriptive and do not have the sensitivity and specificity to monitor the diagnosis, progression, and treatment response of the disease when compared to objective and quantitative laboratory-based biological markers, or biomarkers. In addition, effects of demographics and comorbidities such as substance abuse, psychiatric disease, nutritional deficiencies, and co-infection on HIV/neuroAIDS could be more readily determined using biomarkers than using neuropsychological assessment and clinical symptoms. Thus, there have been great efforts in identification of HIV/neuroAIDS biomarkers over the past two decades. The need for reliable biomarkers of HIV/neuroAIDS is expected to increase as the HIV-infected population ages and their vulnerability to neurodegenerative diseases, particularly Alzheimer’s disease increases. Currently, three classes of HIV/neuroAIDS biomarkers are being pursued to establish objective laboratory-based definitions of HIV-associated neurologic injury: cerebrospinal fluid biomarkers, blood biomarkers, and neuroimaging biomarkers. In this review, we will focus on the current knowledge in the field of HIV/neuroAIDS biomarker discovery.

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Novel Neuroimaging Methods to Understand How HIV Affects the Brain

Cited by 31 publications

References 57 publications

Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era

Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era

Lower total and regional grey matter brain volumes in youth with perinatally-acquired HIV infection: Associations with HIV disease severity, substance use, and cognition

HIV/neuroAIDS biomarkers

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