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Published on: January 12, 2016
White matter microstructure among youth with perinatally acquired HIV is associated with disease severity
Kristina A Uban1, Megan M Herting, Paige L Williams
1aDepartment of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California bCenter for Biostatistics in AIDS Research, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts cFeinberg School of Medicine, Northwestern University, Chicago, Illinois dDepartment of Neurosciences, Division of Pediatric Neurology, University of California San Diego, La Jolla eKeck School of Medicine, University of Southern California, Los Angeles, California, USA.
Insights
Youth with perinatally acquired HIV (PHIV) show altered brain white matter structure linked to disease severity. These changes may explain cognitive deficits, particularly in working memory.
Area of Science:
- Neuroscience
- Pediatric HIV Research
- Brain Imaging
Background:
- Perinatally acquired HIV (PHIV) can impact brain development and cognitive function.
- Structural brain connectivity alterations may underlie neurocognitive deficits in PHIV.
Purpose of the Study:
- To investigate the association between HIV disease severity and structural brain connectivity in youth.
- To determine if altered brain connectivity mediates the relationship between HIV disease severity and cognitive deficits.
Main Methods:
- Diffusion tensor imaging and tractography were used to assess white matter microstructure in 40 PHIV youth and 314 controls.
- Mediation analyses examined the role of white matter alterations in linking disease severity to cognitive performance.
Main Results:
- PHIV youth exhibited reduced fractional anisotropy and increased diffusivity in white matter compared to controls.
- Greater past HIV disease severity correlated with microstructural changes in specific white matter tracts (e.g., right IFO, left uncinate).
- Reduced right inferior fronto-occipital fractional anisotropy partially mediated the association between peak viral load and lower working memory.
Conclusions:
- PHIV youth have an increased risk of white matter microstructure alterations compared to typically developing youth.
- These alterations are associated with past HIV disease severity.
- White matter changes may mediate the link between HIV disease and working memory deficits in youth.
Objectives:
We investigated whether HIV disease severity was associated with alterations in structural brain connectivity, and whether those alterations in turn were associated with cognitive deficits in youth with perinatally acquired HIV (PHIV).
Design:
PHIV youth (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) (mean age: 16 ± 2 years) were included to evaluate how current and past disease severity measures (recent/nadir CD4%; peak viral load) relate to white matter microstructure within PHIV youth. PHIV youth were compared with 314 controls from the Pediatric Imaging, Neurocognition and Genetics (PING) study.
Methods:
Diffusion tensor imaging and tractography were utilized to assess white matter microstructure. Mediation analyses were conducted to examine whether microstructure alterations contributed to relationships between higher disease severity and specific cognitive domains in PHIV youth.
Results:
Whole brain fractional anisotropy was reduced, but radial and mean diffusivity were increased in PHIV compared with control youth. Within PHIV youth, more severe past HIV disease was associated with reduced fractional anisotropy of the right inferior fronto-occipital (IFO) and left uncinate tracts; elevated mean diffusivity of the F minor; and increased streamlines comprising the left inferior longitudinal fasciculus (ILF). Associations of higher peak viral load with lower working memory performance were partly mediated by reductions in right IFO fractional anisotropy levels.
Conclusion:
Our findings suggest that PHIV youth have a higher risk of alterations in white matter microstructure than typically developing youth, and certain alterations are related to past disease severity. Further, white matter alterations potentially mediate associations between HIV disease and working memory.
